Skip to main content

Advertisement

SpringerLink
Log in

Structural aspects of the aging invertebrate brain

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Aging is characterized by a decline in neuronal function in all animal species investigated so far. Functional changes are accompanied by and may be in part caused by, structurally visible degenerative changes in neurons. In the mammalian brain, normal aging shows abnormalities in dendrites and axons, as well as ultrastructural changes in synapses, rather than global neuron loss. The analysis of the structural features of aging neurons, as well as their causal link to molecular mechanisms on the one hand, and the functional decline on the other hand is crucial in order to understand the aging process in the brain. Invertebrate model organisms like Drosophila and C. elegans offer the opportunity to apply a forward genetic approach to the analysis of aging. In the present review, we aim to summarize findings concerning abnormalities in morphology and ultrastructure in invertebrate brains during normal aging and compare them to what is known for the mammalian brain. It becomes clear that despite of their considerably shorter life span, invertebrates display several age-related changes very similar to the mammalian condition, including the retraction of dendritic and axonal branches at specific locations, changes in synaptic density and increased accumulation of presynaptic protein complexes. We anticipate that continued research efforts in invertebrate systems will significantly contribute to reveal (and possibly manipulate) the molecular/cellular pathways leading to neuronal aging in the mammalian brain.

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

Similar content being viewed by others

References

  • Akhmedov K, Rizzo V, Kadakkuzha BM et al (2013) Decreased response to acetylcholine during aging of aplysia neuron R15. PLoS ONE 8:e84793

    PubMed  PubMed Central  Google Scholar 

  • Alexander AG, Marfil V, Li C (2014) Use of C. elegans as a model to study Alzheimer’s disease and other neurodegenerative diseases. Front Genet 5:1–21

    CAS  Google Scholar 

  • Alvarez J, Alvarez-Illera P, García-Casas P et al (2020) The role of Ca2+ signaling in aging and neurodegeneration: insights from Caenorhabditis elegans models. Cells 9:204

    CAS  PubMed Central  Google Scholar 

  • Amdam GV (2011) Social context, stress, and plasticity of aging. Aging Cell 10:18–27

    CAS  PubMed  Google Scholar 

  • Atkins G, Pollack GS (1986) Age-dependent occurrence of an ascending axon on the omega neuron of the cricket, Teleogryllus oceanicus. J Comp Neurol 243:527–534

    CAS  PubMed  Google Scholar 

  • Augustin H, Partridge L (2009) Invertebrate models of age-related muscle degeneration. Biochim Biophys Acta 1790:1084–1094

    CAS  PubMed  Google Scholar 

  • Ball MJ (1977) Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. Acta Neuropathol 37:111–118

    CAS  PubMed  Google Scholar 

  • Bancher C, Lassmann H, Budka H et al (1987) Neurofibrillary tangles in Alzheimer’s disease and progressive supranuclear palsy: antigenic similarities and differences. Acta Neuropathol 74:39–46

    CAS  PubMed  Google Scholar 

  • Beckingham KM, Texada MJ, Baker DA et al (2005) Genetics of graviperception in animals. Adv Genet 55:105–145

    CAS  PubMed  Google Scholar 

  • Behrends A, Scheiner R, Baker N, Amdam GV (2007) Cognitive aging is linked to social role in honey bees (Apis mellifera). Exp Gerontol 42:1146–1153

    PubMed  PubMed Central  Google Scholar 

  • Bellanger C, Halm M-P, Dauphin F, Chichery R (2005) In vitro evidence and age-related changes for nicotinic but not muscarinic acetylcholine receptors in the central nervous system of Sepia officinalis. Neurosci Lett 387:162–167

    CAS  PubMed  Google Scholar 

  • Beramendi A, Peron S, Casanova G et al (2007) Neuromuscular junction in abdominal muscles of Drosophila melanogaster during adulthood and aging. J Comp Neurol 501:498–508

    PubMed  Google Scholar 

  • Bhukel A, Beuschel CB, Maglione M et al (2019) Autophagy within the mushroom body protects from synapse aging in a non-cell autonomous manner. Nat Commun 10:1–13

    CAS  Google Scholar 

  • Bishop NA, Lu T, Yankner BA (2010) Neural mechanisms of ageing and cognitive decline. Nature 464:529–535

    CAS  PubMed  PubMed Central  Google Scholar 

  • Blackwell K, Sewell AK, Wu Z, Han M (2019) TOR signaling in caenorhabditis elegans development, metabolism, and aging. Genetics 213:329–360

    CAS  PubMed  PubMed Central  Google Scholar 

  • Blalock EM, Chen KC, Sharrow K et al (2003) Gene microarrays in hippocampal aging: statistical profiling identifies novel processes correlated with cognitive impairment. J Neurosci 23:3807–3819

