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The Pathology of Synapses in Brain Networks Implicated in Depression

Brain Imaging of Prefrontal-Limbic Networks Point to a Loss of Synapses in Depression
  • Maxwell Bennett
Chapter

Abstract

Non-invasive brain imaging has identified changes in the prefrontal–limbic network (Fig. 6.1) in patients suffering from major depression disease (MDD), principally in prefrontal cortex, anterior cingulate cortex, orbitofrontal cortex, hippocampus and the amygdala. For example, different regions in the medial prefrontal cortex and orbitofrontal cortex normally exert an inhibitory influence over activity in the amygdala, but fail to do so in depression according to functional magnetic resonance imaging (fMRI) studies (Drevets 2007; Savitz and Drevets 2009). Furthermore the evidence suggests there is a lack of functional connection in depressed patients between the subgenual anterior cingulate cortex (ACC) on the one hand and the rostral (pregenual) ACC and hippocampus on the other, as well as between the rostral ACC and the amygdala (Anand et al. 2009; Savitz and Drevets 2009). In depressed patients there is increased activity in the subgenual ACC accompanied by decreased activity in the dorsolateral prefrontal cortex (Drevets et al. 2008; Mayberg et al. 1999) leading to the conjecture that it is failure of inhibitory control from the dorsal areas over the ventral areas that leads to increased activity in the ventral areas (Taylor and Liberzon 2007). Use of multivariate techniques combined with structural equation modeling, applied to resting-state positron emission tomography (PET) scans of acutely depressed patients, show differences in known anatomical and physiological pathways. An estimate has been made of the strength and direction of ‘effective connections’ between these areas (James et al. 2009). Changes are observed between subgenual ACC, pregenual ACC, orbitofrontal cortex, hippocampus/amygdala, and the prefrontal cortex (Fig. 6.1).

Keywords

Grey Matter Anterior Cingulate Cortex Grey Matter Volume Orbitofrontal Cortex Cortical Grey Matter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Afadlal S, Polaboon N, Surakul P, Govitrapong P, Jutapakdeegul N (2010) Prenatal stress alters presynaptic marker proteins in the hippocampus of rat pups. Neurosci Lett 470:24–27PubMedCrossRefGoogle Scholar
  2. Aisa B, Elizalde N, Tordera R, Lasheras B, del Rio J, Ramirez MJ (2009) Effects of neonatal stress on markers of synaptic plasticity in the hippocampus: implications for spatial memory. Hippocampus 19:1222–1231PubMedCrossRefGoogle Scholar
  3. Anand A, Li Y, Wang Y, Lowe MJ, Dzemidzic M (2009) Resting state corticolimbic connectivity abnormalities in unmedicated bipolar disorder and unipolar depression. Psychiatry Res 171:189–198PubMedCrossRefGoogle Scholar
  4. Andersen SL, Teicher MH (2004) Delayed effects of early stress on hippocampal development. Neuropsychopharmacology 29:1988–1993PubMedCrossRefGoogle Scholar
  5. Anderson B, Rutledge V (1996) Age and hemisphere effects on dendritic structure. Brain 119(Pt 6):1983–1990PubMedCrossRefGoogle Scholar
  6. Azevedo FA, Carvalho LR, Grinberg LT, Farfel JM, Ferretti RE, Leite RE, Jacob Filho W, Lent R, Herculano-Houzel S (2009) Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J Comp Neurol 513:532–541PubMedCrossRefGoogle Scholar
  7. Bachis A, Cruz MI, Nosheny RL, Mocchetti I (2008) Chronic unpredictable stress promotes neuronal apoptosis in the cerebral cortex. Neurosci Lett 442:104–108PubMedCrossRefGoogle Scholar
  8. Banasr M, Valentine GW, Li XY, Gourley SL, Taylor JR, Duman RS (2007) Chronic unpredictable stress decreases cell proliferation in the cerebral cortex of the adult rat. Biol Psychiatry 62:496–504PubMedCrossRefGoogle Scholar
  9. Becker LE, Armstrong DL, Chan F, Wood MM (1984) Dendritic development in human occipital cortical neurons. Brain Res 315:117–124PubMedGoogle Scholar
  10. Bell MA, Ball MJ (1985) Laminar variation in the microvascular architecture of normal human visual cortex (area 17). Brain Res 335:139–143PubMedCrossRefGoogle Scholar
  11. Benes FM, Parks TN, Rubel EW (1977) Rapid dendritic atrophy following deafferentation: an EM morphometric analysis. Brain Res 122:1–13PubMedCrossRefGoogle Scholar
  12. Bennett MR (2011) The prefrontal-limbic network in depression: a core pathology of synapse regression. Prog Neurobiol 93:457–467PubMedCrossRefGoogle Scholar
  13. Bock J, Gruss M, Becker S, Braun K (2005) Experience-induced changes of dendritic spine densities in the prefrontal and sensory cortex: correlation with developmental time windows. Cereb Cortex 15:802–808PubMedCrossRefGoogle Scholar
