Age-related loss of VGLUT1 excitatory, but not VGAT inhibitory, immunoreactive terminals on motor neurons in spinal cords of old sarcopenic male mice
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.
KeywordsVGLUT1 VGAT Astrocytes Microglia Synaptic transmission Proprioception Sarcopenia
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.
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest.
- 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 6:1–11Google 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 457:236–249CrossRefPubMedGoogle Scholar
- Purves D (2001) Neuroscience. The motor unit, 2nd edn. Sinauer Associates, SunderlandGoogle 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 17:13–27CrossRefPubMedGoogle Scholar
- Vaughan SK, Stanley OL, Valdez G (2017) Impact of aging on proprioceptive sensory neurons and intrafusal muscle fibers in mice. J Gerontol 72:771–779Google 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, LondonGoogle Scholar