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bonini NM, Fortini ME (2003) Human neurodegenerative disease modeling using Drosophila. Annu Rev Neurosci 26:627–656

    CAS  PubMed  Google Scholar 

  • Bowley MP, Cabral H, Rosene DL, Peters A (2010) Age changes in myelinated nerve fibers of the cingulate bundle and corpus callosum in the rhesus monkey. J Comp Neurol 518:3046–3064

    PubMed  PubMed Central  Google Scholar 

  • Brizzee KR, Knox C (1980) The aging process in the neuron. Adv Exp Med Biol 129:71–98

    CAS  PubMed  Google Scholar 

  • Brody H (1955) Organization of the cerebral cortex. III. A study of aging in the human cerebral cortex. J Comp Neurol 102:511–516

    CAS  PubMed  Google Scholar 

  • Brown S, Strausfeld N (2009) The effect of age on a visual learning task in the American cockroach. Learn Mem 16:210–223

    PubMed  Google Scholar 

  • Brunk U, Brun A (1972) The effect of aging on lysosomal permeability in nerve cells of the central nervous system. An enzyme histochemical study in rat. Histochemie 30:315–324

    CAS  PubMed  Google Scholar 

  • Budelmann BU (1995) The cephalopod nervous system: what evolution has made of the molluscan design. In: The Nervous System of Invertebrates. pp 115–138

  • Burke SN, Barnes CA (2006) Neural plasticity in the ageing brain. Nat Rev Neurosci 7:30–40

    CAS  PubMed  Google Scholar 

  • Calahorro F, Ruiz-Rubio M (2011) Caenorhabditis elegans as an experimental tool for the study of complex neurological diseases: Parkinson’s disease, Alzheimer’s disease and autism spectrum disorder. Invert Neurosci 11:73–83

    PubMed  Google Scholar 

  • Calì C, Wawrzyniak M, Becker C et al (2018) The effects of aging on neuropil structure in mouse somatosensory cortex - a 3D electron microscopy analysis of layer 1. PLoS ONE 13:1–21

    Google Scholar 

  • Carbone MA, Yamamoto A, Huang W et al (2016) Genetic architecture of natural variation in visual senescence in Drosophila. Proc Natl Acad Sci U S A 113:E6620–E6629

    CAS  PubMed  PubMed Central  Google Scholar 

  • Castelli V, Benedetti E, Antonosante A et al (2019) Neuronal cells rearrangement during aging and neurodegenerative disease: metabolism, oxidative stress and organelles dynamic. Front Mol Neurosci 12:1–13

    Google Scholar 

  • Chen CH, Chen YC, Jiang HC et al (2013) Neuronal aging: learning from C. elegans. J Mol Signal 8:1–10

    CAS  Google Scholar 

  • Chew YL, Fan X, Götz J, Nicholas HR (2013) PTL-1 regulates neuronal integrity and lifespan in C. elegans. J Cell Sci 126:2079–2091

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chichery MP, Chichery R (1992) Behavioural and neurohistological changes in aging Sepia. Brain Res 574:77–84

    CAS  PubMed  Google Scholar 

  • Coleman PD, Flood DG (1987) Neuron numbers and dendritic extent in normal aging and Alzheimer’s disease. Neurobiol Aging 8:521–545

    CAS  PubMed  Google Scholar 

  • Cooper JF, Van Raamsdonk JM (2018) Modeling Parkinson’s disease in C. elegans. J Parkinsons Dis 8:17–32

    CAS  PubMed  PubMed Central  Google Scholar 

  • Corfas G, Dudai Y (1991) Morphology of a sensory neuron in Drosophila is abnormal in memory mutants and changes during aging. Proc Natl Acad Sci U S A 88:7252–7256

    CAS  PubMed  PubMed Central  Google Scholar 

  • Coss RG, Brandon JG, Globus A (1980) Changes in morphology of dendritic spines on honeybee calycal interneurons associated with cumulative nursing and foraging experiences. Brain Res 192:49–59

    CAS  PubMed  Google Scholar 

  • Cupp C, Uemura E (1980) Age-related changes in prefrontal cortex of Macaca mulatta: quantitative analysis of dendritic branching patterns. Exp Neurol 69:143–163

    CAS  PubMed  Google Scholar 

  • Dall KB, Færgeman NJ (2019) Metabolic regulation of lifespan from a C. Elegans perspective. Genes Nutr 14:1–12

    CAS  Google Scholar 

  • Daniele S, Giacomelli C, C. M (2018) Brain ageing and neurodegenerative disease: the role of cellular waste management. Biochem Pharmacol 158:207–216

    CAS  PubMed  Google Scholar 

  • Davie K, Janssens J, Koldere D et al (2018) A single-cell transcriptome atlas of the aging Drosophila brain. Cell 174:982–998

