Skip to main content

Advertisement

SpringerLink
Log in

Expansion of mossy fibers and CA3 apical dendritic length accompanies the fall in dendritic spine density after gonadectomy in male, but not female, rats

  • Original Article
  • Published:
Brain Structure and Function Aims and scope Submit manuscript

Abstract

Androgen loss is an important clinical concern because of its cognitive and behavioral effects. Changes in androgen levels are also suspected to contribute to neurological disease. However, the available data on the effects of androgen deprivation in areas of the brain that are central to cognition, like the hippocampus, are mixed. In this study, morphological analysis of pyramidal cells was used to investigate if structural changes could potentially contribute to the mixed cognitive effects that have been observed after androgen loss in males. Male Sprague–Dawley rats were orchidectomized or sham-operated. Two months later, their brains were Golgi-impregnated for morphological analysis. Morphological endpoints were studied in areas CA3 and CA1, with comparisons to females either intact or 2 months after ovariectomy. CA3 pyramidal neurons of orchidectomized rats exhibited marked increases in apical dendritic arborization. There were increases in mossy fiber afferent density in area CA3, as well as robust enhancements to dendritic structure in area CA3 of orchidectomized males, but not in CA1. Remarkably, apical dendritic length of CA3 pyramidal cells increased, while spine density declined. By contrast, in females overall dendritic structure was minimally affected by ovariectomy, while dendritic spine density was greatly reduced. Sex differences and subfield-specific effects of gonadal hormone deprivation on the hippocampal circuitry may help explain the different behavioral effects reported in males and females after gonadectomy, or other conditions associated with declining gonadal hormone secretion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Abel KM, Drake R, Goldstein JM (2010) Sex differences in schizophrenia. Int Rev Psychiatry 22:417–428

    Article  PubMed  Google Scholar 

  • Alibhai SM, Breunis H, Timilshina N, Marzouk S, Stewart D, Tannock I, Naglie G, Tomlinson G, Fleshner N, Krahn M, Warde P, Canning SD (2010) Impact of androgen-deprivation therapy on cognitive function in men with nonmetastatic prostate cancer. J Clin Oncol 28:5030–5037

    Article  CAS  PubMed  Google Scholar 

  • Amanatkar HR, Chibnall JT, Seo BW, Manepalli JN, Grossberg GT (2014) Impact of exogenous testosterone on mood: a systematic review and meta-analysis of randomized placebo-controlled trials. Ann Clin Psychiatry 26:19–32

    PubMed  Google Scholar 

  • Atwi S, McMahon D, Scharfman HE, MacLusky NJ (2015) Androgen modulation of hippocampal structure and function. Neuroscientist 22(1):46–60

    Article  Google Scholar 

  • Aubele T, Kritzer MF (2012) Androgen influence on prefrontal dopamine systems in adult male rats: localization of cognate intracellular receptors in medial prefrontal projections to the ventral tegmental area and effects of gonadectomy and hormone replacement on glutamate-stimulated extracellular dopamine level. Cereb Cortex 22:1799–1812

    Article  CAS  PubMed  Google Scholar 

  • Bachevalier J, Hagger C (1991) Sex differences in the development of learning abilities in primates. Psychoneuroendocrinology 16:177–188

    Article  CAS  PubMed  Google Scholar 

  • Bennett MR, Lagopoulos J (2014) Stress and trauma: BDNF control of dendritic-spine formation and regression. Prog Neurobiol 112:80–99

    Article  CAS  PubMed  Google Scholar 

  • Cheng C, Trzcinski O, Doering LC (2014) Fluorescent labeling of dendritic spines in cell cultures with the carbocyanine dye “DiI”. Front Neuroanat 8:30

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheung ZH, Chin WH, Chen Y, Ng YP, Ip NY (2007) Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons. PLoS Biol 5:e63

    Article  PubMed  PubMed Central  Google Scholar 

  • Clancy AN, Bonsall RW, Michael RP (1992) Immunohistochemical labeling of androgen receptors in the brain of rat and monkey. Life Sci 50:409–417

    Article  CAS  PubMed  Google Scholar 

  • Conrad CD, McLaughlin KJ, Huynh TN, El-Ashmawy M, Sparks M (2012) Chronic stress and a cyclic regimen of estradiol administration separately facilitate spatial memory: relationship with hippocampal CA1 spine density and dendritic complexity. Behav Neurosci 126:142–156

    Article  CAS  PubMed  Google Scholar 

  • Das G, Reuhl K, Zhou R (2013) The Golgi–Cox method. Methods Mol Biol 1018:313–321

