Neuron and neuroblast numbers and cytogenesis in the dentate gyrus of aged APPswe/PS1dE9 transgenic mice: Effect of long-term treatment with paroxetine

Neurobiology of Disease

卷:104

Mark J. West¹  Elena V. Bouzinova²  Louise Ørum Olesen²  Ove Wiborg²  Bente Finsen³  Alicia A. Babcock³  Maurizio Severino³  Mithula Sivasaravanaparan³ 

[1]Department of Biomedicine, Health, Aarhus University, Denmark

[2]|Department of Clinical Medicine, Aarhus University, Denmark

[3]|Department of Neurobiological Research, Institute of Molecular Medicine, University of Southern Denmark, Denmark

关键词: Neurogenesis;    Hippocampus;    APP/PS1 mice;    SSRI;    Paroxetine;    Spontaneous alternation behaviour;   

DOI  :  

来源: DOAJ

【 摘 要 】

Altered neurogenesis may influence hippocampal functions such as learning and memory in Alzheimer's disease. Selective serotonin reuptake inhibitors enhance neurogenesis and have been reported to reduce cerebral amyloidosis in both humans and transgenic mice. We have used stereology to assess the longitudinal changes in the number of doublecortin-expressing neuroblasts and number of granular neurons in the dentate gyrus of APPswe/PS1dE9 transgenic mice. Furthermore, we investigated the effect of long-term paroxetine treatment on the number of neuroblasts and granular neurons, hippocampal amyloidosis, and spontaneous alternation behaviour, a measure of spatial working memory, in transgenic mice. We observed no difference in granular neurons between transgenic and wild type mice up till 18 months of age, and no differences with age in wild type mice. The number of neuroblasts and the performance in the spontaneous alternation task was reduced in aged transgenic mice. Paroxetine treatment from 9 to 18 months of age reduced hippocampal amyloidosis without affecting the number of neuroblasts or granular neurons. These findings suggest that the amyloidosis affects the differentiation of neuroblasts and spatial working memory, independent of changes in total granular neurons. Furthermore, while long-term paroxetine treatment may be able to reduce hippocampal amyloidosis, it appears to have no effect on total number of granular neurons or spatial working memory.

【 授权许可】

Unknown