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dickstein D, Weaver C, Luebke J, Hof P (2013) Dendritic spine changes associated with normal aging. Neuroscience 251:21–32

    CAS  PubMed  Google Scholar 

  • Donev R, Kolev M, Millet B, Thome J (2009) Neuronal death in Alzheimer’s disease and therapeutic opportunities. J Cell Mol Med 13:4329–4348

    CAS  PubMed  PubMed Central  Google Scholar 

  • Double KL, Dedov VN, Fedorow H et al (2008) The comparative biology of neuromelanin and lipofuscin in the human brain. Cell Mol Life Sci 65:1669–1682

    CAS  PubMed  Google Scholar 

  • Driver C, Georgiou A, Georgiou G (2004) The contribution by mitochondrially induced oxidative damage to aging in Drosophila melanogaster. Biogerontology 5:185–192

    CAS  PubMed  Google Scholar 

  • Dudas SP, Arking R (1995) A coordinate upregulation of antioxidant gene activities is associated with the delayed onset of senescence in a long-lived strain of Drosophila. J Gerontol A Biol Sci Med Sci 50:B117–B127

    CAS  PubMed  Google Scholar 

  • Dumitriu D, Hao J, Hara Y et al (2010) Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment. J Neurosci 30:7507–7515

    CAS  PubMed  PubMed Central  Google Scholar 

  • Eavri R, Shepherd J, Welsh CA et al (2018) Interneuron simplification and loss of structural plasticity as markers of aging-related functional decline. J Neurosci 38:8421–8432

    CAS  PubMed  PubMed Central  Google Scholar 

  • Farnsworth DR, Bayraktar OA, Doe CQ (2015) Aging neural progenitors lose competence to respond to mitogenic Notch signaling. Curr Biol 25:3058–3068

    CAS  PubMed  PubMed Central  Google Scholar 

  • Flood DG, Coleman PD (1993) Dendritic regression dissociated from neuronal death but associated with partial deafferentation in aging rat supraoptic nucleus. Neurobiol Aging 14:575–587

    CAS  PubMed  Google Scholar 

  • Flurkey K, Currer JM, Harrison DE (2007) The mouse in biomedical research. In: James G. Fox (ed) American College of Laboratory Animal Medicine series. Elsevier, AP: Amsterdam; Boston

  • Foster T (2019) Senescent neurophysiology: Ca2+ signaling from the membrane to the nucleus. Neurobiol Learn Mem 164:107064

    CAS  PubMed  PubMed Central  Google Scholar 

  • Freeman SH, Kandel R, Cruz L et al (2008) Preservation of neuronal number despite age-related cortical brain atrophy in elderly subjects without Alzheimer disease. J Neuropathol Exp Neurol 67:1205–1212

    PubMed  Google Scholar 

  • Frolkis VV, Stupina AS, Martinenko OA et al (1984) Aging of neurons in the mollusc Lymnaea stagnalis. Structure, function and sensitivity to transmitters. Mech Ageing Dev 25:91–102

    CAS  PubMed  Google Scholar 

  • Gaeta AL, Caldwell KA, Caldwell GA (2019) Found in translation: the utility of C. elegans alpha-synuclein models of Parkinson’s disease. Brain Sci 9:1–15

    Google Scholar 

  • Gao A, Uit de Bos J, Sterken M et al (2018) Forward and reverse genetics approaches to uncover metabolic aging pathways in Caenorhabditis elegans. Biochim Biophys Acta Mol Basis Dis 1864:2697–2706

    CAS  PubMed  Google Scholar 

  • Gazzaley AH, Thakker MM, Hof PR, Morrison JH (1997) Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys. Neurobiol Aging 18:549–553

    CAS  PubMed  Google Scholar 

  • Gehring KB, Heufelder K, Depner H et al (2017) Age-associated increase of the active zone protein Bruchpilot within the honeybee mushroom body. PLoS ONE 12:1–19

    Google Scholar 

  • Gilissen EP, Staneva-Dobrovski L (2013) Distinct types of lipofuscin pigment in the hippocampus and cerebellum of aged cheirogaleid primates. Anat Rec (Hoboken) 296:1895–1906

    CAS  Google Scholar 

  • Goodman L, Bonini N (2020) New roles for canonical transcription factors in repeat expansion diseases. Trends Genet 36:81–92

    CAS  PubMed  Google Scholar 

  • Goodman M, Hall D, Avery L, Lockery S (1998) Active currents regulate sensitivity and dynamic range in C. elegans neurons. Neuron 20:763–772

    CAS  PubMed  PubMed Central  Google Scholar 

  • Greeve I, Kretzschmar D, Tschäpe J-A et al (2004) Age-dependent neurodegeneration and Alzheimer-amyloid plaque formation in transgenic Drosophila. J Neurosci 24:3899–3906