    Article  CAS  PubMed  Google Scholar 

  • DonCarlos LL, Garcia-Ovejero D, Sarkey S, Garcia-Segura LM, Azcoitia I (2003) Androgen receptor immunoreactivity in forebrain axons and dendrites in the rat. Endocrinology 144:3632–3638

    Article  CAS  PubMed  Google Scholar 

  • Edinger KL, Frye CA (2007) Androgens’ performance-enhancing effects in the inhibitory avoidance and water maze tasks may involve actions at intracellular androgen receptors in the dorsal hippocampus. Neurobiol Learn Mem 87:201–208

    Article  CAS  PubMed  Google Scholar 

  • Edwards HE, Burnham WM, MacLusky NJ (1999a) Testosterone and its metabolites affect afterdischarge thresholds and the development of amygdala kindled seizures. Brain Res 838:151–157

    Article  CAS  PubMed  Google Scholar 

  • Edwards HE, Burnham WM, Mendonca A, Bowlby DA, MacLusky NJ (1999b) Steroid hormones affect limbic afterdischarge thresholds and kindling rates in adult female rats. Brain Res 838:136–150

    Article  CAS  PubMed  Google Scholar 

  • Faulkner RL, Jang MH, Liu XB, Duan X, Sailor KA, Kim JY, Ge S, Jones EG, Ming GL, Song H, Cheng HJ (2008) Development of hippocampal mossy fiber synaptic outputs by new neurons in the adult brain. Proc Natl Acad Sci USA 105:14157–14162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frankfurt M, Luine V (2015) The evolving role of dendritic spines and memory: interaction(s) with estradiol. Horm Behav 74:28–36

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gazzaley AH, Weiland NG, McEwen BS, Morrison JH (1996) Differential regulation of NMDAR1 mRNA and protein by estradiol in the rat hippocampus. J Neurosci 16:6830–6838

    CAS  PubMed  Google Scholar 

  • Gibbs RB (1999) Treatment with estrogen and progesterone affects relative levels of brain-derived neurotrophic factor mRNA and protein in different regions of the adult rat brain. Brain Res 844:20–27

    Article  CAS  PubMed  Google Scholar 

  • Gonzales RB, DeLeon Galvan CJ, Rangel YM, Claiborne BJ (2001) Distribution of thorny excrescences on CA3 pyramidal neurons in the rat hippocampus. J Comp Neurol 430:357–368

    Article  CAS  PubMed  Google Scholar 

  • Gould E, Woolley CS, Frankfurt M, McEwen BS (1990) Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood. J Neurosci 10:1286–1291

    CAS  PubMed  Google Scholar 

  • Hajszan T, MacLusky NJ (2006) Neurologic links between epilepsy and depression in women: is hippocampal neuroplasticity the key? Neurology 66:S13–22

    Article  PubMed  Google Scholar 

  • Hajszan T, MacLusky NJ, Leranth C (2005) Short-term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus. Eur J Neurosci 21:1299–1303

    Article  PubMed  Google Scholar 

  • Hajszan T, Szigeti-Buck K, Sallam NL, Bober J, Parducz A, Maclusky NJ, Leranth C, Duman RS (2010) Effects of estradiol on learned helplessness and associated remodeling of hippocampal spine synapses in female rats. Biol Psychiatry 67:168–174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halpern DF, Benbow CP, Geary DC, Gur RC, Hyde JS, Gernsbacher MA (2007) The science of sex differences in science and mathematics. Psychol Sci Public Interest 8:1–51

    PubMed  PubMed Central  Google Scholar 

  • Hamilton AM, Oh WC, Vega-Ramirez H, Stein IS, Hell JW, Patrick GN, Zito K (2012) Activity-dependent growth of new dendritic spines is regulated by the proteasome. Neuron 74:1023–1030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamson DK, Wainwright SR, Taylor JR, Jones BA, Watson NV, Galea LA (2013) Androgens increase survival of adult-born neurons in the dentate gyrus by an androgen receptor-dependent mechanism in male rats. Endocrinology 154:3294–3304

    Article  CAS  PubMed  Google Scholar 

  • Hao J, Janssen WG, Tang Y, Roberts JA, McKay H, Lasley B, Allen PB, Greengard P, Rapp PR, Kordower JH, Hof PR, Morrison JH (2003) Estrogen increases the number of spinophilin-immunoreactive spines in the hippocampus of young and aged female rhesus monkeys. J Comp Neurol 465:540–550

