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Age-related loss of VGLUT1 excitatory, but not VGAT inhibitory, immunoreactive terminals on motor neurons in spinal cords of old sarcopenic male mice

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Abstract

Age-related changes in ventral lumbar spinal cord (L3–L5) were compared in young [3 month, (M)] and old (27 M) C57BL/6J male mice. The aged mice had previously been shown to exhibit sarcopenia and changes to peripheral nerve morphology. The putative connectivity of β-III tubulin positive α-motor neurons was compared in immunostained transverse sections using excitatory and inhibitory terminal markers vesicular glutamate transporter-1 (VGLUT1) and vesicular GABA transporter (VGAT). Glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) immunostaining was used to monitor changes in astrocyte and microglial phenotype respectively. For a given motor neuron, the neuronal perimeter was outlined and terminals immunoreactive for VGLUT1 or VGAT in close apposition to the soma were identified. By 27 M, the percentage coverage and total number of VGLUT1 immunoreactive terminals immediately adjacent to the soma of α-motor neurons was significantly decreased compared with young mice. However, percentage coverage of immunoreactive VGAT inhibitory terminals did not change significantly with age. The gray matter of 27 M spinal cords showed increased astrocytic and microglial activity. The loss of VGLUT1 terminals on α-motor neurons, terminals known to be derived from proprioceptive muscle afferents, may further impair sensorimotor control of hind limb skeletal muscle function in old mice.

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References

  • Aagaard P, Suetta C, Caserotti P, Magnusson SP, Kjaer M (2010) Role of the nervous system in sarcopenia and muscle atrophy with aging: strength training as a countermeasure. Scand J Med Sci Sports 20:49–64

    Article  PubMed  CAS  Google Scholar 

  • Akay T, Tourtellotte WG, Arber S, Jessell TM (2014) Degradation of mouse locomotor pattern in the absence of proprioceptive sensory feedback. Proc Natl Acad Sci 111:16877–16882

    Article  PubMed  CAS  Google Scholar 

  • Alvarez FJ, Villalba RM, Zerda R, Schneider SP (2004) Vesicular glutamate transporters in the spinal cord, with special reference to sensory primary afferent synapses. J Comp Neurol 472:257–280

    Article  PubMed  CAS  Google Scholar 

  • Alvarez FJ, Titus-Mitchell HE, Bullinger KL, Kraszpulski M, Nardelli P, Cope TC (2011) Permanent central synaptic disconnection of proprioceptors after nerve injury and regeneration. I. Loss of VGLUT1/IA synapses on motoneurons. J Neurophysiol 106:2450–2470

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bala U, Tan KL, Ling KH, Cheah PS (2014) Harvesting the maximum length of sciatic nerve from adult mice: a step-by-step approach. BMC Res Notes 7:714

    Article  PubMed  PubMed Central  Google Scholar 

  • Balschun D, Moechars D, Callaerts-Vegh Z, Vermaercke B, Van Acker N, Andries L, D’Hooge R (2010) Vesicular glutamate transporter VGLUT1 has a role in hippocampal long-term potentiation and spatial reversal learning. Cereb Cortex 20:684–693

    Article  PubMed  Google Scholar 

  • Banuelos C, Beas BS, McQuail JA, Gilbert RJ, Frazier CJ, Setlow B, Bizon JL (2014) Prefrontal cortical GABAergic dysfunction contributes to age-related working memory impairment. J Neurosci 34:3457–3466

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Barbeito LH et al (2004) A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis. Brain Res Brain Res Rev 47:263–274

    Article  PubMed  CAS  Google Scholar 

  • Barrett CP, Guth L, Donati EJ, Krikorian JG (1981) Astroglial reaction in the gray matter lumbar segments after midthoracic transection of the adult rat spinal cord. Exp Neurol 73:365–377

    Article  PubMed  CAS  Google Scholar 

  • Bernardinelli Y, Muller D, Nikonenko I (2014) Astrocyte-synapse structural plasticity. Neural Plast 2014:232105

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brettschneider J, Toledo JB, Van Deerlin VM, Elman L, McCluskey L, Lee VM, Trojanowski JQ (2012) Microglial activation correlates with disease progression and upper motor neuron clinical symptoms in amyotrophic lateral sclerosis. PLoS ONE 7:e39216