    CAS  PubMed  PubMed Central  Google Scholar 

  • Grill JD, Riddle DR (2002) Age-related and laminar-specific dendritic changes in the medial frontal cortex of the rat. Brain Res 937:8–21

    CAS  PubMed  Google Scholar 

  • Groh C, Lu Z, Meinertzhagen IA, Rössler W (2012) Age-related plasticity in the synaptic ultrastructure of neurons in the mushroom body calyx of the adult honeybee Apis mellifera. J Comp Neurol 520:3509–3527

    PubMed  Google Scholar 

  • Groh C, Tautz J, Rössler W (2004) Synaptic organization in the adult honey bee brain is influenced by brood-temperature control during pupal development. Proc Natl Acad Sci U S A 101:4268–4273

    CAS  PubMed  PubMed Central  Google Scholar 

  • Grundke-Iqbal I, Vorbrodt AW, Iqbal K et al (1988) Microtubule-associated polypeptides tau are altered in Alzheimer paired helical filaments. Mol Brain Res 4:43–52

    CAS  Google Scholar 

  • Gupta VK, Pech U, Bhukel A et al (2016) Spermidine Suppresses age-associated memory impairment by preventing adverse increase of presynaptic active zone size and release. PLoS Biol 14:e1002563

    PubMed  PubMed Central  Google Scholar 

  • Guven-Ozkan T, Davis RL (2014) Functional neuroanatomy of Drosophila olfactory memory formation. Learn Mem 21:519–526

    PubMed  PubMed Central  Google Scholar 

  • Haddadi M, Jahromi SR, Sagar BKC et al (2014) Brain aging, memory impairment and oxidative stress: a study in Drosophila melanogaster. Behav Brain Res 259:60–69

    CAS  PubMed  Google Scholar 

  • Hall H, Medina P, Cooper DA et al (2017) Transcriptome profiling of aging Drosophila photoreceptors reveals gene expression trends that correlate with visual senescence. BMC Genomics 18:894

    PubMed  PubMed Central  Google Scholar 

  • Hartline DK (2011) The evolutionary origins of glia. Glia 59:1215–1236

    PubMed  Google Scholar 

  • Hartline DK, Colman DR (2007) Rapid conduction and the evolution of giant axons and myelinated fibers. Curr Biol 17:29–35

    Google Scholar 

  • Hendy R (1971) Electron microscopy of lipofuscin pigment stained by the Schmörl and Fontana techniques. Histochemie 26:311–318

    CAS  PubMed  Google Scholar 

  • Herman MM, Miquel J, Johnson M (1971) Insect brain as a model for the study of aging. Acta Neuropathol 19:167–183

    CAS  PubMed  Google Scholar 

  • Herndon L, Schmeissner P, Dudaronek J et al (2002) Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature 419:808–814

    CAS  PubMed  Google Scholar 

  • Hess M, Gomariz A, Goksel O, Ewald CY (2019) In-vivo quantitative image analysis of age-related morphological changes of C. elegans neurons reveals a correlation between neurite bending and novel neurite outgrowths. eNeuro 6:1–13

  • Humphries MA, Mustard JA, Hunter SJ et al (2003) Invertebrate D2 type dopamine receptor exhibits age-based plasticity of expression in the mushroom bodies of the honeybee brain. J Neurobiol 55:315–330

    CAS  PubMed  Google Scholar 

  • Hussain A, Pooryasin A, Zhang M et al (2018) Inhibition of oxidative stress in cholinergic projection neurons fully rescues aging-associated olfactory circuit degeneration in drosophila. Elife 7:1–20

    Google Scholar 

  • Iijima K, Iijima-Ando K (2008) Drosophila models of Alzheimer’s amyloidosis: the challenge of dissecting the complex mechanisms of toxicity of amyloid-beta 42. J Alzheimers Dis 15:523–540

    CAS  PubMed  Google Scholar 

  • Iijima K, Liu HP, Chiang AS et al (2004) Dissecting the pathological effects of human Aβ40 and Aβ42 in Drosophila: a potential model for Alzheimer’s disease. Proc Natl Acad Sci U S A 101:6623–6628

    CAS  PubMed  PubMed Central  Google Scholar 

  • Janse C, Peretz B, van der Roest M, Dubelaar EJ (1999) Excitability and branching of neuroendocrine cells during reproductive senescence. Neurobiol Aging 20:675–683

    CAS  PubMed  Google Scholar 

  • Janse C, van der Roest M, Jansen RF et al (1996) Atrophy and degeneration of peptidergic neurons and cessation of egg laying in the aging pond snail Lymnaea stagnalis. J Neurobiol 29:202–212