    Article  CAS  PubMed  Google Scholar 

  • Harley CW, Malsbury CW, Squires A, Brown RA (2000) Testosterone decreases CA1 plasticity in vivo in gonadectomized male rats. Hippocampus 10:693–697

    Article  CAS  PubMed  Google Scholar 

  • Harooni HE, Naghdi N, Sepehri H, Rohani AH (2008) Intra hippocampal injection of testosterone impaired acquisition, consolidation and retrieval of inhibitory avoidance learning and memory in adult male rats. Behav Brain Res 188:71–77

    Article  CAS  PubMed  Google Scholar 

  • Harte-Hargrove LC, Varga-Wesson A, Duffy AM, Milner TA, Scharfman HE (2015) Opioid receptor-dependent sex differences in synaptic plasticity in the hippocampal mossy fiber pathway of the adult rat. J Neurosci 35:1723–1738

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hauser W, Hesdorffer D (1990) Epilepsy: frequency, causes and consequences. Epilepsy Foundation of America, Landover

    Google Scholar 

  • Hogervorst E, Bandelow S, Moffat SD (2005) Increasing testosterone levels and effects on cognitive functions in elderly men and women: a review. Curr Drug Targets CNS Neurol Disord 4:531–540

    Article  CAS  PubMed  Google Scholar 

  • Ishizuka N, Cowan WM, Amaral DG (1995) A quantitative analysis of the dendritic organization of pyramidal cells in the rat hippocampus. J Comp Neurol 362:17–45

    Article  CAS  PubMed  Google Scholar 

  • Jamadar RJ, Winters MJ, Maki PM (2012) Cognitive changes associated with ADT: a review of the literature. Asian J Androl 14:232–238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kellner Y, Godecke N, Dierkes T, Thieme N, Zagrebelsky M, Korte M (2014) The BDNF effects on dendritic spines of mature hippocampal neurons depend on neuronal activity. Front Synaptic Neurosci 6:5

    Article  PubMed  PubMed Central  Google Scholar 

  • Kesner RP (2007) Behavioral functions of the CA3 subregion of the hippocampus. Learn Mem 14:771–781

    Article  PubMed  Google Scholar 

  • Kole MH, Costoli T, Koolhaas JM, Fuchs E (2004) Bidirectional shift in the cornu ammonis 3 pyramidal dendritic organization following brief stress. Neuroscience 125:337–347

    Article  CAS  PubMed  Google Scholar 

  • Kolomeets NS, Orlovskaya DD, Uranova NA (2007) Decreased numerical density of CA3 hippocampal mossy fiber synapses in schizophrenia. Synapse 61:615–621

    Article  CAS  PubMed  Google Scholar 

  • Kossel AH, Williams CV, Schweizer M, Kater SB (1997) Afferent innervation influences the development of dendritic branches and spines via both activity-dependent and non-activity-dependent mechanisms. J Neurosci 17:6314–6324

    CAS  PubMed  Google Scholar 

  • Kovacs EG, MacLusky NJ, Leranth C (2003) Effects of testosterone on hippocampal CA1 spine synaptic density in the male rat are inhibited by fimbria/fornix transection. Neuroscience 122:807–810

    Article  CAS  PubMed  Google Scholar 

  • Kramar EA, Chen LY, Rex CS, Gall CM, Lynch G (2009) Estrogen’s place in the family of synaptic modulators. Mol Cell Pharmacol 1:258–262

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lazo OM, Gonzalez A, Ascano M, Kuruvilla R, Couve A, Bronfman FC (2013) BDNF regulates Rab11-mediated recycling endosome dynamics to induce dendritic branching. J Neurosci 33:6112–6122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leonard ST, Winsauer PJ (2011) The effects of gonadal hormones on learning and memory in male mammals: a review. Curr Zool 57:543–558

    Article  Google Scholar 

  • Leranth C, Shanabrough M, Horvath TL (2000) Hormonal regulation of hippocampal spine synapse density involves subcortical mediation. Neuroscience 101:349–356

    Article  CAS  PubMed  Google Scholar 

  • Leranth C, Shanabrough M, Redmond DE Jr (2002) Gonadal hormones are responsible for maintaining the integrity of spine synapses in the CA1 hippocampal subfield of female nonhuman primates. J Comp Neurol 447:34–42

    Article  CAS  PubMed  Google Scholar 

  • Leranth C, Petnehazy O, MacLusky NJ (2003) Gonadal hormones affect spine synaptic density in the CA1 hippocampal subfield of male rats. J Neurosci 23:1588–1592