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brumovsky PR (2013) VGLUTs in peripheral neurons and the spinal cord: time for a review. ISRN Neurol 2013:829753

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Brumovsky P, Watanabe M, Hokfelt T (2007) Expression of the vesicular glutamate transporters-1 and -2 in adult mouse dorsal root ganglia and spinal cord and their regulation by nerve injury. Neuroscience 147:469–490

    Article  PubMed  CAS  Google Scholar 

  • Canas PM, Duarte JM, Rodrigues RJ, Kofalvi A, Cunha RA (2009) Modification upon aging of the density of presynaptic modulation systems in the hippocampus. Neurobiol Aging 30:1877–1884

    Article  PubMed  CAS  Google Scholar 

  • Casale EJ, Light AR, Rustioni A (1988) Direct projection of the corticospinal tract to the superficial laminae of the spinal cord in the rat. J Comp Neurol 278:275–286

    Article  PubMed  CAS  Google Scholar 

  • Chai RJ, Vukovic J, Dunlop S, Grounds MD, Shavlakadze T (2011) Striking denervation of neuromuscular junctions without lumbar motoneuron loss in geriatric mouse muscle. PLoS ONE 6:1–11

    Google Scholar 

  • Clark AK, Gruber-Schoffnegger D, Drdla-Schutting R, Gerhold KJ, Malcangio M, Sandkuhler J (2015) Selective activation of microglia facilitates synaptic strength. J Neurosci 35:4552–4570

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • D’Acunzo P, Badaloni A, Ferro M, Ripamonti M, Zimarino V, Malgaroli A, Consalez GG (2014) A conditional transgenic reporter of presynaptic terminals reveals novel features of the mouse corticospinal tract. Front Neuroanat 7:50

    Article  PubMed  PubMed Central  Google Scholar 

  • Damoiseaux JG, Dopp EA, Calame W, Chao D, MacPherson GG, Dijkstra CD (1994) Rat macrophage lysosomal membrane antigen recognized by monoclonal antibody ED1. Immunology 83:140–147

    PubMed  PubMed Central  CAS  Google Scholar 

  • Deak F, Sonntag WE (2012) Aging, synaptic dysfunction, and insulin-like growth factor (IGF)-1. J Gerontol 67:611–625

    Article  CAS  Google Scholar 

  • Doherty TJ (2003) Invited review: aging and sarcopenia. J Appl Physiol 95:1717–1727

    Article  PubMed  CAS  Google Scholar 

  • Drey M, Krieger B, Sieber CC, Bauer JM, Hettwer S, Bertsch T, DISARCO Study Group (2014) Motoneuron loss is associated with sarcopenia. J Am Med Dir Assoc 15:435–439

    Article  PubMed  Google Scholar 

  • Duan W, Zhang R, Guo Y, Jiang Y, Huang Y, Jiang H, Li C (2009) Nrf2 activity is lost in the spinal cord and its astrocytes of aged mice. In Vitro Cell Dev Biol Anim 45:388–397

    Article  PubMed  CAS  Google Scholar 

  • Edstrom E, Altun M, Bergman E, Johnson H, Kullberg S, Ramirez-Leon V, Ulfhake B (2007) Factors contributing to neuromuscular impairment and sarcopenia during aging. Physiol Behav 92:129–135

    Article  PubMed  CAS  Google Scholar 

  • Fremeau RT Jr et al (2004) Vesicular glutamate transporters 1 and 2 target to functionally distinct synaptic release sites. Science 304:1815–1819

    Article  PubMed  CAS  Google Scholar 

  • Friese A, Kaltschmidt JA, Ladle DR, Sigrist M, Jessell TM, Arber S (2009) Gamma and alpha motor neurons distinguished by expression of transcription factor Err3. Proc Natl Acad Sci 106:13588–13593

    Article  PubMed  Google Scholar 

  • Hashizume K, Kanda K (1995) Differential effects of aging on motoneurons and peripheral nerves innervating the hindlimb and forelimb muscles of rats. Neurosci Res 22:189–196

    Article  PubMed  CAS  Google Scholar 

  • Hodgetts SI, Simmons PJ, Plant GW (2013) A comparison of the behavioral and anatomical outcomes in sub-acute and chronic spinal cord injury models following treatment with human mesenchymal precursor cell transplantation and recombinant decorin. Exp Neurol 248:343–359

