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Ethanol exposure induces neonatal neurodegeneration by enhancing CB1R Exon1 histone H4K8 acetylation and up-regulating CB1R function causing neurobehavioral abnormalities in adult mice.

Subbanna S, Nagre NN, Umapathy NS, Pace BS, Basavarajappa BS - Int. J. Neuropsychopharmacol. (2014)

Bottom Line: We found that ethanol treatment of P7 mice enhances acetylation of H4 on lysine 8 (H4K8ace) at CB1R exon1, CB1R binding as well as the CB1R agonist-stimulated GTPγS binding in the hippocampus and neocortex, two brain regions that are vulnerable to ethanol at P7 and are important for memory formation and storage, respectively.We also found that ethanol inhibits cyclic adenosine monophosphate response element-binding protein (CREB) phosphorylation and activity-regulated cytoskeleton-associated protein (Arc) expression in neonatal and adult mice.The blockade or genetic deletion of CB1Rs prior to ethanol treatment at P7 rescued CREB phosphorylation and Arc expression.

View Article: PubMed Central - PubMed

Affiliation: Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY (Drs Subbanna, Nagre, and Basavarajappa); Vascular Biology Center, Georgia Regents University, Augusta, GA (Dr Umapathy); Department of Pediatrics, Georgia Regents University, Augusta, GA (Dr Pace); New York State Psychiatric Institute, New York, NY (Dr Basavarajappa); Department of Psychiatry, College of Physicians & Surgeons, Columbia University, New York, NY (Dr Basavarajappa).

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SR pretreatment rescues and CB1RKO provides protection against P7 ethanol-induced social recognition memory loss in adult mice. The percentage of social investigation is shown for S+V-, E+V-, S+SR-, and E+ SR-treated mice at 1h (a) and 24h (b) after the first encounter with the same juvenile mouse. ***p < 0.001 vs. S + V; # p < 0.05 vs. E + V. The percentage of social investigation is shown for S+CB1RWT, E+CB1RWT, S+CB1RKO, and E+CB1RKO mice at 1h (c) and 24h (d) after the first encounter with the same juvenile mouse. Each point is the mean ± SEM (n = 8 mice/group). Two-way ANOVA with Bonferroni’s post hoc test: ***p < 0.001 vs. CB1RWT + S; #p < 0.05 vs. CB1RWT + E.
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Figure 9: SR pretreatment rescues and CB1RKO provides protection against P7 ethanol-induced social recognition memory loss in adult mice. The percentage of social investigation is shown for S+V-, E+V-, S+SR-, and E+ SR-treated mice at 1h (a) and 24h (b) after the first encounter with the same juvenile mouse. ***p < 0.001 vs. S + V; # p < 0.05 vs. E + V. The percentage of social investigation is shown for S+CB1RWT, E+CB1RWT, S+CB1RKO, and E+CB1RKO mice at 1h (c) and 24h (d) after the first encounter with the same juvenile mouse. Each point is the mean ± SEM (n = 8 mice/group). Two-way ANOVA with Bonferroni’s post hoc test: ***p < 0.001 vs. CB1RWT + S; #p < 0.05 vs. CB1RWT + E.

Mentions: The social investigation results revealed that ethanol-treated mice exhibited significantly-reduced short-term (Figure 9a) and long-term (Figure 9b) SRM performance compared to saline-treated mice. Two-way ANOVA revealed that SR pretreatment rescued ethanol-induced short-term (F3,21 = 18, p < 0.01) and long-term (F3,21 = 14, p < 0.01) SRM deficits compared to ethanol-treated mice. In addition, SR alone had no significant effects (p > 0.05) on SRM, and these mice exhibited normal SRM. Ethanol failed to impair SRM in CB1RKO mice, and KO mice exhibited normal SRM (Figure 9c and d).


Ethanol exposure induces neonatal neurodegeneration by enhancing CB1R Exon1 histone H4K8 acetylation and up-regulating CB1R function causing neurobehavioral abnormalities in adult mice.

Subbanna S, Nagre NN, Umapathy NS, Pace BS, Basavarajappa BS - Int. J. Neuropsychopharmacol. (2014)

SR pretreatment rescues and CB1RKO provides protection against P7 ethanol-induced social recognition memory loss in adult mice. The percentage of social investigation is shown for S+V-, E+V-, S+SR-, and E+ SR-treated mice at 1h (a) and 24h (b) after the first encounter with the same juvenile mouse. ***p < 0.001 vs. S + V; # p < 0.05 vs. E + V. The percentage of social investigation is shown for S+CB1RWT, E+CB1RWT, S+CB1RKO, and E+CB1RKO mice at 1h (c) and 24h (d) after the first encounter with the same juvenile mouse. Each point is the mean ± SEM (n = 8 mice/group). Two-way ANOVA with Bonferroni’s post hoc test: ***p < 0.001 vs. CB1RWT + S; #p < 0.05 vs. CB1RWT + E.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 9: SR pretreatment rescues and CB1RKO provides protection against P7 ethanol-induced social recognition memory loss in adult mice. The percentage of social investigation is shown for S+V-, E+V-, S+SR-, and E+ SR-treated mice at 1h (a) and 24h (b) after the first encounter with the same juvenile mouse. ***p < 0.001 vs. S + V; # p < 0.05 vs. E + V. The percentage of social investigation is shown for S+CB1RWT, E+CB1RWT, S+CB1RKO, and E+CB1RKO mice at 1h (c) and 24h (d) after the first encounter with the same juvenile mouse. Each point is the mean ± SEM (n = 8 mice/group). Two-way ANOVA with Bonferroni’s post hoc test: ***p < 0.001 vs. CB1RWT + S; #p < 0.05 vs. CB1RWT + E.
Mentions: The social investigation results revealed that ethanol-treated mice exhibited significantly-reduced short-term (Figure 9a) and long-term (Figure 9b) SRM performance compared to saline-treated mice. Two-way ANOVA revealed that SR pretreatment rescued ethanol-induced short-term (F3,21 = 18, p < 0.01) and long-term (F3,21 = 14, p < 0.01) SRM deficits compared to ethanol-treated mice. In addition, SR alone had no significant effects (p > 0.05) on SRM, and these mice exhibited normal SRM. Ethanol failed to impair SRM in CB1RKO mice, and KO mice exhibited normal SRM (Figure 9c and d).

Bottom Line: We found that ethanol treatment of P7 mice enhances acetylation of H4 on lysine 8 (H4K8ace) at CB1R exon1, CB1R binding as well as the CB1R agonist-stimulated GTPγS binding in the hippocampus and neocortex, two brain regions that are vulnerable to ethanol at P7 and are important for memory formation and storage, respectively.We also found that ethanol inhibits cyclic adenosine monophosphate response element-binding protein (CREB) phosphorylation and activity-regulated cytoskeleton-associated protein (Arc) expression in neonatal and adult mice.The blockade or genetic deletion of CB1Rs prior to ethanol treatment at P7 rescued CREB phosphorylation and Arc expression.

View Article: PubMed Central - PubMed

Affiliation: Division of Analytical Psychopharmacology, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY (Drs Subbanna, Nagre, and Basavarajappa); Vascular Biology Center, Georgia Regents University, Augusta, GA (Dr Umapathy); Department of Pediatrics, Georgia Regents University, Augusta, GA (Dr Pace); New York State Psychiatric Institute, New York, NY (Dr Basavarajappa); Department of Psychiatry, College of Physicians & Surgeons, Columbia University, New York, NY (Dr Basavarajappa).

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Related in: MedlinePlus