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Targeting neurogenesis ameliorates danger assessment in a mouse model of Alzheimer's disease
- Source :
- Behavioural Brain Research. 261:193-201
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- 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.
- Subjects :
- Neurogenesis
Genetic Vectors
Population
Hippocampus
Mice, Transgenic
tau Proteins
Hippocampal formation
Wnt3 Protein
Amyloid beta-Protein Precursor
Mice
Behavioral Neuroscience
Alzheimer Disease
Presenilin-1
Animals
Humans
Maze Learning
Receptor
education
5-HT receptor
Neurons
education.field_of_study
Dentate gyrus
Mice, Inbred C57BL
Disease Models, Animal
Stria terminalis
Gene Expression Regulation
Phosphopyruvate Hydratase
Mutation
Exploratory Behavior
Psychology
Neuroscience
Subjects
Details
- ISSN :
- 01664328
- Volume :
- 261
- Database :
- OpenAIRE
- Journal :
- Behavioural Brain Research
- Accession number :
- edsair.doi.dedup.....556dae8f87683fea6e14b81fa2397a7c
- Full Text :
- https://doi.org/10.1016/j.bbr.2013.12.028