Shruster Adi, Offen Daniel
Laboratory of Neuroscience, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Petah Tikva, Israel.
Laboratory of Neuroscience, Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel-Aviv University, Petah Tikva, Israel.
Behav Brain Res. 2014 Mar 15;261:193-201. doi: 10.1016/j.bbr.2013.12.028. Epub 2013 Dec 31.
Alzheimer's disease (AD) affects 13% of the population over the age of 65. Behavioral and neuropsychiatric symptoms are frequent and affect 80% of patients. Adult hippocampal neurogenesis, which is impaired in AD, is involved in learning and memory. It remains unclear, however, whether increasing adult neurogenesis improves behavioral symptoms in AD. We report that in the 3xTgAD mouse model of AD, chronic Wnt3a overexpression in the ventral hippocampus dentate gyrus (DG) restored adult neurogenesis to physiological levels. The restoration of adult neurogenesis led to full recovery of danger assessment impairment and the effect was blocked by ablation of neurogenesis with X-irradiation. Finally, using a bed nucleus of stria terminalis (BNST) mRNA expression array, we found that the expression of the 5-HT1A receptor in 3xTgAD mice is selectively decreased and normalized by Wnt3a overexpression in the ventral hippocampus DG, and this normalization is neurogenesis dependent. These findings indicate that reestablishing a functional population of hippocampal newborn neurons in adult AD mice rescues behavioral symptoms, suggesting that adult neurogenesis may be a promising therapeutic target for alleviating behavioral deficits in AD patients.
阿尔茨海默病（AD）影响着13%的65岁以上人群。行为和神经精神症状很常见，影响着80%的患者。成年海马神经发生在AD中受损，它参与学习和记忆。然而，增加成年神经发生是否能改善AD的行为症状仍不清楚。我们报告，在AD的3xTgAD小鼠模型中，腹侧海马齿状回（DG）中慢性Wnt3a过表达将成年神经发生恢复到生理水平。成年神经发生的恢复导致危险评估损伤完全恢复，并且这种效应被X射线照射消除神经发生所阻断。最后，使用终纹床核（BNST）mRNA表达阵列，我们发现3xTgAD小鼠中5-HT1A受体的表达选择性降低，而腹侧海马DG中Wnt3a过表达使其正常化，并且这种正常化依赖于神经发生。这些发现表明，在成年AD小鼠中重建功能性的海马新生神经元群体可挽救行为症状，这表明成年神经发生可能是缓解AD患者行为缺陷的一个有前景的治疗靶点。
