Limits...
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).

Show MeSH

Related in: MedlinePlus

Prior blockade or genetic deletion of CB1Rs prevents P7 ethanol-induced spontaneous alternation performance deficits in adult mice. (a) Total number of arm entries reflecting exploratory activities of mice in the Y-maze does not differ between S+V, E+V, S+SR, and E+SR-treated mice. (b) The time spent in each arm was not different between the four groups (p > 0.05). (c) Spatial working memory of S+V, E+V, S+SR, and E+SR-treated mice were tested by spontaneous alternation performance in the Y-maze. Note that E+V-treated mice perform poorly compared to S+V-treated controls (***p < 0.001), while E+SR treatment restores E+V levels of alternation performance (#p < 0.001 versus E+V). n = 8 mice per group. One-way ANOVA with Bonferroni’s post hoc test was used to analyze significant differences. (d) Total number of arm entries reflecting exploratory activities of mice in the Y-maze does not differ between the CB1RWT and KO with or without ethanol. (e) The time spent in each arm was not different between S+CB1RWT, E+CB1RWT, S+CB1RKO, and E+CB1RKO treated mice (p > 0.05). (f) Spontaneous alternation performance of CB1RWT and CB1RKO mice treated with or without saline or ethanol were tested in the Y-maze. Note that the performance of P7 saline-treated CB1RKO mice was significantly enhanced compared to P7 saline-treated CB1RWT mice (@p < 0.001), while ethanol failed to impair alternation performance in CB1RKO mice (#p < 0.001 vs. E + CB1RWT). n = 8 mice per group. One-way ANOVA with Bonferroni’s post hoc test was used to analyze significant differences. Each point is the mean ± SEM.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4376538&req=5

Figure 7: Prior blockade or genetic deletion of CB1Rs prevents P7 ethanol-induced spontaneous alternation performance deficits in adult mice. (a) Total number of arm entries reflecting exploratory activities of mice in the Y-maze does not differ between S+V, E+V, S+SR, and E+SR-treated mice. (b) The time spent in each arm was not different between the four groups (p > 0.05). (c) Spatial working memory of S+V, E+V, S+SR, and E+SR-treated mice were tested by spontaneous alternation performance in the Y-maze. Note that E+V-treated mice perform poorly compared to S+V-treated controls (***p < 0.001), while E+SR treatment restores E+V levels of alternation performance (#p < 0.001 versus E+V). n = 8 mice per group. One-way ANOVA with Bonferroni’s post hoc test was used to analyze significant differences. (d) Total number of arm entries reflecting exploratory activities of mice in the Y-maze does not differ between the CB1RWT and KO with or without ethanol. (e) The time spent in each arm was not different between S+CB1RWT, E+CB1RWT, S+CB1RKO, and E+CB1RKO treated mice (p > 0.05). (f) Spontaneous alternation performance of CB1RWT and CB1RKO mice treated with or without saline or ethanol were tested in the Y-maze. Note that the performance of P7 saline-treated CB1RKO mice was significantly enhanced compared to P7 saline-treated CB1RWT mice (@p < 0.001), while ethanol failed to impair alternation performance in CB1RKO mice (#p < 0.001 vs. E + CB1RWT). n = 8 mice per group. One-way ANOVA with Bonferroni’s post hoc test was used to analyze significant differences. Each point is the mean ± SEM.

Mentions: In our first behavioral test, adult mice treated with saline, ethanol (with vehicle), SR, or ethanol + SR at P7 were tested using spontaneous alternation in the Y maze. P7 ethanol, SR, or ethanol + SR treatment had no significant effect on exploratory activities assessed by the number of arm entries (Figure 7a) and time spent (Figure 7b) in each arm during Y-maze testing. Two-way ANOVA revealed that the ethanol-treated mice exhibited significantly reduced spontaneous alternation performance compared to saline-treated mice and that SR rescued these deficits (F3,21 = 10, p < 0.001; Figure 7c). Treatment with SR alone at P7 had no significant effect on spontaneous alternation performance. P7 ethanol treatment had no significant effect on the number of arm entries (Figure 7d) or the time spent in each arm (Figure 7e; exploratory activity) in either CB1RWT or KO mice. CB1RKO mice exhibited significantly enhanced spontaneous alternation behavior (p < 0.01) compared to WT mice. Notably, ethanol treatment at P7 failed to induce a spatial working memory deficit in the Y-maze test in adult CB1RKO mice (p > 0.05; Figure 7f).