    Article  PubMed  CAS  Google Scholar 

  • Hu D, Serrano F, Oury TD, Klann E (2006) Aging-dependent alterations in synaptic plasticity and memory in mice that overexpress extracellular superoxide dismutase. J Neurosci 26:3933–3941

    Article  PubMed  CAS  Google Scholar 

  • Jacob JM (1998) Lumbar motor neuron size and number is affected by age in male F344 rats. Mech Ageing Dev 106:205–216

    Article  PubMed  CAS  Google Scholar 

  • Jouhilahti EM, Peltonen S, Peltonen J (2008) Class III beta-tubulin is a component of the mitotic spindle in multiple cell types. J Histochem Cytochem 56:1113–1119

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kane CJ, Sims TJ, Gilmore SA (1997) Astrocytes in the aged rat spinal cord fail to increase GFAP mRNA following sciatic nerve axotomy. Brain Res 759:163–165

    Article  PubMed  CAS  Google Scholar 

  • Kanning KC, Kaplan A, Henderson CE (2010) Motor neuron diversity in development and disease. Annu Rev Neurosci 33:409–440

    Article  PubMed  CAS  Google Scholar 

  • Karimi-Abdolrezaee S, Billakanti R (2012) Reactive astrogliosis after spinal cord injury-beneficial and detrimental effects. Mol Neurobiol 46:251–264

    Article  PubMed  CAS  Google Scholar 

  • Kawamura Y, O’Brien P, Okazaki H, Dyck PJ (1977) Lumbar motoneurons of man II: the number and diameter distribution of large- and intermediate-diameter cytons in “motoneuron columns” of spinal cord of man. J Neuropathol Exp Neurol 36:861–870

    Article  PubMed  CAS  Google Scholar 

  • Kirkpatrick LJ, Yablonka-Reuveni Z, Rosser BW (2010) Retention of Pax3 expression in satellite cells of muscle spindles. J Histochem Cytochem 58:317–327

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Krishnan VS et al (2016) A neurogenic perspective of sarcopenia: time course study of sciatic nerves from aging mice. J Neuropathol Exp Neurol 75:464–478

    Article  PubMed  CAS  Google Scholar 

  • Kullberg S, Ramirez-Leon V, Johnson H, Ulfhake B (1998) Decreased axosomatic input to motoneurons and astrogliosis in the spinal cord of aged rats. J Gerontol 53:B369–B379

    Article  CAS  Google Scholar 

  • Kullberg S, Aldskogius H, Ulfhake B (2001) Microglial activation, emergence of ED1-expressing cells and clusterin upregulation in the aging rat CNS, with special reference to the spinal cord. Brain Res 899:169–186

    Article  PubMed  CAS  Google Scholar 

  • Kwan P (2013) Sarcopenia: the gliogenic perspective. Mech Ageing Dev 134:349–355

    Article  PubMed  CAS  Google Scholar 

  • Lee S, Wu Y, Shi XQ, Zhang J (2015) Characteristics of spinal microglia in aged and obese mice: potential contributions to impaired sensory behavior. Immun Ageing 12:22

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Levine AJ, Hinckley CA, Hilde KL, Driscoll SP, Poon TH, Montgomery JM, Pfaff SL (2014) Identification of a cellular node for motor control pathways. Nat Neurosci 17:586–593

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lexell J (1997) Evidence for nervous system degeneration with advancing age. J Nutr 127:1011S–1013S

    Article  PubMed  CAS  Google Scholar 

  • Li JL, Fujiyama F, Kaneko T, Mizuno N (2003) Expression of vesicular glutamate transporters, VGluT1 and VGluT2, in axon terminals of nociceptive primary afferent fibers in the superficial layers of the medullary and spinal dorsal horns of the rat. J Comp Neurol 457:236–249

    Article  PubMed  CAS  Google Scholar 

  • Liguz-Lecznar M, Lehner M, Kaliszewska A, Zakrzewska R, Sobolewska A, Kossut M (2015) Altered glutamate/GABA equilibrium in aged mice cortex influences cortical plasticity. Brain Struct Funct 220:1681–1693

    Article  PubMed  CAS  Google Scholar 

  • Ling KK, Lin MY, Zingg B, Feng Z, Ko CP (2010) Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy. PLoS ONE 5:e15457

