To elucidate the role of the GABAergic neuronal system in the recovery from peripheral vestibular damage (unilateral labyrinthectomy), we used a real-time quantitative reverse transcription-polymerase chain reaction method to investigate the mRNA expression of GAD65, GAD67, the GABAA receptor alpha1 subunit, the GABAB R1 subunit, and the GABA transporter GAT1, in the vestibular nucleus complex of the rat 6 and 50 h following the lesion GAD65 and GAD67 gene expression were also measured in the flocculus. The GABAA alpha 1 subunit mRNA was up-regulated in the ipsilateral vestibular nucleus 6 h post-lesion but decreased in expression thereafter. GAD65 mRNA was up-regulated in the vestibular nuclei bilaterally 50 h after the lesion. In the flocculus, GAD65 mRNA expression was bilaterally up-regulated 50 h post-operatively. GAT1 mRNA expression was initially up-regulated in the ipsilateral vestibular nucleus and then underwent a bilateral increase 50 h post-operatively. These results demonstrate that following unilateral labyrinthectomy, major changes in the expression of GAD, GAT and GABA receptor subunit genes occur in the vestibular nucleus, which are likely to affect the process of behavioural recovery.

Neurogenesis is known to occur in response to injury in the brain, for example, as a result of neurodegenerative diseases. However, there have been few investigations into how the brain responds to damage to peripheral sensory nerves, in other areas such as the brainstem. Here, we report that bilateral surgical lesions of the cochlea result in increased incorporation of the DNA replication marker, bromodeoxyuridine (BrdU), in cells of the brainstem cochlear nucleus (CN) of the adult rat, suggesting either cell proliferation or DNA repair. Some of the BrdU-labelled cells colabelled for the mature neuron marker, NeuN and the GABAergic enzyme GAD-65, suggesting the possibility that neurogenesis might have occurred and resulted in the generation of new neurons with a GABAergic phenotype. However, some of the mature neurons also re-expressed immature neuronal intermediate filament and microtuble-associated proteins, without apoptotic neuronal death, which suggests that the colabelling of BrdU with NeuN and GAD-65 may not be a true reflection of neurogenesis, but injury-stimulated neuronal dedifferentiation. These results suggest the possibility that DNA repair, neuronal de-differentiation or possible neurogenesis occurs in the cochlear nucleus, in response to damage to the peripheral auditory system.

To investigate the molecular background of vestibular compensation, a model of lesion-induced plasticity, we used a microarray analysis to examine genes that show asymmetrical expression between the bilateral vestibular nucleus complexes (VNCs) 6 h following unilateral vestibular deafferentation (UVD). Asymmetrical gene expression was then validated by a real-time quantitative PCR. Among the 88 genes for which the ipsilateral (ipsi) : contralateral (contra) was > 1.35, the number of known genes was 33 (38%), and the number of expressed sequence tag (EST) sequences was 55 (62%). Among the 130 genes for which the contra : ipsi was > 1.35, the number of known genes was 55 (42%), and the number of EST sequences was 75 (58%). Changes in some of the genes were consistent with previous studies; however, we found several new genes which could be functionally related to the molecular basis of the electrophysiological asymmetry between the VNCs following UVD. Ipsi > contra genes included the GABA A receptor rho subunit, regulatory proteins of G protein signaling, calcium signaling related molecules such as the voltage-dependent calcium channel a2/d subunit 1, calcineurin subunit Ab and Ca 2+ pump. Contra > ipsi genes included the neuronal high affinity glutamate transporter, 5-hydroxytryptamine receptor 1D, mitogen-activated protein kinase 12 and ubiquitin carboxy-terminal hydrolase L1.

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