title: Peripheral axotomy induces depletion of the vesicular glutamate transporter VGLUT1 in central terminals of myelinated afferent fibres in the rat spinal cord.
abstract: Myelinated primary afferent axons use glutamate as their principal neurotransmitter. We have shown previously that central terminals of myelinated tactile and proprioceptive afferents contain the vesicular glutamate transporter VGLUT1. Peripheral nerve injury is known to induce changes in the anatomy, neurochemistry, and physiology of primary afferents. In this study, we have examined the effect of peripheral axotomy on VGLUT1 expression in central terminals of myelinated afferents in laminae III-V and lamina IX of the rat spinal cord. Bilateral injections of cholera toxin B subunit (CTb) were made into the sciatic nerves of rats that had undergone unilateral sciatic nerve transection 1, 2, 4, or 8 weeks previously. Immunofluorescence staining and confocal microscopy were used to compare levels of VGLUT1 in CTb-labelled boutons on the intact and sectioned sides at each postoperative survival time. VGLUT1 was depleted from central terminals of transected myelinated afferents in rats injected with CTb 1 week after nerve section, and this depletion became more severe in animals with longer postaxotomy survival times. By 4 weeks, the level of VGLUT1 in CTb-labelled boutons in lamina IX was reduced by over 80% compared to that seen in intact (contralateral) afferents, while for boutons in laminae III-V, VGLUT1 levels were reduced by 50-70%. This suggests that loss of VGLUT1 is more severe in proprioceptive than cutaneous afferents. Depletion of VGLUT1 may lead to a decrease in levels of transmitter glutamate in these afferents and thus to a reduction in synaptic efficacy.
authors.affiliation: Spinal Cord Group, Institute of Biomedical and Life Sciences, University of Glasgow, West Medical Building, Glasgow G12 8QQ, UK. d.hughes@bio.gla.ac.uk
authors.forename: David I
authors.initials: DI
authors.lastname: Hughes
authors.forename: Erika
authors.initials: E
authors.lastname: Polgár
authors.forename: Safa A S
authors.initials: SA
authors.lastname: Shehab
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Todd
mesh_terms: D000344:Afferent Pathways / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D019771:Axotomy / Q000009:adverse effects* / Q000379:methods; D002352:Carrier Proteins / Q000378:metabolism*; D002772:Cholera Toxin / Q000493:pharmacokinetics; D005260:Female; D007839:Functional Laterality; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D026901:Membrane Transport Proteins; D009413:Nerve Fibers, Myelinated / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D013997:Time Factors; D050598:Vesicular Glutamate Transport Protein 1; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C493466:Slc17a7 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; D033921:Vesicular Transport Proteins; D002772:Cholera Toxin