    CAS  PubMed  Google Scholar 

  • Jenett A, Rubin GM, Ngo TTB et al (2012) A GAL4-driver line resource for Drosophila neurobiology. Cell Rep 2:991–1001. https://doi.org/10.1016/j.celrep.2012.09.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson JR, Jenn RC, Barclay JW et al (2010) Caenorhabditis elegans: a useful tool to decipher neurodegenerative pathways. Biochem Soc Trans 38:559–563

    CAS  PubMed  Google Scholar 

  • Kempsell AT, Fieber LA (2014) Behavioral aging is associated with reduced sensory neuron excitability in Aplysia californica. Front Aging Neurosci 6:84

    PubMed  PubMed Central  Google Scholar 

  • Kempsell AT, Fieber LA (2015) Aging in sensory and motor neurons results in learning failure in Aplysia californica. PLoS ONE 10:e0127056

    PubMed  PubMed Central  Google Scholar 

  • Keuker JIH, Luiten PGM, Fuchs E (2003) Preservation of hippocampal neuron numbers in aged rhesus monkeys. Neurobiol Aging 24:157–165

    PubMed  Google Scholar 

  • Kim D-K, Kim TH, Lee S-J (2016) Mechanisms of aging-related proteinopathies in Caenorhabditis elegans. Exp Mol Med 48:e263

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kounatidis I, Chtarbanova S, Cao Y et al (2017) NF-κB immunity in the brain determines fly lifespan in healthy aging and age-related neurodegeneration. Cell Rep 19:836–848

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kretzschmar D (2005) Neurodegenerative mutants in Drosophila: a means to identify genes and mechanisms involved in human diseases? Invert Neurosci 5:97–109

    CAS  PubMed  Google Scholar 

  • Li J, Le W (2013) Modeling neurodegenerative diseases in Caenorhabditis elegans. Exp Neurol 250:94–103

    CAS  PubMed  Google Scholar 

  • Li W, Prazak L, Chatterjee N et al (2013) Activation of transposable elements during aging and neuronal decline in Drosophila. Nat Neurosci 16:529–531

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liang YT, Sigrist S (2018) Autophagy and proteostasis in the control of synapse aging and disease. Curr Opin Neurobiol 48:113–121

    CAS  PubMed  Google Scholar 

  • Liao S, Broughton S, Nässel DR (2017) Behavioral senescence and aging-related changes in motor neurons and brain neuromodulator levels are ameliorated by lifespan-extending reproductive dormancy in Drosophila. Front Cell Neurosci 11:1–20

    CAS  Google Scholar 

  • Ling D, Magallanes M, Salvaterra PM (2014) Accumulation of amyloid-like Aβ1-42 in AEL (autophagy-endosomal-lysosomal) vesicles: potential implications for plaque biogenesis. ASN Neuro 6:95–109

    Google Scholar 

  • Ling D, Salvaterra P (2011) Brain aging and 1 neurotoxicity converge via deterioration in autophagy-lysosomal system: a conditional Drosophila model linking Alzheimer’s neurodegeneration with aging. Acta Neuropathol 121:183–191

    PubMed  Google Scholar 

  • Ling D, Salvaterra PM (2009) A central role for autophagy in Alzheimer-type neurodegeneration. Autophagy 5:738–740

    CAS  PubMed  Google Scholar 

  • Lipinski M, Bin Z, Lu T et al (2010) Genome-wide analysis reveals mechanisms modulating autophagy in normal brain aging and in Alzheimer’s disease. Proc Natl Acad Sci U S A 107:14164–14169

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu J, Zhang B, Lei H et al (2013) Functional aging in the nervous system contributes to age-dependent motor activity decline in C. elegans. Cell Metab 18:392–402

    CAS  PubMed  Google Scholar 

  • Liu Q, Kidd PB, Dobosiewicz M, Bargmann CI (2018) C. elegans AWA olfactory neurons fire calcium-mediated all-or-none action potentials. Cell 175:57-70.e17

    CAS  PubMed  Google Scholar 

  • Lockery SR, Goodman MB (2009) The quest for action potentials in C. elegans neurons hits a plateau. Nat Neurosci 12:377–378. https://doi.org/10.1038/nn0409-377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loerch PM, Lu T, Dakin KA et al (2008) Evolution of the aging brain transcriptome and synaptic regulation. PLoS ONE 3:e3329

    PubMed  PubMed Central  Google Scholar 

  • Lu T, Pan Y, Kao S et al (2004) Gene regulation and DNA damage in the ageing human brain. Nature 429:883–891

    CAS  PubMed  Google Scholar 

  • Lublin A, Link C (2013) Alzheimer’s disease drug discovery: in vivo screening using Caenorhabditis elegans as a model for β-amyloid peptide-induced toxicity. Drug Discov Today Technol 10:e115–e119

    CAS  PubMed  Google Scholar 

  • Marner L, Nyengaard JR, Tang Y, Pakkenberg B (2003) Marked loss of myelinated nerve fibers in the human brain with age. J Comp Neurol 462:144–152

