Similar cation channels mediate protection from cerebellar exitotoxicity by exercise and inheritance.
Bottom Line: Sedentary FVB/N and exercised C57BL/6 mice both expressed higher levels of these cation channels compared to sedentary C57BL/6 mice, and were both found to be less sensitive to glutamate toxicity.In addition, our findings highlight the involvement of the cholinergic anti-inflammatory pathway in insult-inducible cerebellar processes.These mechanisms are likely to play similar roles in other brain regions and injuries as well, opening new venues for targeted research efforts.
Affiliation: Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.Show MeSH
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Mentions: We surmised that in addition to BG, other neighbouring structures protect PCs from glutamate excito-toxicity. Specifically, we suspected the pinceau region of BCs. To challenge this prediction, we examined the expression levels of four voltage-dependent channels that are highly prevalent in the pinceau, namely HCN1, KVβ2, KV1.2 and the γ-amino butyric acid (GABA) transporter—GAT1A. The cerebellar pinceau of exercised C57BL/6 and sedentary FVB/N mice, both relatively resistant to kainate, showed higher levels than sedentary C57BL/6 mice of both HCN1 (n ∇ 6 per group, P < 0.0005 and 0.0083, respectively, Fig. 4A) and KVβ2 (n ∇ 6 per group, P < 0.0005 and 0.00045, respectively, Fig. 4B). Interestingly, HCN1 but not KVβ2 staining could also be seen outside the pinceau (Fig. 4A, white arrows). Thus, resistance to glutamate toxicity correlated with elevated expression levels of both HCN1 and KVβ2 in the pinceau and of Kir6.1 in BG.
Affiliation: Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.