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu C, Ward PJ, English AW (2014) The effects of exercise on synaptic stripping require androgen receptor signaling. PLoS ONE 9:e98633

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lord SR, Ward JA (1994) Age-associated differences in sensori-motor function and balance in community dwelling women. Age Ageing 23:452–460

    Article  PubMed  CAS  Google Scholar 

  • Lynch AM et al (2010) The impact of glial activation in the aging brain. Aging Dis 1:262–278

    PubMed  PubMed Central  Google Scholar 

  • Maeda H et al (2016) Corticospinal axons make direct synaptic connections with spinal motoneurons innervating forearm muscles early during postnatal development in the rat. J Physiol 594:189–205

    Article  PubMed  CAS  Google Scholar 

  • Martin JE et al (2017) Decreased motor neuron support by SMA astrocytes due to diminished MCP1 secretion. J Neurosci 37:5309–5318

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Maxwell N et al (2018) alpha-Motor neurons are spared from aging while their synaptic inputs degenerate in monkeys and mice. Aging Cell. https://doi.org/10.1111/acel.12726

    Article  PubMed  PubMed Central  Google Scholar 

  • McIntire SL, Reimer RJ, Schuske K, Edwards RH, Jorgensen EM (1997) Identification and characterization of the vesicular GABA transporter. Nature 389:870–876

    Article  PubMed  CAS  Google Scholar 

  • Mentis GZ et al (2011) Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy. Neuron 69:453–467

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Misawa H, Hara M, Tanabe S, Niikura M, Moriwaki Y, Okuda T (2012) Osteopontin is an alpha motor neuron marker in the mouse spinal cord. J Neurosci Res 90:732–742

    Article  PubMed  CAS  Google Scholar 

  • Mittal KR, Logmani FH (1987) Age-related reduction in 8th cervical ventral nerve root myelinated fiber diameters and numbers in man. J Gerontol 42:8–10

    Article  PubMed  CAS  Google Scholar 

  • Monti B, Virgili M, Contestabile A (2004) Alterations of markers related to synaptic function in aging rat brain, in normal conditions or under conditions of long-term dietary manipulation. Neurochem Int 44:579–584

    Article  PubMed  CAS  Google Scholar 

  • Morisaki Y et al (2016) Selective expression of osteopontin in ALS-resistant motor neurons is a critical determinant of late phase neurodegeneration mediated by matrix metalloproteinase-9. Sci Rep 6:27354

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Nakajima K, Kohsaka S (2001) Microglia: activation and their significance in the central nervous system. J Biochem 130:169–175

    Article  PubMed  CAS  Google Scholar 

  • Norden DM, Godbout JP (2013) Review: microglia of the aged brain: primed to be activated and resistant to regulation. Neuropathol Appl Neurobiol 39:19–34

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Oliveira AL et al (2003) Cellular localization of three vesicular glutamate transporter mRNAs and proteins in rat spinal cord and dorsal root ganglia. Synapse 50:117–129

    Article  PubMed  CAS  Google Scholar 

  • Owens DF, Kriegstein AR (2002) Is there more to GABA than synaptic inhibition? Nat Rev Neurosci 3:715–727

    Article  PubMed  CAS  Google Scholar 

  • Pannerec A et al (2016) A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia. Aging 8:712–729

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Persson S et al (2006) Distribution of vesicular glutamate transporters 1 and 2 in the rat spinal cord, with a note on the spinocervical tract. J Comp Neurol 497:683–701

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Proske U, Wise AK, Gregory JE (2000) The role of muscle receptors in the detection of movements. Progress Neurobiol 60:85–96

    Article  CAS  Google Scholar 

  • Purves D (2001) Neuroscience. The motor unit, 2nd edn. Sinauer Associates, Sunderland

    Google Scholar 

  • Ranson RN, Santer RM, Watson AH (2007) Ageing reduces the number of vesicular glutamate transporter 2 containing immunoreactive inputs to identified rat pelvic motoneurons. Exp Gerontol 42:506–516

    Article  PubMed  CAS  Google Scholar 

  • Ribeiro F, Oliveira J (2007) Aging effects on joint proprioception: the role of physical activity in proprioception preservation. Eur Rev Aging Phys Act 4:71–76