    PubMed  Google Scholar 

  • Masliah E, Mallory M, Hansen L et al (1993) Quantitative synaptic alterations in the human neocortex during normal aging. Neurology 43:192–197

    CAS  PubMed  Google Scholar 

  • Maulik M, Mitra S, Bult-Ito A et al (2017) Behavioral phenotyping and pathological indicators of Parkinson’s disease in C. elegans models. Front Genet 8:1–21

    Google Scholar 

  • McGurk L, Berson A, Bonini N (2015) Drosophila as an in vivo model for human neurodegenerative disease. Genetics 201:377–402

    CAS  PubMed  PubMed Central  Google Scholar 

  • Merrill DA, Chiba AA, Tuszynski MH (2001) Conservation of neuronal number and size in the entorhinal cortex of behaviorally characterized aged rats. J Comp Neurol 438:445–456

    CAS  PubMed  Google Scholar 

  • Merrill DA, Roberts JA, Tuszynski MH (2000) Conservation of neuron number and size in entorhinal cortex layers II, III, and V/VI of aged primates. J Comp Neurol 422:396–401

    CAS  PubMed  Google Scholar 

  • Mohammed HA, Santer RM (2001) Total neuronal numbers of rat lumbosacral primary afferent neurons do not change with age. Neurosci Lett 304:149–152

    CAS  PubMed  Google Scholar 

  • Moreno-García A, Kun A, Calero O et al (2018) An overview of the role of lipofuscin in age-related neurodegeneration. Front Neurosci 12:1–13

    Google Scholar 

  • Morrison JH, Hof PR (1997) Life and death of neurons in the aging brain. Science 278:412–419

    CAS  PubMed  Google Scholar 

  • Mostany R, Anstey JE, Crump KL et al (2013) Altered synaptic dynamics during normal brain aging. J Neurosci 33:4094–4104

    CAS  PubMed  PubMed Central  Google Scholar 

  • Muller F, Lustgarten M, Jang Y et al (2007) Trends in oxidative aging theories. Free Radic Biol Med 15:477–503

    Google Scholar 

  • Münch D, Kreibich CD, Amdam GV (2013) Aging and its modulation in a long-lived worker caste of the honey bee. J Exp Biol 216:1638–1649

    PubMed  PubMed Central  Google Scholar 

  • Nakamura S, Akiguchi I, Kameyama M, Mizuno N (1985) Age-related changes of pyramidal cell basal dendrites in layers III and V of human motor cortex: a quantitative Golgi study. Acta Neuropathol 65:281–284

    CAS  PubMed  Google Scholar 

  • Nash TR, Chow ES, Law AD, et al (2019) Daily blue-light exposure shortens lifespan and causes brain neurodegeneration in Drosophila. npj Aging Mech Dis 5:1–8

  • Neuser K, Triphan T, Mronz M et al (2008) Analysis of a spatial orientation memory in Drosophila. Nature 453:1244–1247

    CAS  PubMed  Google Scholar 

  • Niikura T, Tajima H, Kita Y (2006) Neuronal cell death in Alzheimers disease and a neuroprotective factor, humanin. Curr Neuropharmacol 4:139–147

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nikoletopoulou V, Tavernarakis N (2012) Calcium homeostasis in aging neurons. Front Genet 3:1–17

    Google Scholar 

  • Omoto JJ, Nguyen BCM, Kandimalla P et al (2018) Neuronal constituents and putative interactions within the drosophila ellipsoid body neuropil. Front Neural Circuits 12:1–26

    Google Scholar 

  • Page T, Einstein M, Duan H et al (2002) Morphological alterations in neurons forming corticocortical projections in the neocortex of aged Patas monkeys. Neurosci Lett 317:37–41

    CAS  PubMed  Google Scholar 

  • Pakkenberg B, Gundersen HJ (1997) Neocortical neuron number in humans: effect of sex and age. J Comp Neurol 384:312–320. https://doi.org/10.1073/pnas.0803652105

    Article  PubMed  Google Scholar 

  • Pan C-L, Peng C-Y, Chen C-H, McIntire S (2011) Genetic analysis of age-dependent defects of the Caenorhabditis elegans touch receptor neurons. Proc Natl Acad Sci 108:9274–9279

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pannese E (2011) Morphological changes in nerve cells during normal aging. Brain Struct Funct 216:85–89

    PubMed  Google Scholar 

  • Peretz B, Romanenko A, Markesbery W (1984) Functional history of two motor neurons and the morphometry of their neuromuscular junctions in the gill of Aplysia: evidence for differential aging. Proc Natl Acad Sci U S A 81:4232–4236