    CAS  PubMed  Google Scholar 

  • Leranth C, Hajszan T, MacLusky NJ (2004a) Androgens increase spine synapse density in the CA1 hippocampal subfield of ovariectomized female rats. J Neurosci 24:495–499

    Article  CAS  PubMed  Google Scholar 

  • Leranth C, Prange-Kiel J, Frick KM, Horvath TL (2004b) Low CA1 spine synapse density is further reduced by castration in male non-human primates. Cereb Cortex 14:503–510

    Article  PubMed  Google Scholar 

  • Leranth C, Hajszan T, Szigeti-Buck K, Bober J, MacLusky NJ (2008) Bisphenol A prevents the synaptogenic response to estradiol in hippocampus and prefrontal cortex of ovariectomized nonhuman primates. Proc Natl Acad Sci USA 105:14187–14191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li M, Masugi-Tokita M, Takanami K, Yamada S, Kawata M (2012) Testosterone has sublayer-specific effects on dendritic spine maturation mediated by BDNF and PSD-95 in pyramidal neurons in the hippocampus CA1 area. Brain Res 1484:76–84

    Article  CAS  PubMed  Google Scholar 

  • Luine VN, Khylchevskaya RI, McEwen BS (1975) Effect of gonadal hormones on enzyme activities in brain and pituitary of male and female rats. Brain Res 86:283–292

    Article  CAS  PubMed  Google Scholar 

  • MacLusky NJ, Hajszan T, Leranth C (2004) Effects of dehydroepiandrosterone and flutamide on hippocampal CA1 spine synapse density in male and female rats: implications for the role of androgens in maintenance of hippocampal structure. Endocrinology 145:4154–4161

    Article  CAS  PubMed  Google Scholar 

  • Maki PM, Ernst M, London ED, Mordecai KL, Perschler P, Durso SC, Brandt J, Dobs A, Resnick SM (2007) Intramuscular testosterone treatment in elderly men: evidence of memory decline and altered brain function. J Clin Endocrinol Metab 92:4107–4114

    Article  CAS  PubMed  Google Scholar 

  • Matousek RH, Sherwin BB (2010) A randomized controlled trial of add-back estrogen or placebo on cognition in men with prostate cancer receiving an antiandrogen and a gonadotropin-releasing hormone analog. Psychoneuroendocrinology 35:215–225

    Article  CAS  PubMed  Google Scholar 

  • McLaughlin KJ, Wilson JO, Harman J, Wright RL, Wieczorek L, Gomez J, Korol DL, Conrad CD (2010) Chronic 17β-estradiol or cholesterol prevents stress-induced hippocampal CA3 dendritic retraction in ovariectomized female rats: possible correspondence between CA1 spine properties and spatial acquisition. Hippocampus 20:768–786

    CAS  PubMed  PubMed Central  Google Scholar 

  • Meitzen J, Grove DD, Mermelstein PG (2012) The organizational and aromatization hypotheses apply to rapid, nonclassical hormone action: neonatal masculinization eliminates rapid estradiol action in female hippocampal neurons. Endocrinology 153:4616–4621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mendell AL, Szigeti-Buck K, MacLusky NJ, Leranth C (2014) Orchidectomy does not significantly affect spine synapse density in the CA3 hippocampal subfield in St. Kitts vervet monkeys (Chlorocebus aethiops sabaeus). Neurosci Lett 559:189–192

    Article  CAS  PubMed  Google Scholar 

  • Meyer G, Ferres-Torres R, Mas M (1978) The effects of puberty and castration on hippocampal dendritic spines of mice. A Golgi study. Brain Res 155:108–112

    Article  CAS  PubMed  Google Scholar 

  • Milatovic D, Montine TJ, Zaja-Milatovic S, Madison JL, Bowman AB, Aschner M (2010) Morphometric analysis in neurodegenerative disorders. Curr Protoc Toxicol Chapter 12:Unit 12.16

  • Miller DI, Halpern DF (2014) The new science of cognitive sex differences. Trends Cogn Sci 18:37–45

    Article  PubMed  Google Scholar 

  • Naghdi N, Majlessi N, Bozorgmehr T (2005) The effect of intrahippocampal injection of testosterone enanthate (an androgen receptor agonist) and anisomycin (protein synthesis inhibitor) on spatial learning and memory in adult, male rats. Behav Brain Res 156:263–268