  14. Bogoch Y, Biala YN, Linial M, Weinstock M (2007) Anxiety induced by prenatal stress is associated with suppression of hippocampal genes involved in synaptic function. J Neurochem 101:1018–1030PubMedCrossRefGoogle Scholar
  15. Bolmont T, Haiss F, Eicke D, Radde R, Mathis CA, Klunk WE, Kohsaka S, Jucker M, Calhoun ME (2008) Dynamics of the microglial/amyloid interaction indicate a role in plaque maintenance. J Neurosci 28:4283–4292PubMedCrossRefGoogle Scholar
  16. Bolstad I, Leergaard TB, Bjaalie JG (2007) Branching of individual somatosensory cerebropontine axons in rat: evidence of divergence. Brain Struct Funct 212:85–93PubMedCrossRefGoogle Scholar
  17. Borcel E, Perez-Alvarez L, Herrero AI, Brionne T, Varea E, Berezin V, Bock E, Sandi C, Venero C (2008) Chronic stress in adulthood followed by intermittent stress impairs spatial memory and the survival of newborn hippocampal cells in aging animals: prevention by FGL, a peptide mimetic of neural cell adhesion molecule. Behav Pharmacol 19:41–49PubMedCrossRefGoogle Scholar
  18. Braitenberg V, Schuz A (1998) Cortex: statistics and geometry of neuronal connectivity. Springer, BerlinCrossRefGoogle Scholar
  19. Braun K, Antemano R, Helmeke C, Buchner M, Poeggel G (2009) Juvenile separation stress induces rapid region- and layer-specific changes in S100ss- and glial fibrillary acidic protein-immunoreactivity in astrocytes of the rodent medial prefrontal cortex. Neuroscience 160:629–638PubMedCrossRefGoogle Scholar
  20. Broman J, Flink R, Westman J (1987) Postnatal development of the feline lateral cervical nucleus: I. A quantitative light and electron microscopic study. J Comp Neurol 260:539–551PubMedCrossRefGoogle Scholar
  21. Brown SM, Henning S, Wellman CL (2005) Mild, short-term stress alters dendritic morphology in rat medial prefrontal cortex. Cereb Cortex 15:1714–1722PubMedCrossRefGoogle Scholar
  22. Burke HM, Davis MC, Otte C, Mohr DC (2005) Depression and cortisol responses to psychological stress: a meta-analysis. Psychoneuroendocrinology 30:846–856PubMedCrossRefGoogle Scholar
  23. Bushong EA, Martone ME, Jones YZ, Ellisman MH (2002) Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains. J Neurosci 22:183–192PubMedGoogle Scholar
  24. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R (2003) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301:386–389PubMedCrossRefGoogle Scholar
  25. Cerqueira JJ, Catania C, Sotiropoulos I, Schubert M, Kalisch R, Almeida OF, Auer DP, Sousa N (2005) Corticosteroid status influences the volume of the rat cingulate cortex – a magnetic resonance imaging study. J Psychiatr Res 39:451–460PubMedCrossRefGoogle Scholar
  26. Chen H, Pandey GN, Dwivedi Y (2006) Hippocampal cell proliferation regulation by repeated stress and antidepressants. Neuroreport 17:863–867PubMedCrossRefGoogle Scholar
  27. Chvatal A, Anderova M, Ziak D, Orkand RK, Sykova E (2001) Membrane currents and morphological properties of neurons and glial cells in the spinal cord and filum terminale of the frog. Neurosci Res 40:23–35PubMedCrossRefGoogle Scholar
  28. Conrad CD, Ledoux JE, Magarinos AM, McEwen BS (1999) Repeated restraint stress facilitates fear conditioning independently of causing hippocampal CA3 dendritic atrophy. Behav Neurosci 113:902–913PubMedCrossRefGoogle Scholar
  29. Cook SC, Wellman CL (2004) Chronic stress alters dendritic morphology in rat medial prefrontal cortex. J Neurobiol 60:236–248PubMedCrossRefGoogle Scholar
  30. Cotter D, Mackay D, Landau S, Kerwin R, Everall I (2001a) Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry 58:545–553PubMedCrossRefGoogle Scholar
  31. Cotter DR, Pariante CM, Everall IP (2001b) Glial cell abnormalities in major psychiatric disorders: the evidence and implications. Brain Res Bull 55:585–595PubMedCrossRefGoogle Scholar
  32. Cotter D, Landau S, Beasley C, Stevenson R, Chana G, Macmillan L, Everall I (2002a) The density and spatial distribution of GABAergic neurons, labelled using calcium binding proteins, in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia. Biol Psychiatry 51:377–386PubMedCrossRefGoogle Scholar
  33. Cotter D, Mackay D, Chana G, Beasley C, Landau S, Everall IP (2002b) Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. Cereb Cortex 12:386–394PubMedCrossRefGoogle Scholar
  34. Cragg BG (1967) The density of synapses and neurones in the motor and visual areas of the cerebral cortex. J Anat 101:639–654PubMedGoogle Scholar
  35. Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M, Bartolomucci A, Fuchs E (2001) Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci U S A 98:12796–12801PubMedCrossRefGoogle Scholar