    Article  Google Scholar 

  • Ridet JL, Malhotra SK, Privat A, Gage FH (1997) Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci 20:570–577

    Article  PubMed  CAS  Google Scholar 

  • Rigaud M, Gemes G, Barabas ME, Chernoff DI, Abram SE, Stucky CL, Hogan QH (2008) Species and strain differences in rodent sciatic nerve anatomy: implications for studies of neuropathic pain. Pain 136:188–201

    Article  PubMed  PubMed Central  Google Scholar 

  • Ritzel RM, Patel AR, Pan S, Crapser J, Hammond M, Jellison E, McCullough LD (2015) Age- and location-related changes in microglial function. Neurobiol Aging 36:2153–2163

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Arellano JJ, Parpura V, Zorec R, Verkhratsky A (2016) Astrocytes in physiological aging and Alzheimer’s disease. Neuroscience 323:170–182

    Article  PubMed  CAS  Google Scholar 

  • Rotterman TM, Nardelli P, Cope TC, Alvarez FJ (2014) Normal distribution of VGLUT1 synapses on spinal motoneuron dendrites and their reorganization after nerve injury. J Neurosci 34:3475–3492

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rozycka A, Liguz-Lecznar M (2017) The space where aging acts: focus on the GABAergic synapse. Aging Cell 16:634–643

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sasaki Y, Ohsawa K, Kanazawa H, Kohsaka S, Imai Y (2001) Iba1 is an actin-cross-linking protein in macrophages/microglia. Biochem Biophys Res Commun 286:292–297

    Article  PubMed  CAS  Google Scholar 

  • Schmidt S, Redecker C, Bruehl C, Witte OW (2010) Age-related decline of functional inhibition in rat cortex. Neurobiol Aging 31:504–511

    Article  PubMed  CAS  Google Scholar 

  • Siskova Z, Tremblay ME (2013) Microglia and synapse: interactions in health and neurodegeneration. Neural Plast 2013:425845

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Soffe Z, Radley-Crabb HG, McMahon C, Grounds MD, Shavlakadze T (2016) Effects of loaded voluntary wheel exercise on performance and muscle hypertrophy in young and old male C57BL/6J mice. Scand J Med Sci Sports 26:172–188

    Article  PubMed  CAS  Google Scholar 

  • Sorensen KL, Hollands MA, Patla E (2002) The effects of human ankle muscle vibration on posture and balance during adaptive locomotion. Exp Brain Res 43:24–34

    Article  Google Scholar 

  • Stanley EM, Fadel JR, Mott DD (2012) Interneuron loss reduces dendritic inhibition and GABA release in hippocampus of aged rats. Neurobiol Aging 33:431-e1

    Article  CAS  Google Scholar 

  • Suetterlin KJ, Sayer AA (2014) Proprioception: where are we now? A commentary on clinical assessment, changes across the life course, functional implications and future interventions. Age Ageing 43:313–318

    Article  PubMed  Google Scholar 

  • Sunagawa M et al (2017) Distinct development of the glycinergic terminals in the ventral and dorsal horns of the mouse cervical spinal cord. Neuroscience 343:459–471

    Article  PubMed  CAS  Google Scholar 

  • Sutherland TC, Mathews KJ, Mao Y, Nguyen T, Gorrie CA (2016) Differences in the cellular response to acute spinal cord injury between developing and mature rats highlights the potential significance of the inflammatory response. Front Cell Neurosci 10:310

    PubMed  Google Scholar 

  • Sykova E, Mazel T, Hasenohrl RU, Harvey AR, Simonova Z, Mulders WH, Huston JP (2002) Learning deficits in aged rats related to decrease in extracellular volume and loss of diffusion anisotropy in hippocampus. Hippocampus 12:269–279

    Article  PubMed  CAS  Google Scholar 

  • Taves S, Berta T, Chen G, Ji RR (2013) Microglia and spinal cord synaptic plasticity in persistent pain. Neural Plast 2013:753656

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Thornell LE, Carlsson L, Eriksson PO, Liu JX, Osterlund C, Stal P, Pedrosa-Domellof F (2015) Fibre typing of intrafusal fibres. J Anat 227:136–156

    Article  PubMed  PubMed Central  Google Scholar 

  • Todd AJ, Hughes DI, Polgar E, Nagy GG, Mackie M, Ottersen OP, Maxwell DJ (2003) The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal horn. Eur J Neurosci 17:13–27