    Article  CAS  PubMed  Google Scholar 

  • Nelson CJ, Lee JS, Gamboa MC, Roth AJ (2008) Cognitive effects of hormone therapy in men with prostate cancer: a review. Cancer 113:1097–1106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, New York

    Google Scholar 

  • Phan A, Lancaster KE, Armstrong JN, MacLusky NJ, Choleris E (2011) Rapid effects of estrogen receptor alpha and beta selective agonists on learning and dendritic spines in female mice. Endocrinology 152:1492–1502

    Article  CAS  PubMed  Google Scholar 

  • Pierce JP, Kelter DT, McEwen BS, Waters EM, Milner TA (2014) Hippocampal mossy fiber leu-enkephalin immunoreactivity in female rats is significantly altered following both acute and chronic stress. J Chem Neuroanat 55:9–17

    Article  CAS  PubMed  Google Scholar 

  • Pope HG Jr, Kouri EM, Hudson JI (2000) Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: a randomized controlled trial. Arch Gen Psychiatry 57:133–140 (discussion 135-136)

    Article  CAS  PubMed  Google Scholar 

  • Reddy DS (2004) Testosterone modulation of seizure susceptibility is mediated by neurosteroids 3α-androstanediol and 17β-estradiol. Neuroscience 129:195–207

    Article  CAS  PubMed  Google Scholar 

  • Romeo RD, Staub D, Jasnow AM, Karatsoreos IN, Thornton JE, McEwen BS (2005) Dihydrotestosterone increases hippocampal N-methyl-d-aspartate binding but does not affect choline acetyltransferase cell number in the forebrain or choline transporter levels in the CA1 region of adult male rats. Endocrinology 146:2091–2097

    Article  CAS  PubMed  Google Scholar 

  • Sakia RM (1992) The Box–Cox transformation technique: a review. Statistician 41:169–178

    Article  Google Scholar 

  • Sarkey S, Azcoitia I, Garcia-Segura LM, Garcia-Ovejero D, DonCarlos LL (2008) Classical androgen receptors in non-classical sites in the brain. Horm Behav 53:753–764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scharfman HE (1994) Synchronization of area CA3 hippocampal pyramidal cells and non-granule cells of the dentate gyrus in bicuculline-treated rat hippocampal slices. Neuroscience 59:245–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scharfman HE, Chao MV (2013) The entorhinal cortex and neurotrophin signaling in Alzheimer’s disease and other disorders. Cogn Neurosci 4:123–135

    Article  PubMed  Google Scholar 

  • Scharfman HE, MacLusky NJ (2014a) Differential regulation of BDNF, synaptic plasticity and sprouting in the hippocampal mossy fiber pathway of male and female rats. Neuropharmacology 76 Pt C:696–708

    Article  PubMed  Google Scholar 

  • Scharfman HE, MacLusky NJ (2014b) Sex differences in the neurobiology of epilepsy: a preclinical perspective. Neurobiol Dis 72 Pt B:180–192

    Article  PubMed  Google Scholar 

  • Scharfman HE, Myers CE (2013) Hilar mossy cells of the dentate gyrus: a historical perspective. Front Neural Circuits 6:106

    Article  PubMed  PubMed Central  Google Scholar 

  • Scharfman HE, Mercurio TC, Goodman JH, Wilson MA, MacLusky NJ (2003) Hippocampal excitability increases during the estrous cycle in the rat: a potential role for brain-derived neurotrophic factor. J Neurosci 23:11641–11652

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sholl DA (1953) Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat 87:387–406

    CAS  PubMed  PubMed Central  Google Scholar 

  • Singh M, Meyer EM, Simpkins JW (1995) The effect of ovariectomy and estradiol replacement on brain-derived neurotrophic factor messenger ribonucleic acid expression in cortical and hippocampal brain regions of female Sprague–Dawley rats. Endocrinology 136:2320–2324

    CAS  PubMed  Google Scholar 

  • Skucas VA, Duffy AM, Harte-Hargrove LC, Magagna-Poveda A, Radman T, Chakraborty G, Schroeder CE, MacLusky NJ, Scharfman HE (2013) Testosterone depletion in adult male rats increases mossy fiber transmission, LTP, and sprouting in area CA3 of hippocampus. J Neurosci 33:2338–2355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith MD, Jones LS, Wilson MA (2002) Sex differences in hippocampal slice excitability: role of testosterone. Neuroscience 109:517–530