  36. Czeh B, Muller-Keuker JI, Rygula R, Abumaria N, Hiemke C, Domenici E, Fuchs E (2007) Chronic social stress inhibits cell proliferation in the adult medial prefrontal cortex: hemispheric asymmetry and reversal by fluoxetine treatment. Neuropsychopharmacology 32:1490–1503PubMedCrossRefGoogle Scholar
  37. Czeh B, Perez-Cruz C, Fuchs E, Flugge G (2008) Chronic stress-induced cellular changes in the medial prefrontal cortex and their potential clinical implications: does hemisphere location matter? Behav Brain Res 190:1–13PubMedCrossRefGoogle Scholar
  38. D’Ambrosio R, Wenzel J, Schwartzkroin PA, McKhann GM 2nd, Janigro D (1998) Functional specialization and topographic segregation of hippocampal astrocytes. J Neurosci 18:4425–4438PubMedGoogle Scholar
  39. Dalla C, Whetstone AS, Hodes GE, Shors TJ (2009) Stressful experience has opposite effects on dendritic spines in the hippocampus of cycling versus masculinized females. Neurosci Lett 449:52–56PubMedCrossRefGoogle Scholar
  40. Defelipe J, Marco P, Busturia I, Merchan-Perez A (1999) Estimation of the number of synapses in the cerebral cortex: methodological considerations. Cereb Cortex 9:722–732PubMedCrossRefGoogle Scholar
  41. Defelipe J, Alonso-Nanclares L, Arellano JI (2002) Microstructure of the neocortex: comparative aspects. J Neurocytol 31:299–316PubMedCrossRefGoogle Scholar
  42. Deitch JS, Rubel EW (1989a) Changes in neuronal cell bodies in N. laminaris during deafferentation-induced dendritic atrophy. J Comp Neurol 281:259–268PubMedCrossRefGoogle Scholar
  43. Deitch JS, Rubel EW (1989b) Rapid changes in ultrastructure during deafferentation-induced dendritic atrophy. J Comp Neurol 281:234–258PubMedCrossRefGoogle Scholar
  44. Dekosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol 27:457–464PubMedCrossRefGoogle Scholar
  45. Donohue HS, Gabbott PL, Davies HA, Rodriguez JJ, Cordero MI, Sandi C, Medvedev NI, Popov VI, Colyer FM, Peddie CJ, Stewart MG (2006) Chronic restraint stress induces changes in synapse morphology in stratum lacunosum-moleculare CA1 rat hippocampus: a stereological and three-dimensional ultrastructural study. Neuroscience 140:597–606PubMedCrossRefGoogle Scholar
  46. Drevets WC (2007) Orbitofrontal cortex function and structure in depression. Ann N Y Acad Sci 1121:499–527PubMedCrossRefGoogle Scholar
  47. Drevets WC, Savitz J, Trimble M (2008) The subgenual anterior cingulate cortex in mood disorders. CNS Spectr 13:663–681PubMedGoogle Scholar
  48. Dupret D, Fabre A, Dobrossy MD, Panatier A, Rodriguez JJ, Lamarque S, Lemaire V, Oliet SH, Piazza PV, Abrous DN (2007) Spatial learning depends on both the addition and removal of new hippocampal neurons. PLoS Biol 5:e214PubMedCrossRefGoogle Scholar
  49. Dwork AJ, Christensen JR, Larsen KB, Scalia J, Underwood MD, Arango V, Pakkenberg B, Lisanby SH (2009) Unaltered neuronal and glial counts in animal models of magnetic seizure therapy and electroconvulsive therapy. Neuroscience 164:1557–1564PubMedCrossRefGoogle Scholar
  50. Eastwood SL, Harrison PJ (2000) Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs. Mol Psychiatry 5:425–432PubMedCrossRefGoogle Scholar
  51. Eastwood SL, Harrison PJ (2001) Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a Western blot study of synaptophysin, GAP-43 and the complexins. Brain Res Bull 55:569–578PubMedCrossRefGoogle Scholar
  52. Englisch HJ, Kunz G, Wenzel J (1974) Distribution of spines on the pyramidal neurons in the CA-1 region of the hippocampus in the rat. Z Mikrosk Anat Forsch 88:85–102PubMedGoogle Scholar
  53. Fabricius K, Pakkenberg H, Pakkenberg B (2007) No changes in neocortical cell volumes or glial cell numbers in chronic alcoholic subjects compared to control subjects. Alcohol Alcohol 42:400–406PubMedGoogle Scholar
  54. Foh E, Haug H, Konig M, Rast A (1973) Determination of quantitative parameters of the fine structure in the visual cortex of the cat, also a methodological contribution on measuring the neuropil (author’s transl). Microsc Acta 75:148–168PubMedGoogle Scholar
  55. Frotscher M, Nitsch C, Hassler R (1981) Synaptic reorganization in the rabbit hippocampus after lesion of commissural afferents. Anat Embryol (Berl) 163:15–30CrossRefGoogle Scholar
  56. Fujimoto T, Takeuch K, Matsumoto T, Kamimura K, Hamada R, Nakamura K, Kato N (2007) Abnormal glucose metabolism in the anterior cingulate cortex in patients with schizophrenia. Psychiatry Res 154:49–58PubMedCrossRefGoogle Scholar
  57. Fujioka A, Fujioka T, Ishida Y, Maekawa T, Nakamura S (2006) Differential effects of prenatal stress on the morphological maturation of hippocampal neurons. Neuroscience 141:907–915PubMedCrossRefGoogle Scholar
