GABA(A) receptor agonist and antagonist alter vestibular compensation and different steps of reactive neurogenesis in deafferented vestibular nuclei of adult cats.
Strong reactive cell proliferation occurs in the vestibular nuclei after unilateral vestibular neurectomy (UVN). Most of the newborn cells survive, differentiate into glial cells and neurons with GABAergic phenotype, and have been reported to contribute to recovery of the posturo-locomotor functions in adult cats. Because the GABAergic system modulates vestibular function recovery and the different steps of neurogenesis in mammals, we aimed to examine in our UVN animal model the effect of chronic infusion of GABA(A) receptor (R) agonist and antagonist in the vestibular nuclei. After UVN and one-month intracerebroventricular infusions of saline, GABA(A)R agonist (muscimol) or antagonist (gabazine), cell proliferation and differentiation into astrocytes, microglial cells, and neurons were revealed using immunohistochemical methods. We also determined the effects of these drug infusions on the recovery of posturo-locomotor and oculomotor functions through behavioral tests. Our results showed that surprisingly, one month after UVN, newborn cells did not survive in the UVN-muscimol group whereas the number of GABAergic pre-existent neurons increased, and the long-term behavioral recovery of the animals was drastically impaired. Conversely, a significant number of newborn cells survived up to 1 month in the UVN-gabazine group whereas the astroglial population increased, and these animals showed the fastest recovery in behavioral functions. This study reports for the first time that GABA plays multiple roles, ranging from beneficial to detrimental on the different steps of a functional postlesion neurogenesis and further, strongly influences the time course of vestibular function recovery.
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06519, and Laboratoire de Neurosciences Intégratives et Adaptatives, UMR 7260 Aix-Marseille Université-CNRS, Fédération de Recherche 3C, 13331 Marseille Cedex 03, France.
Sophie
S
Dutheil
Guy
G
Escoffier
Ali
A
Gharbi
Isabelle
I
Watabe
Brahim
B
Tighilet
D000818:Animals; D001253:Astrocytes / Q000166:cytology; D002415:Cats; D049109:Cell Proliferation; D003714:Denervation; D005133:Eye Movements; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D059330:GABAergic Neurons / Q000166:cytology* / Q000187:drug effects; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D055495:Neurogenesis; D004856:Postural Balance; D011724:Pyridazines / Q000494:pharmacology*; D014725:Vestibular Nerve / Q000601:surgery; D014726:Vestibular Nuclei / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
D018755:GABA Agonists; D018756:GABA Antagonists; D011724:Pyridazines; D009118:Muscimol; C049853:gabazine