Neurogenesis and astrogenesis contribution to recovery of vestibular functions in the adult cat following unilateral vestibular neurectomy: cellular and behavioral evidence.
In physiological conditions, neurogenesis occurs in restricted regions of the adult mammalian brain, giving rise to integrated neurons into functional networks. In pathological or postlesional conditions neurogenesis and astrogenesis can also occur, as demonstrated in the deafferented vestibular nuclei after immediate unilateral vestibular neurectomy (UVN) in the adult cat. To determine whether the reactive cell proliferation and beyond neurogenesis and astrogenesis following UVN plays a functional role in the vestibular functions recovery, we examined the effects of an antimitotic drug: the cytosine-beta-d arabinofuranoside (AraC), infused in the fourth ventricle after UVN. Plasticity mechanisms were evidenced at the immunohistochemical level with bromodeoxyuridine, GAD67 and glial fibrillary acidic protein (GFAP) stainings. Consequences of immediate or delayed AraC infusion on the behavioral recovery processes were evaluated with oculomotor and posturo-locomotor tests. We reported that after UVN, immediate AraC infusion blocked the cell proliferation and decreased the number of GFAP-immunoreactive cells and GABAergic neurons observed in the vestibular nuclei of neurectomized cats. At the behavioral level, after UVN and immediate AraC infusion the time course of posturo-locomotor function recovery was drastically delayed, and no alteration of the horizontal spontaneous nystagmus was observed. In contrast, an infusion of AraC beginning 3 weeks after UVN had no influence neither on the time course of the behavioral recovery, nor on the reactive cell proliferation and its differentiation. We conclude that the first 3 weeks after UVN represent a possible critical period in which important neuroplasticity mechanisms take place for promoting vestibular function recovery: reactive neurogenesis and astrogenesis might contribute highly to vestibular compensation in the adult cat.
UMR 6149 Neurosciences Intégratives et Adaptatives, Pôle 3C, Comportement, Cerveau, Cognition, Centre de St Charles, Case B-3 Place Victor Hugo, 13331 Marseille Cedex 3-France.
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S
Dutheil
J M
JM
Brezun
J
J
Leonard
M
M
Lacour
B
B
Tighilet
D000818:Animals; D050256:Antimitotic Agents / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002415:Cats; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007150:Immunohistochemistry; D008124:Locomotion / Q000187:drug effects; D055495:Neurogenesis; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009759:Nystagmus, Pathologic / Q000503:physiopathology; D011187:Posture; D014722:Vestibule, Labyrinth / Q000166:cytology* / Q000294:innervation*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D050256:Antimitotic Agents; D005904:Glial Fibrillary Acidic Protein; D003561:Cytarabine; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; D001973:Bromodeoxyuridine