  58. Garrett JE, Wellman CL (2009) Chronic stress effects on dendritic morphology in medial prefrontal cortex: sex differences and estrogen dependence. Neuroscience 162:195–207PubMedCrossRefGoogle Scholar
  59. Goldwater DS, Pavlides C, Hunter RG, Bloss EB, Hof PR, McEwen BS, Morrison JH (2009) Structural and functional alterations to rat medial prefrontal cortex following chronic restraint stress and recovery. Neuroscience 164:798–808PubMedCrossRefGoogle Scholar
  60. Gos T, Bock J, Poeggel G, Braun K (2008) Stress-induced synaptic changes in the rat anterior cingulate cortex are dependent on endocrine developmental time windows. Synapse 62:229–232PubMedCrossRefGoogle Scholar
  61. Griph S, Westman J (1977) Volume composition of the lateral cervical nucleus in the cat. I. A stereological and electron microscopical study of normal and deafferentated animals. J Neurocytol 6:723–743PubMedCrossRefGoogle Scholar
  62. Hajszan T, Dow A, Warner-Schmidt JL, Szigeti-Buck K, Sallam NL, Parducz A, Leranth C, Duman RS (2009) Remodeling of hippocampal spine synapses in the rat learned helplessness model of depression. Biol Psychiatry 65:392–400PubMedCrossRefGoogle Scholar
  63. Hama K, Arii T, Katayama E, Marton M, Ellisman MH (2004) Tri-dimensional morphometric analysis of astrocytic processes with high voltage electron microscopy of thick Golgi preparations. J Neurocytol 33:277–285PubMedCrossRefGoogle Scholar
  64. Hammen C (2005) Stress and depression. Annu Rev Clin Psychol 1:293–319PubMedCrossRefGoogle Scholar
  65. Hamori J (1990) Morphological plasticity of postsynaptic neurones in reactive synaptogenesis. J Exp Biol 153:251–260PubMedGoogle Scholar
  66. Hayashi A, Nagaoka M, Yamada K, Ichitani Y, Miake Y, Okado N (1998) Maternal stress induces synaptic loss and developmental disabilities of offspring. Int J Dev Neurosci 16:209–216PubMedCrossRefGoogle Scholar
  67. Helmeke C, Seidel K, Poeggel G, Bredy TW, Abraham A, Braun K (2009) Paternal deprivation during infancy results in dendrite- and time-specific changes of dendritic development and spine formation in the orbitofrontal cortex of the biparental rodent Octodon degus. Neuroscience 163:790–798PubMedCrossRefGoogle Scholar
  68. Hoff SF (1986) Lesion-induced transneuronal plasticity in the adult rat hippocampus. Neuroscience 19:1227–1233PubMedCrossRefGoogle Scholar
  69. Honer WG, Falkai P, Chen C, Arango V, Mann JJ, Dwork AJ (1999) Synaptic and plasticity-associated proteins in anterior frontal cortex in severe mental illness. Neuroscience 91:1247–1255PubMedCrossRefGoogle Scholar
  70. Hosseini-Sharifabad M, Nyengaard JR (2007) Design-based estimation of neuronal number and individual neuronal volume in the rat hippocampus. J Neurosci Methods 162:206–214PubMedCrossRefGoogle Scholar
  71. Huot RL, Plotsky PM, Lenox RH, McNamara RK (2002) Neonatal maternal separation reduces hippocampal mossy fiber density in adult Long Evans rats. Brain Res 950:52–63PubMedCrossRefGoogle Scholar
  72. Huttenlocher PR (1990) Morphometric study of human cerebral cortex development. Neuropsy­chologia 28:517–527PubMedCrossRefGoogle Scholar
  73. Jacobs B, Scheibel AB (1993) A quantitative dendritic analysis of Wernicke’s area in humans. I. Lifespan changes. J Comp Neurol 327:83–96PubMedCrossRefGoogle Scholar
  74. Jacobs B, Batal HA, Lynch B, Ojemann G, Ojemann LM, Scheibel AB (1993a) Quantitative dendritic and spine analyses of speech cortices: a case study. Brain Lang 44:239–253PubMedCrossRefGoogle Scholar
  75. Jacobs B, Schall M, Scheibel AB (1993b) A quantitative dendritic analysis of Wernicke’s area in humans. II. Gender, hemispheric, and environmental factors. J Comp Neurol 327:97–111PubMedCrossRefGoogle Scholar
  76. Jacobs B, Schall M, Prather M, Kapler E, Driscoll L, Baca S, Jacobs J, Ford K, Wainwright M, Treml M (2001) Regional dendritic and spine variation in human cerebral cortex: a quantitative golgi study. Cereb Cortex 11:558–571PubMedCrossRefGoogle Scholar
  77. James GA, Kelley ME, Craddock RC, Holtzheimer PE, Dunlop BW, Nemeroff CB, Mayberg HS, Hu XP (2009) Exploratory structural equation modeling of resting-state fMRI: applicability of group models to individual subjects. Neuroimage 45:778–787PubMedCrossRefGoogle Scholar
  78. Jayatissa MN, Bisgaard CF, West MJ, Wiborg O (2008) The number of granule cells in rat hippocampus is reduced after chronic mild stress and re-established after chronic escitalopram treatment. Neuropharmacology 54:530–541PubMedCrossRefGoogle Scholar
  79. Johnston-Wilson NL, Sims CD, Hofmann JP, Anderson L, Shore AD, Torrey EF, Yolken RH (2000) Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium. Mol Psychiatry 5:142–149PubMedCrossRefGoogle Scholar