    Article  PubMed  CAS  Google Scholar 

  • Tomlinson BE, Irving D (1977) The numbers of limb motor neurons in the human lumbosacral cord throughout life. J Neurol Sci 34:213–219

    Article  PubMed  CAS  Google Scholar 

  • Triolo D et al (2006) Loss of glial fibrillary acidic protein (GFAP) impairs Schwann cell proliferation and delays nerve regeneration after damage. J Cell Sci 119:3981–3993

    Article  PubMed  CAS  Google Scholar 

  • Valdez G, Tapia JC, Kang H, Clemenson GD Jr, Gage FH, Lichtman JW, Sanes JR (2010) Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise. Proc Natl Acad Sci 107:14863–14868

    Article  PubMed  Google Scholar 

  • van der Poel C, Gosselin LE, Schertzer JD, Ryall JG, Swiderski K, Wondemaghen M, Lynch GS (2011) Ageing prolongs inflammatory marker expression in regenerating rat skeletal muscles after injury. J Inflamm (Lond) 8:41

    Article  PubMed Central  CAS  Google Scholar 

  • VanGuilder HD, Yan H, Farley JA, Sonntag WE, Freeman WM (2010) Aging alters the expression of neurotransmission-regulating proteins in the hippocampal synaptoproteome. J Neurochem 113:1577–1588

    PubMed  PubMed Central  CAS  Google Scholar 

  • Vaughan SK, Stanley OL, Valdez G (2017) Impact of aging on proprioceptive sensory neurons and intrafusal muscle fibers in mice. J Gerontol 72:771–779

    Google Scholar 

  • Watson C, Paxinos G, Kayalioglu G, Kayalioglu G, Christopher & Dana Reeve Foundation (2009) The spinal cord: a Christopher and Dana Reeve Foundation text and atlas, 1st edn. Elsevier/Academic Press, London

    Google Scholar 

  • Welniarz Q, Dusart I, Roze E (2017) The corticospinal tract: evolution, development, and human disorders. Dev Neurobiol 77:810–829

    Article  PubMed  Google Scholar 

  • White Z, White RB, McMahon C, Grounds MD, Shavlakadze T (2016) High mTORC1 signaling is maintained, while protein degradation pathways are perturbed in old murine skeletal muscles in the fasted state. Int J Biochem Cell Biol 78:10–21

    Article  PubMed  CAS  Google Scholar 

  • Wojcik SM et al (2004) An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size. Proc Natl Acad Sci 101:7158–7163

    Article  PubMed  CAS  Google Scholar 

  • You SW et al (2016) Large-scale reconstitution of a retina-to-brain pathway in adult rats using gene therapy and bridging grafts: an anatomical and behavioral analysis. Exp Neurol 279:197–211

    Article  PubMed  CAS  Google Scholar 

  • Zhu X, Ward PJ, English AW (2016) Selective requirement for maintenance of synaptic contacts onto motoneurons by target-derived trkB receptors. Neural Plast 2016:2371893

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

This research was made possible by funding from a Central grant from the University of Western Australia (UWA, for MG), the WA Neurotrauma Research Programme (for MG, ARH, SH and VSK), and an International Postgraduate Scholarship and a Postgraduate Scholarship for International Tuition Fees from UWA (for VSK). We thank Professor Charles Watson for helpful discussions.

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  1. School of Human Sciences, The University of Western Australia, Perth, WA, 6009, Australia

    Vidya S. Krishnan, Tea Shavlakadze, Miranda D. Grounds, Stuart I. Hodgetts & Alan R. Harvey

  2. Perron Institute for Neurological and Translational Science, Nedlands, WA, 6009, Australia

    Stuart I. Hodgetts & Alan R. Harvey

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  1. Vidya S. Krishnan
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  2. Tea Shavlakadze
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Correspondence to Alan R. Harvey.

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Krishnan, V.S., Shavlakadze, T., Grounds, M.D. et al. Age-related loss of VGLUT1 excitatory, but not VGAT inhibitory, immunoreactive terminals on motor neurons in spinal cords of old sarcopenic male mice. Biogerontology 19, 385–399 (2018). https://doi.org/10.1007/s10522-018-9765-5

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