    CAS  PubMed  PubMed Central  Google Scholar 

  • Perisse E, Burke C, Huetteroth W, Waddell S (2013) Shocking revelations and saccharin sweetness review in the study of Drosophila olfactory memory. Curr Biol 23:752–763

    Google Scholar 

  • Peters A (1994) The organization of the primary visual cortex in the macaque BT - primary visual cortex in primates. In: Peters A, Rockland KS (eds) Springer. US, Boston, MA, pp 1–35

    Google Scholar 

  • Peters A, Rosene DL (2003) In aging, is it gray or white? J Comp Neurol 462:139–143

    PubMed  Google Scholar 

  • Peters A, Sethares C (2002) Aging and the myelinated fibers in prefrontal cortex and corpus callosum of the monkey. J Comp Neurol 442:277–291

    PubMed  Google Scholar 

  • Peters A, Sethares C, Luebke JI (2008) Synapses are lost during aging in the primate prefrontal cortex. Neuroscience 152:970–981

    CAS  PubMed  Google Scholar 

  • Petralia RS, Mattson MP, Yao PJ (2014) Communication breakdown: the impact of ageing on synapse structure. Ageing Res Rev 14:31–42

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pir GJ, Choudhary B, Mandelkow E (2017) Caenorhabditis elegans models of tauopathy. FASEB J 31:5137–5148

    CAS  PubMed  Google Scholar 

  • Pyapali GK, Turner DA (1996) Increased dendritic extent in hippocampal CA1 neurons from aged F344 rats. Neurobiol Aging 17:601–611

    CAS  PubMed  Google Scholar 

  • Rapp PR, Gallagher M (1996) Preserved neuron number in the hippocampus of aged rats with spatial learning deficits. Proc Natl Acad Sci U S A 93:9926–9930

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rasmussen T, Schliemann T, Sorensen JC et al (1996) Memory impaired aged rats: no loss of principal hippocampal and subicular neurons. Neurobiol Aging 17:143–147

    CAS  PubMed  Google Scholar 

  • Remolina SC, Hafez DM, Robinson GE, Hughes KA (2007) Senescence in the worker honey bee Apis mellifera. J Insect Physiol 53:1027–1033

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rera M, Clark RI, Walker DW (2012) Intestinal barrier dysfunction links metabolic and inflammatory markers of aging to death in Drosophila. Proc Natl Acad Sci U S A 109:21528–21533

    CAS  PubMed  PubMed Central  Google Scholar 

  • Richard MB, Taylor SR, Greer CA (2010) Age-induced disruption of selective olfactory bulb synaptic circuits. Proc Natl Acad Sci 107:15613–15618

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rössler W, Brill M (2013) Parallel processing in the honeybee olfactory pathway: structure, function, and evolution. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 199:981–996

    PubMed  PubMed Central  Google Scholar 

  • Rubinsztein DC, Mariño G, Kroemer G (2011) Autophagy and aging. Cell 146:682–695

    CAS  PubMed  Google Scholar 

  • Salvadores N, Sanhueza M, Manque P, Court FA (2017) Axonal degeneration during aging and its functional role in neurodegenerative disorders. Front Neurosci 11:451

    PubMed  PubMed Central  Google Scholar 

  • Sasagawa H, Narita R, Kitagawa Y, Kadowaki T (2003) The expression of genes encoding visual components is regulated by a circadian clock, light environment and age in the honeybee (Apis mellifera). Eur J Neurosci 17:963–970

    PubMed  Google Scholar 

  • Seehuus S-C, Krekling T, Amdam GV (2006) Cellular senescence in honey bee brain is largely independent of chronological age. Exp Gerontol 41:1117–1125

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shaye DD, Greenwald I (2011) OrthoList: a compendium of C. elegans genes with human orthologs. PLoS One 6:e20085

  • Shibata M, Lu T, Furuya T et al (2006) Regulation of intracellular accumulation of mutant huntingtin by beclin 1. J Biol Chem 281:14474–14485

    CAS  PubMed  Google Scholar 

  • Simcock NK, Wakeling LA, Ford D, Wright GA (2017) Effects of age and nutritional state on the expression of gustatory receptors in the honeybee (Apis mellifera). PLoS ONE 12:e0175158

    PubMed  PubMed Central  Google Scholar 

  • Son HG, Altintas O, Kim EJE et al (2019) Age-dependent changes and biomarkers of aging in Caenorhabditis elegans. Aging Cell 18:1–11

    Google Scholar 

  • Tamura T, Chiang AS, Ito N et al (2003) Aging specifically impairs amnesiac-dependent memory in Drosophila. Neuron 40:1003–1011

    CAS  PubMed  Google Scholar 

  • Tank EMH, Rodgers KE, Kenyon C (2011) Spontaneous age-related neurite branching in Caenorhabditis elegans. J Neurosci 31:9279–9288