  80. Kassem MS, Lagopoulos J, Stait-Gardner T, Price WS, Chohan TW, Arnold JC, Hatton SN, Bennett MR (2012) Stress-induced grey matter loss determined by MRI is primarily due to loss of dendrites and their synapses. Mol Neurobiol; NovGoogle Scholar
  81. Kendler KS, Karkowski LM, Prescott CA (1999) Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 156:837–841PubMedGoogle Scholar
  82. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE (2005) Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 62:617–627PubMedCrossRefGoogle Scholar
  83. Kessler RC, Davis CG, Kendler KS (1997) Childhood adversity and adult psychiatric disorder in the US National Comorbidity Survey. Psychol Med 27:1101–1119PubMedCrossRefGoogle Scholar
  84. Koolschijn PC, van Haren NE, Lensvelt-Mulders GJ, Hulshoff Pol HE, Kahn RS (2009) Brain volume abnormalities in major depressive disorder: a meta-analysis of magnetic resonance imaging studies. Hum Brain Mapp 30:3719–3735PubMedCrossRefGoogle Scholar
  85. Lambert KG, Gerecke KM, Quadros PS, Doudera E, Jasnow AM, Kinsley CH (2000) Activity-stress increases density of GFAP-immunoreactive astrocytes in the rat hippocampus. Stress 3:275–284PubMedCrossRefGoogle Scholar
  86. Lehmenkuhler A, Sykova E, Svoboda J, Zilles K, Nicholson C (1993) Extracellular space parameters in the rat neocortex and subcortical white matter during postnatal development determined by diffusion analysis. Neuroscience 55:339–351PubMedCrossRefGoogle Scholar
  87. Lennie P (2003) The cost of cortical computation. Curr Biol 13:493–497PubMedCrossRefGoogle Scholar
  88. Leventopoulos M, Ruedi-Bettschen D, Knuesel I, Feldon J, Pryce CR, Opacka-Juffry J (2007) Long-term effects of early life deprivation on brain glia in Fischer rats. Brain Res 1142:119–126PubMedCrossRefGoogle Scholar
  89. Liston C, Miller MM, Goldwater DS, Radley JJ, Rocher AB, Hof PR, Morrison JH, McEwen BS (2006) Stress-induced alterations in prefrontal cortical dendritic morphology predict selective impairments in perceptual attentional set-shifting. J Neurosci 26:7870–7874PubMedCrossRefGoogle Scholar
  90. Liu RJ, Aghajanian GK (2008) Stress blunts serotonin- and hypocretin-evoked EPSCs in prefrontal cortex: role of corticosterone-mediated apical dendritic atrophy. Proc Natl Acad Sci U S A 105:359–364PubMedCrossRefGoogle Scholar
  91. Llorente R, Llorente-Berzal A, Petrosino S, Marco EM, Guaza C, Prada C, Lopez-Gallardo M, di Marzo V, Viveros MP (2008) Gender-dependent cellular and biochemical effects of maternal deprivation on the hippocampus of neonatal rats: a possible role for the endocannabinoid system. Dev Neurobiol 68:1334–1347PubMedCrossRefGoogle Scholar
  92. Lloyd SA, Wensley B, Faherty CJ, Smeyne RJ (2003) Regional differences in cortical dendrite morphology following in utero exposure to cocaine. Brain Res Dev Brain Res 147:59–66PubMedCrossRefGoogle Scholar
  93. Martinez-Tellez RI, Hernandez-Torres E, Gamboa C, Flores G (2009) Prenatal stress alters spine density and dendritic length of nucleus accumbens and hippocampus neurons in rat offspring. Synapse 63:794–804PubMedCrossRefGoogle Scholar
  94. Matthews DA, Cotman C, Lynch G (1976a) An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. I. Magnitude and time course of degeneration. Brain Res 115:1–21PubMedCrossRefGoogle Scholar
  95. Matthews DA, Cotman C, Lynch G (1976b) An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. II. Reappearance of morphologically normal synaptic contacts. Brain Res 115:23–41PubMedCrossRefGoogle Scholar
  96. Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA, Silva JA, Tekell JL, Martin CC, Lancaster JL, Fox PT (1999) Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry 156:675–682PubMedGoogle Scholar
  97. McEwen BS (2000) The neurobiology of stress: from serendipity to clinical relevance. Brain Res 886:172–189PubMedCrossRefGoogle Scholar
  98. McLaughlin KJ, Gomez JL, Baran SE, Conrad CD (2007) The effects of chronic stress on hippocampal morphology and function: an evaluation of chronic restraint paradigms. Brain Res 1161:56–64PubMedCrossRefGoogle Scholar
  99. Michelsen KA, van den Hove DL, Schmitz C, Segers O, Prickaerts J, Steinbusch HW (2007) Prenatal stress and subsequent exposure to chronic mild stress influence dendritic spine density and morphology in the rat medial prefrontal cortex. BMC Neurosci 8:107PubMedCrossRefGoogle Scholar
  100. Miguel-Hidalgo JJ, Baucom C, Dilley G, Overholser JC, Meltzer HY, Stockmeier CA, Rajkowska G (2000) Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder. Biol Psychiatry 48:861–873PubMedCrossRefGoogle Scholar