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)

Prior blockade or genetic deletion of CB1Rs prevents P7 ethanol-induced spontaneous alternation performance deficits in adult mice. (a) Total number of arm entries reflecting exploratory activities of mice in the Y-maze does not differ between S+V, E+V, S+SR, and E+SR-treated mice. (b) The time spent in each arm was not different between the four groups (p > 0.05). (c) Spatial working memory of S+V, E+V, S+SR, and E+SR-treated mice were tested by spontaneous alternation performance in the Y-maze. Note that E+V-treated mice perform poorly compared to S+V-treated controls (***p < 0.001), while E+SR treatment restores E+V levels of alternation performance (#p < 0.001 versus E+V). n = 8 mice per group. One-way ANOVA with Bonferroni’s post hoc test was used to analyze significant differences. (d) Total number of arm entries reflecting exploratory activities of mice in the Y-maze does not differ between the CB1RWT and KO with or without ethanol. (e) The time spent in each arm was not different between S+CB1RWT, E+CB1RWT, S+CB1RKO, and E+CB1RKO treated mice (p > 0.05). (f) Spontaneous alternation performance of CB1RWT and CB1RKO mice treated with or without saline or ethanol were tested in the Y-maze. Note that the performance of P7 saline-treated CB1RKO mice was significantly enhanced compared to P7 saline-treated CB1RWT mice (@p < 0.001), while ethanol failed to impair alternation performance in CB1RKO mice (#p < 0.001 vs. E + CB1RWT). n = 8 mice per group. One-way ANOVA with Bonferroni’s post hoc test was used to analyze significant differences. Each point is the mean ± SEM.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4376538&req=5

Figure 7: Prior blockade or genetic deletion of CB1Rs prevents P7 ethanol-induced spontaneous alternation performance deficits in adult mice. (a) Total number of arm entries reflecting exploratory activities of mice in the Y-maze does not differ between S+V, E+V, S+SR, and E+SR-treated mice. (b) The time spent in each arm was not different between the four groups (p > 0.05). (c) Spatial working memory of S+V, E+V, S+SR, and E+SR-treated mice were tested by spontaneous alternation performance in the Y-maze. Note that E+V-treated mice perform poorly compared to S+V-treated controls (***p < 0.001), while E+SR treatment restores E+V levels of alternation performance (#p < 0.001 versus E+V). n = 8 mice per group. One-way ANOVA with Bonferroni’s post hoc test was used to analyze significant differences. (d) Total number of arm entries reflecting exploratory activities of mice in the Y-maze does not differ between the CB1RWT and KO with or without ethanol. (e) The time spent in each arm was not different between S+CB1RWT, E+CB1RWT, S+CB1RKO, and E+CB1RKO treated mice (p > 0.05). (f) Spontaneous alternation performance of CB1RWT and CB1RKO mice treated with or without saline or ethanol were tested in the Y-maze. Note that the performance of P7 saline-treated CB1RKO mice was significantly enhanced compared to P7 saline-treated CB1RWT mice (@p < 0.001), while ethanol failed to impair alternation performance in CB1RKO mice (#p < 0.001 vs. E + CB1RWT). n = 8 mice per group. One-way ANOVA with Bonferroni’s post hoc test was used to analyze significant differences. Each point is the mean ± SEM.
Mentions: In our first behavioral test, adult mice treated with saline, ethanol (with vehicle), SR, or ethanol + SR at P7 were tested using spontaneous alternation in the Y maze. P7 ethanol, SR, or ethanol + SR treatment had no significant effect on exploratory activities assessed by the number of arm entries (Figure 7a) and time spent (Figure 7b) in each arm during Y-maze testing. Two-way ANOVA revealed that the ethanol-treated mice exhibited significantly reduced spontaneous alternation performance compared to saline-treated mice and that SR rescued these deficits (F3,21 = 10, p < 0.001; Figure 7c). Treatment with SR alone at P7 had no significant effect on spontaneous alternation performance. P7 ethanol treatment had no significant effect on the number of arm entries (Figure 7d) or the time spent in each arm (Figure 7e; exploratory activity) in either CB1RWT or KO mice. CB1RKO mice exhibited significantly enhanced spontaneous alternation behavior (p < 0.01) compared to WT mice. Notably, ethanol treatment at P7 failed to induce a spatial working memory deficit in the Y-maze test in adult CB1RKO mice (p > 0.05; Figure 7f).

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).

Show MeSH
Related in: MedlinePlus