    CAS  PubMed  PubMed Central  Google Scholar 

  • Therrien M, Parker JA (2014) Worming forward: amyotrophic lateral sclerosis toxicity mechanisms and genetic interactions in Caenorhabditis elegans. Front Genet 5:1–13

    CAS  Google Scholar 

  • Thibault O, Gant J, Landfield P (2007) Expansion of the calcium hypothesis of brain aging and Alzheimer’s disease: Minding the store. Aging Cell 6:307–317

    CAS  PubMed  Google Scholar 

  • Tomlinson BE, Blessed G, Roth M (1968) Observations on the brains of non-demented old people. J Neurol Sci 7:331–356

    CAS  PubMed  Google Scholar 

  • Toth ML, Melentijevic I, Shah L et al (2012) Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system. J Neurosci 32:8778–8790

    CAS  PubMed  PubMed Central  Google Scholar 

  • Troulinaki K, Tavernarakis N (2005) Neurodegenerative conditions associated with ageing: a molecular interplay? Mech Ageing Dev 126:23–33

    CAS  PubMed  Google Scholar 

  • Uemura E, Ireland WP (1985) Dendritic alterations in chronic animals with experimental neurofibrillary changes. Exp Neurol 89:530–542

    CAS  PubMed  Google Scholar 

  • Vaughan DW (1977) Age-related deterioration of pyramidal cell basal dendrites in rat auditory cortex. J Comp Neurol 171:501–515

    CAS  PubMed  Google Scholar 

  • Vayndorf EM, Scerbak C, Hunter S, et al (2016) Morphological remodeling of c. Elegans neurons during aging is modified by compromised protein homeostasis. npj Aging Mech Dis 2:

  • Vernooij MW, de Groot M, van der Lugt A et al (2008) White matter atrophy and lesion formation explain the loss of structural integrity of white matter in aging. Neuroimage 43:470–477

    CAS  PubMed  Google Scholar 

  • Vijayan V, Verstreken P (2017) Autophagy in the presynaptic compartment in health and disease. J Cell Biol 216:1895–1906

    CAS  PubMed  PubMed Central  Google Scholar 

  • von Bohlen und Halbach et al (2006) Age-related alterations in hippocampal spines and deficiencies in spatial memory in mice. J Neurosci Res 83:525–531

  • Wentzell J, Kretzschmar D (2010) Alzheimer’s disease and Tauopathy studies in flies and worms. Neurobiol Dis 40:21–28

    CAS  PubMed  PubMed Central  Google Scholar 

  • West MJ, Coleman PD, Flood DG, Troncoso JC (1994) Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer’s disease. Lancet 344:769–772

    CAS  PubMed  Google Scholar 

  • White KE, Humphrey DM, Hirth F (2010) The dopaminergic system in the aging brain of Drosophila. Front Neurosci 4:205

    PubMed  PubMed Central  Google Scholar 

  • Whitfield C, Cziko A, Robinson G (2003) Gene expression profiles in the brain predict behavior in individual honey bees. Science (80- ) 302:296–299

  • Wilson RI (2013) Early olfactory processing in Drosophila: mechanisms and principles. Annu Rev Neurosci 36:217–241

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wisniewski H, Terry RD (1973) Morphology of the aging brain, human and animal. Neurobiol Asp Matur Aging 40:167–186

    CAS  Google Scholar 

  • Withers GS, Fahrbach SE, Robinson GE (1993) Selective neuroanatomical plasticity and division of labour in the honeybee. Nature 364:238–240

    CAS  PubMed  Google Scholar 

  • Wolschin F, Münch D, Amdam GV (2009) Structural and proteomic analyses reveal regional brain differences during honeybee aging. J Exp Biol 212:4027–4032

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yankner BA, Lu T, Loerch P (2008) The aging brain. Annu Rev Pathol 3:41–66

    CAS  PubMed  Google Scholar 

  • Youssef K, Tandon A, Rezai P (2019) Studying Parkinson’s disease using Caenorhabditis elegans models in microfluidic devices. Integr Biol (Camb) 11:186–207

    Google Scholar 

  • Zahn JM, Poosala S, Owen AB et al (2007) AGEMAP: A gene expression database for aging in mice. PLoS Genet 3:2326–2337

    CAS  Google Scholar 

Download references

Funding

NIH Grant NS054814-14 to V.H.

Author information

Authors and Affiliations

  1. Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles (UCLA), Los Angeles, California, USA

    Sandra C. Koch, Annie Nelson & Volker Hartenstein

Authors
  1. Sandra C. Koch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annie Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Volker Hartenstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Volker Hartenstein.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Koch, S.C., Nelson, A. & Hartenstein, V. Structural aspects of the aging invertebrate brain. Cell Tissue Res 383, 931–947 (2021). https://doi.org/10.1007/s00441-020-03314-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-020-03314-6

Keyword

Search

Navigation