  101. Minkwitz HG, Holz L (1975) The ontogenetic development of pyramidal neurons in the hippocampus (CA1) of the rat. J Hirnforsch 16:37–54PubMedGoogle Scholar
  102. Mizoguchi K, Kunishita T, Chui DH, Tabira T (1992) Stress induces neuronal death in the hippocampus of castrated rats. Neurosci Lett 138:157–160PubMedCrossRefGoogle Scholar
  103. Murmu MS, Salomon S, Biala Y, Weinstock M, Braun K, Bock J (2006) Changes of spine density and dendritic complexity in the prefrontal cortex in offspring of mothers exposed to stress during pregnancy. Eur J Neurosci 24:1477–1487PubMedCrossRefGoogle Scholar
  104. Musholt K, Cirillo G, Cavaliere C, Rosaria Bianco M, Bock J, Helmeke C, Braun K Papa M (2009) Neonatal separation stress reduces glial fibrillary acidic protein- and S100beta-immunoreactive astrocytes in the rat medial precentral cortex. Dev Neurobiol 69:203–211PubMedCrossRefGoogle Scholar
  105. Namestkova K, Simonova Z, Sykova E (2005) Decreased proliferation in the adult rat hippocampus after exposure to the Morris water maze and its reversal by fluoxetine. Behav Brain Res 163:26–32PubMedCrossRefGoogle Scholar
  106. Nawroth JC, Greer CA, Chen WR, Laughlin SB, Shepherd GM (2007) An energy budget for the olfactory glomerulus. J Neurosci 27:9790–9800PubMedCrossRefGoogle Scholar
  107. Nicholson C, Phillips JM (1981) Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum. J Physiol 321:225–257PubMedGoogle Scholar
  108. Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 308:1314–1318PubMedCrossRefGoogle Scholar
  109. Oberheim NA, Takano T, Han X, He W, Lin JH, Wang F, Xu Q, Wyatt JD, Pilcher W, Ojemann JG, Ransom BR, Goldman SA, Nedergaard M (2009) Uniquely hominid features of adult human astrocytes. J Neurosci 29:3276–3287PubMedCrossRefGoogle Scholar
  110. Ongur D, Drevets WC, Price JL (1998) Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci U S A 95:13290–13295PubMedCrossRefGoogle Scholar
  111. Oomen CA, Girardi CE, Cahyadi R, Verbeek EC, Krugers H, Joels M, Lucassen PJ (2009) Opposite effects of early maternal deprivation on neurogenesis in male versus female rats. PLoS One 4:e3675PubMedCrossRefGoogle Scholar
  112. Pakkenberg B, Gundersen HJ (1997) Neocortical neuron number in humans: effect of sex and age. J Comp Neurol 384:312–320PubMedCrossRefGoogle Scholar
  113. Paula-Barbosa MM, Saraiva A, Tavares MA, Borges MM, Verwer RW (1986) Alzheimer’s disease: maintenance of neuronal and synaptic densities in frontal cortical layers II and III. Acta Neurol Scand 74:404–408PubMedCrossRefGoogle Scholar
  114. Pelvig DP, Pakkenberg H, Stark AK, Pakkenberg B (2008) Neocortical glial cell numbers in human brains. Neurobiol Aging 29:1754–1762PubMedCrossRefGoogle Scholar
  115. Pennington K, Dicker P, Hudson L, Cotter DR (2008) Evidence for reduced neuronal somal size within the insular cortex in schizophrenia, but not in affective disorders. Schizophr Res 106:164–171PubMedCrossRefGoogle Scholar
  116. Perez-Cruz C, Muller-Keuker JI, Heilbronner U, Fuchs E, Flugge G (2007) Morphology of pyramidal neurons in the rat prefrontal cortex: lateralized dendritic remodeling by chronic stress. Neural Plast 2007:46276PubMedCrossRefGoogle Scholar
  117. Pilgrim C, Reisert I, Grab D (1982) Volume densities and specific surfaces of neuronal and glial tissue elements in the rat supraoptic nucleus. J Comp Neurol 211:427–431PubMedCrossRefGoogle Scholar
  118. Pokorny J, Yamamoto T (1981a) Postnatal ontogenesis of hippocampal CA1 area in rats. I. Development of dendritic arborisation in pyramidal neurons. Brain Res Bull 7:113–120PubMedCrossRefGoogle Scholar
  119. Pokorny J, Yamamoto T (1981b) Postnatal ontogenesis of hippocampal CA1 area in rats. II. Development of ultrastructure in stratum lacunosum and moleculare. Brain Res Bull 7:121–130PubMedCrossRefGoogle Scholar
  120. Rabinowicz T, Petetot JM, Gartside PS, Sheyn D, Sheyn T, De CM (2002) Structure of the cerebral cortex in men and women. J Neuropathol Exp Neurol 61:46–57PubMedGoogle Scholar
  121. Radley JJ, Sisti HM, Hao J, Rocher AB, McCall T, Hof PR, McEwen BS, Morrison JH (2004) Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience 125:1–6PubMedCrossRefGoogle Scholar
  122. Radley JJ, Rocher AB, Janssen WGM, Hof PR, McEwen BS, Morrison JH (2005) Reversibility of apical dendritic retraction in the rat medial prefrontal cortex following repeated stress. Exp Neurol 196:199–203PubMedCrossRefGoogle Scholar
  123. Radley JJ, Rocher AB, Miller M, Janssen WGM, Liston C, Hof PR, McEwen BS, Morrison JH (2006) Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex. Cereb Cortex 16:313–320PubMedCrossRefGoogle Scholar
