High-frequency stimulation (HFS) of the ventrolateral (VL) thalamus is effective in treating the resting tremor of Parkinson's disease (PD). PD is a movement disorder that involves neurodegeneration, predominantly of the substantia nigra, but also in other brain areas, such as the motor cortex and hippocampus. The mechanisms of action of HFS on remote brain areas at the molecular level are largely unknown. Here, we investigated gene expression profiles using oligonucleotide microarrays and quantitative real-time PCR in rat hippocampi. We showed that chronic (14days) HFS modulates the expression of 176 hippocampal genes. Our results showed that genes involved in proliferation and neurogenesis-related biological functions were specifically regulated by HFS, including nestin (Nes) and doublecortin (Dcx), which are expressed in neural progenitor cells and immature neurons, respectively, as well as genes encoding proteins that may support neural differentiation or migration, such as Timp1, Ccl2, S100a4 and Angpt2. Next, we used quantitative real-time PCR (RT-PCR) to profile these six genes in the motor cortex and the caudate-putamen, which included the subventricular zone (CPu-SVZ). Interestingly, HFS increased Dcx expression in the motor cortex whereas Nes was upregulated in the CPu-SVZ but not in the motor cortex. In the CPu-SVZ Timp1 and Ccl2 were highly upregulated by HFS. In conclusion, our findings suggest that HFS may enhance neuroplasticity at the molecular level in several remote brain areas such as the CPu-SVZ, motor cortex and hippocampus.
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