Limits...
Similar cation channels mediate protection from cerebellar exitotoxicity by exercise and inheritance.

Ben-Ari S, Ofek K, Barbash S, Meiri H, Kovalev E, Greenberg DS, Soreq H, Shoham S - J. Cell. Mol. Med. (2012)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.

Show MeSH

Related in: MedlinePlus

Higher HCN1 and KVβ2 levels in the cerebellar pinceau of protected mice. Labelling of HCN1 (A) and KVβ2 (B) in the cerebellar pinceau of kainate-injected and exercised C57BL/6 and sedentary FVB/N mice, which show higher resistance to glutamatergic toxicity (green ∇ HCN1 or KVβ2, red ∇ calbindin-28K, n ∇ 6 for each group, insets show the pinceau region). Semi-quantification is based on percentage of HCN1 and KVβ2 immunoreactive stained areas. Control values were 0.04% and 0.4%, respectively. (*P < 0.0005 in comparison to sedentary C57BL/6 mice, post-hoc analysis after one-way ANOVA, #P < 0.005 in comparison to sedentary C57BL/6 mice, Student’s t-test. Arrows indicate staining outside the pinceau).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3822931&req=5

fig04: Higher HCN1 and KVβ2 levels in the cerebellar pinceau of protected mice. Labelling of HCN1 (A) and KVβ2 (B) in the cerebellar pinceau of kainate-injected and exercised C57BL/6 and sedentary FVB/N mice, which show higher resistance to glutamatergic toxicity (green ∇ HCN1 or KVβ2, red ∇ calbindin-28K, n ∇ 6 for each group, insets show the pinceau region). Semi-quantification is based on percentage of HCN1 and KVβ2 immunoreactive stained areas. Control values were 0.04% and 0.4%, respectively. (*P < 0.0005 in comparison to sedentary C57BL/6 mice, post-hoc analysis after one-way ANOVA, #P < 0.005 in comparison to sedentary C57BL/6 mice, Student’s t-test. Arrows indicate staining outside the pinceau).

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.


Similar cation channels mediate protection from cerebellar exitotoxicity by exercise and inheritance.

Ben-Ari S, Ofek K, Barbash S, Meiri H, Kovalev E, Greenberg DS, Soreq H, Shoham S - J. Cell. Mol. Med. (2012)

Higher HCN1 and KVβ2 levels in the cerebellar pinceau of protected mice. Labelling of HCN1 (A) and KVβ2 (B) in the cerebellar pinceau of kainate-injected and exercised C57BL/6 and sedentary FVB/N mice, which show higher resistance to glutamatergic toxicity (green ∇ HCN1 or KVβ2, red ∇ calbindin-28K, n ∇ 6 for each group, insets show the pinceau region). Semi-quantification is based on percentage of HCN1 and KVβ2 immunoreactive stained areas. Control values were 0.04% and 0.4%, respectively. (*P < 0.0005 in comparison to sedentary C57BL/6 mice, post-hoc analysis after one-way ANOVA, #P < 0.005 in comparison to sedentary C57BL/6 mice, Student’s t-test. Arrows indicate staining outside the pinceau).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822931&req=5

fig04: Higher HCN1 and KVβ2 levels in the cerebellar pinceau of protected mice. Labelling of HCN1 (A) and KVβ2 (B) in the cerebellar pinceau of kainate-injected and exercised C57BL/6 and sedentary FVB/N mice, which show higher resistance to glutamatergic toxicity (green ∇ HCN1 or KVβ2, red ∇ calbindin-28K, n ∇ 6 for each group, insets show the pinceau region). Semi-quantification is based on percentage of HCN1 and KVβ2 immunoreactive stained areas. Control values were 0.04% and 0.4%, respectively. (*P < 0.0005 in comparison to sedentary C57BL/6 mice, post-hoc analysis after one-way ANOVA, #P < 0.005 in comparison to sedentary C57BL/6 mice, Student’s t-test. Arrows indicate staining outside the pinceau).
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.

Show MeSH
Related in: MedlinePlus