  124. Radley JJ, Rocher AB, Rodriguez A, Ehlenberger DB, Dammann M, McEwen BS, Morrison JH, Wearne SL, Hof PR (2008) Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex. J Comp Neurol 507:1141–1150PubMedCrossRefGoogle Scholar
  125. Rajasekharan S, Baker KA, Horn KE, Jarjour AA, Antel JP, Kennedy TE (2009) Netrin 1 and Dcc regulate oligodendrocyte process branching and membrane extension via Fyn and RhoA. Development 136:415–426PubMedCrossRefGoogle Scholar
  126. Rajkowska G (2000) Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry 48:766–777PubMedCrossRefGoogle Scholar
  127. Rajkowska G, Selemon LD, Goldman-Rakic PS (1998) Neuronal and glial somal size in the prefrontal cortex: a postmortem morphometric study of schizophrenia and Huntington disease. Arch Gen Psychiatry 55:215–224PubMedCrossRefGoogle Scholar
  128. Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY, Overholser JC, Roth BL, Stockmeier CA (1999) Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 45:1085–1098PubMedCrossRefGoogle Scholar
  129. Richter-Landsberg C (2008) The cytoskeleton in oligodendrocytes. Microtubule dynamics in health and disease. J Mol Neurosci 35:55–63PubMedCrossRefGoogle Scholar
  130. Rockland KS, Virga A (1990) Organization of individual cortical axons projecting from area V1 (area 17) to V2 (area 18) in the macaque monkey. Vis Neurosci 4:11–28PubMedCrossRefGoogle Scholar
  131. Rosenbrock H, Koros E, Bloching A, Podhorna J, Borsini F (2005) Effect of chronic intermittent restraint stress on hippocampal expression of marker proteins for synaptic plasticity and progenitor cell proliferation in rats. Brain Res 1040:55–63PubMedCrossRefGoogle Scholar
  132. Russell FA, Moore DR (1999) Effects of unilateral cochlear removal on dendrites in the gerbil medial superior olivary nucleus. Eur J Neurosci 11:1379–1390PubMedCrossRefGoogle Scholar
  133. Sabbatini M, Strocchi P, Vitaioli L, Amenta F (2000) The hippocampus in spontaneously hypertensive rats: a quantitative microanatomical study. Neuroscience 100:251–258PubMedCrossRefGoogle Scholar
  134. Sandi C, Davies HA, Cordero MI, Rodriguez JJ, Popov VI, Stewart MG (2003) Rapid reversal of stress induced loss of synapses in CA3 of rat hippocampus following water maze training. Eur J Neurosci 17:2447–2456PubMedCrossRefGoogle Scholar
  135. Savitz JB, Drevets WC (2009) Imaging phenotypes of major depressive disorder: genetic correlates. Neuroscience 164:300–330PubMedCrossRefGoogle Scholar
  136. Scheff SW, Price DA (2001) Alzheimer’s disease-related synapse loss in the cingulate cortex. J Alzheimers Dis 3:495–505PubMedGoogle Scholar
  137. Scheff SW, Price DA (2003) Synaptic pathology in Alzheimer’s disease: a review of ultrastructural studies. Neurobiol Aging 24:1029–1046PubMedCrossRefGoogle Scholar
  138. Scheff SW, Price DA (2006) Alzheimer’s disease-related alterations in synaptic density: neocortex and hippocampus. J Alzheimers Dis 9:101–115PubMedGoogle Scholar
  139. Scheff SW, Dekosky ST, Price DA (1990) Quantitative assessment of cortical synaptic density in Alzheimer’s disease. Neurobiol Aging 11:29–37PubMedCrossRefGoogle Scholar
  140. Shansky RM, Morrison JH (2009) Stress-induced dendritic remodeling in the medial prefrontal cortex: effects of circuit, hormones and rest. Brain Res 1293:108–113PubMedCrossRefGoogle Scholar
  141. Sholl DA (1953) Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat 87:387–406PubMedGoogle Scholar
  142. Silva-Gomez AB, Rojas D, Juarez I, Flores G (2003) Decreased dendritic spine density on prefrontal cortical and hippocampal pyramidal neurons in postweaning social isolation rats. Brain Res 983:128–136PubMedCrossRefGoogle Scholar
  143. Somogyi J, Eysel U, Hamori J (1987) A quantitative study of morphological reorganization following chronic optic deafferentation in the adult cat dorsal lateral geniculate nucleus. J Comp Neurol 255:341–350PubMedCrossRefGoogle Scholar
  144. Song J, Goetz BD, Baas PW, Duncan ID (2001) Cytoskeletal reorganization during the formation of oligodendrocyte processes and branches. Mol Cell Neurosci 17:624–636PubMedCrossRefGoogle Scholar
  145. Sorensen SA, Rubel EW (2006) The level and integrity of synaptic input regulates dendrite structure. J Neurosci 26:1539–1550PubMedCrossRefGoogle Scholar
  146. Spacek J, Hartmann M (1983) Three-dimensional analysis of dendritic spines. I. Quantitative observations related to dendritic spine and synaptic morphology in cerebral and cerebellar cortices. Anat Embryol (Berl) 167:289–310CrossRefGoogle Scholar
  147. Stepanyants A, Tamas G, Chklovskii DB (2004) Class-specific features of neuronal wiring. Neuron 43:251–259PubMedCrossRefGoogle Scholar
