Asymmetric gene expression in the brain during acute compensation to unilateral vestibular labyrinthectomy in the Mongolian gerbil

Commercial microarrays were used to identify transcriptome expression within vestibular related brain regions (vestibular brainstem and cerebellum, and caudotemporal cortical regions) during the acute period of recovery following unilateral surgical vestibular labyrinth ablation in the gerbil. As a representative model of vestibular compensation, vestibular lesions in the gerbil produced activation in a common set of genes related to vestibular compensation. The total RNA was prepared and amplified using Affymetrix Gene Chip™ probes from the Rat U34 Neurobiology and R230, and Mouse M430 gene sets, resulting in GCRMA summarized data from S+AA software. Matched rat and mouse genes from gerbil hybridization produced good interspecies synteny. Multiple gene target trends supported global increases in neuron excitability throughout the vestibular brainstem and cerebellum. We focused further on gene expression with anatomically asymmetric activation relative to the lesion, indicative of involvement in rebalancing central vestibular tone during the vestibular compensation process. Cluster analysis revealed distinct spatial (regional and ipsi-contra) and temporal patterns. The asymmetric genes were part of well-defined neuron-related networks and included multiple members of the glutamate and GABA neurotransmitter systems. Transcripts for D3 dopamine, glycine, and some GABA receptor signals increased quickly in the ipsilesional vestibular complex and then increased gradually in the contralateral region, restoring the expression symmetry. Alternatively, the NMDA binding subunit decreased gradually over the acute compensation period in the contralateral vestibular complex. There was evidence for numerous associations between signaling systems with PKC as one possible mediator between early changes in GABA and progressive changes in NMDA signaling. These data begin to define the compensatory response at the level of molecular cascades.