    Article  CAS  PubMed  Google Scholar 

  • Sohrabji F, Miranda RCG, Toran-Allerand CD (1995) Identification of a putative estrogen response element in the gene encoding brain-derived neurotrophic factor. Proc Natl Acad Sci USA 92:11110–11114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tabatadze N, Huang G, May RM, Jain A, Woolley CS (2015) Sex differences in molecular signaling at inhibitory synapses in the hippocampus. J Neurosci 35:11252–11265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tabori NE, Stewart LS, Znamensky V, Romeo RD, Alves SE, McEwen BS, Milner TA (2005) Ultrastructural evidence that androgen receptors are located at extranuclear sites in the rat hippocampal formation. Neuroscience 130:151–163

    Article  CAS  PubMed  Google Scholar 

  • Takemoto-Kimura S, Ageta-Ishihara N, Nonaka M, Adachi-Morishima A, Mano T, Okamura M, Fujii H, Fuse T, Hoshino M, Suzuki S, Kojima M, Mishina M, Okuno H, Bito H (2007) Regulation of dendritogenesis via a lipid-raft-associated Ca2+/calmodulin-dependent protein kinase CLICK-III/CaMKIgamma. Neuron 54:755–770

    Article  CAS  PubMed  Google Scholar 

  • Tamura M, Tamura N, Ikeda T, Koyama R, Ikegaya Y, Matsuki N, Yamada MK (2009) Influence of brain-derived neurotrophic factor on pathfinding of dentate granule cell axons, the hippocampal mossy fibers. Mol Brain 2:2

    Article  PubMed  PubMed Central  Google Scholar 

  • Witter MP (2007) Intrinsic and extrinsic wiring of CA3: indications for connectional heterogeneity. Learn Mem 14:705–713

    Article  PubMed  Google Scholar 

  • Woolley CS, Gould E, Frankfurt M, McEwen BS (1990) Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. J Neurosci 10:4035–4039

    CAS  PubMed  Google Scholar 

  • Yeap BB (2009) Testosterone and ill-health in aging men. Nat Clin Pract Endocrinol Metab 5:113–121

    Article  CAS  PubMed  Google Scholar 

  • Young LA, Neiss MB, Samuels MH, Roselli CE, Janowsky JS (2010) Cognition is not modified by large but temporary changes in sex hormones in men. J Clin Endocrinol Metab 95:280–288

    Article  CAS  PubMed  Google Scholar 

  • Zuloaga DG, Puts DA, Jordan CL, Breedlove SM (2008) The role of androgen receptors in the masculinization of brain and behavior: what we’ve learned from the testicular feminization mutation. Horm Behav 53:613–626

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Supported by NSERC Discovery Grants to NJM and CDCB and R01 NS 37562 from the National Institutes of Health (USA) to HES. ALM was the recipient of an Ontario Graduate Studentship during these studies.

Author information

Author notes

  1. Dan McCloskey

    Present address: Department of Psychology, College of Staten Island, City University of New York, New York, 10314, USA

Authors and Affiliations

  1. Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, N1G 2W1, Canada

    Ari L. Mendell, Sarah Atwi, Craig D. C. Bailey & Neil J. MacLusky

  2. Nathan Kline Institute for Psychiatric Research, Center of Dementia Research, Orangeburg, NY, 10962, USA

    Dan McCloskey & Helen E. Scharfman

  3. Department of Child and Adolescent Psychiatry, New York University Langone Medical Center, New York, NY, 10016, USA

    Dan McCloskey & Helen E. Scharfman

  4. Department of Physiology and Neuroscience, New York University Langone Medical Center, New York, NY, 10016, USA

    Dan McCloskey & Helen E. Scharfman

  5. Department of Psychiatry, New York University Langone Medical Center, New York, NY, 10016, USA

    Dan McCloskey & Helen E. Scharfman

Authors
  1. Ari L. Mendell
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sarah Atwi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Craig D. C. Bailey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dan McCloskey
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Helen E. Scharfman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Neil J. MacLusky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neil J. MacLusky.

Ethics declarations

Conflict of interest

Ari Mendell, Sarah Atwi, Craig Bailey, Dan McCloskey, Helen Scharfman and Neil MacLusky report no biomedical financial interests or potential conflicts of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mendell, A.L., Atwi, S., Bailey, C.D.C. et al. Expansion of mossy fibers and CA3 apical dendritic length accompanies the fall in dendritic spine density after gonadectomy in male, but not female, rats. Brain Struct Funct 222, 587–601 (2017). https://doi.org/10.1007/s00429-016-1237-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-016-1237-6

Keywords

Search

Navigation