  148. Stepanyants A, Martinez LM, Ferecsko AS, Kisvarday ZF (2009) The fractions of short- and long-range connections in the visual cortex. Proc Natl Acad Sci U S A 106:3555–3560PubMedCrossRefGoogle Scholar
  149. Stewart MG, Davies HA, Sandi C, Kraev IV, Rogachevsky VV, Peddie CJ, Rodriguez JJ, Cordero MI, Donohue HS, Gabbott PL, Popov VI (2005) Stress suppresses and learning induces plasticity in CA3 of rat hippocampus: a three-dimensional ultrastructural study of thorny excrescences and their postsynaptic densities. Neuroscience 131:43–54PubMedCrossRefGoogle Scholar
  150. Swaab DF, Bao AM, Lucassen PJ (2005) The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 4:141–194PubMedCrossRefGoogle Scholar
  151. Sykova E, Vorisek I, Antonova T, Mazel T, Meyer-Luehmann M, Jucker M, Hajek M, Ort M, Bures J (2005a) Changes in extracellular space size and geometry in APP23 transgenic mice: a model of Alzheimer’s disease. Proc Natl Acad Sci U S A 102:479–484PubMedCrossRefGoogle Scholar
  152. Sykova E, Vorisek I, Mazel T, Antonova T, Schachner M (2005b) Reduced extracellular space in the brain of tenascin-R- and HNK-1-sulphotransferase deficient mice. Eur J Neurosci 22:1873–1880PubMedCrossRefGoogle Scholar
  153. Tan H-Y, Callicott JH, Weinberger DR (2007) Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis and schizophrenia. Cereb Cortex 17:i171–i181PubMedCrossRefGoogle Scholar
  154. Taylor SF, Liberzon I (2007) Neural correlates of emotion regulation in psychopathology. Trends Cogn Sci 11:413–418PubMedCrossRefGoogle Scholar
  155. Thomas RM, Hotsenpiller G, Peterson DA (2007) Acute psychosocial stress reduces cell survival in adult hippocampal neurogenesis without altering proliferation. J Neurosci 27:2734–2743PubMedCrossRefGoogle Scholar
  156. Toft MH, Gredal O, Pakkenberg B (2005) The size distribution of neurons in the motor cortex in amyotrophic lateral sclerosis. J Anat 207:399–407PubMedCrossRefGoogle Scholar
  157. Trommald M, Jensen V, Andersen P (1995) Analysis of dendritic spines in rat CA1 pyramidal cells intracellularly filled with a fluorescent dye. J Comp Neurol 353:260–274PubMedCrossRefGoogle Scholar
  158. Veena J, Srikumar BN, Mahati K, Bhagya V, Raju TR, Shankaranarayana Rao BS (2009a) Enriched environment restores hippocampal cell proliferation and ameliorates cognitive deficits in chronically stressed rats. J Neurosci Res 87:831–843PubMedCrossRefGoogle Scholar
  159. Veena J, Srikumar BN, Raju TR, Shankaranarayana Rao BS (2009b) Exposure to enriched environment restores the survival and differentiation of new born cells in the hippocampus and ameliorates depressive symptoms in chronically stressed rats. Neurosci Lett 455:178–182PubMedCrossRefGoogle Scholar
  160. Vostrikov VM (2007) Decreased numerical density of pericapillary oligodendrocytes in the cortex in schizophrenia. Zh Nevrol Psikhiatr Im S S Korsakova 107:58–65PubMedGoogle Scholar
  161. Vostrikov VM, Uranova NA, Orlovskaya DD (2007) Deficit of perineuronal oligodendrocytes in the prefrontal cortex in schizophrenia and mood disorders. Schizophr Res 94:273–280PubMedCrossRefGoogle Scholar
  162. Vostrikov V, Orlovskaya D, Uranova N (2008) Deficit of pericapillary oligodendrocytes in the prefrontal cortex in schizophrenia. World J Biol Psychiatry 9:34–42PubMedCrossRefGoogle Scholar
  163. Watanabe Y, Gould E, McEwen BS (1992) Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 588:341–345PubMedCrossRefGoogle Scholar
  164. Westenbroek C, den Boer JA, Veenhuis M, ter Horst GJ (2004) Chronic stress and social housing differentially affect neurogenesis in male and female rats. Brain Res Bull 64:303–308PubMedCrossRefGoogle Scholar
  165. Wilhelmsson U, Bushong EA, Price DL, Smarr BL, Phung V, Terada M, Ellisman MH, Pekny M (2006) Redefining the concept of reactive astrocytes as cells that remain within their unique domains upon reaction to injury. Proc Natl Acad Sci U S A 103:17513–17518PubMedCrossRefGoogle Scholar
  166. Wood GE, Young LT, Reagan LP, Chen B, McEwen BS (2004) Stress-induced structural remodeling in hippocampus: prevention by lithium treatment. Proc Natl Acad Sci U S A 101:3973–3978PubMedCrossRefGoogle Scholar
  167. Yao X, Hrabetova S, Nicholson C, Manley GT (2008) Aquaporin-4-deficient mice have increased extracellular space without tortuosity change. J Neurosci 28:5460–5464PubMedCrossRefGoogle Scholar
  168. Zhao H, Xu H, Xu X, Young D (2007) Predatory stress induces hippocampal cell death by apoptosis in rats. Neurosci Lett 421:115–120PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Maxwell Bennett
    • 1
  1. 1.Brain and Mind Research InstituteCamperdownAustralia

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