A beta increases neural stem cell activity in senescence-accelerated SAMP8 mice

作者：Diaz Moreno Maria; Hortigueela Rafael; Goncalves Ania; Garcia Carpio Irmina; Manich Gemma; Garcia Bermudez Edurne; Moreno Estelles Mireia; Eguiluz Cesar; Vilaplana Jordi; Pelegri Carme; Vilar Marcal; Mira Helena^*

来源：Neurobiology of Aging, 2013, 34(11): 2623-2638.

DOI：10.1016/j.neurobiolaging.2013.05.011

• Neural stem cell
• Subventricular zone
• Olfactory bulb
• Amyloid beta
• Neurogenesis
• Neurosphere
• Alzheimer%26apos
• s disease
• Senescence-accelerated mouse
• SAMP8

Neurogenesis persists in the adult brain as a form of plasticity due to the existence of neural stem cells (NSCs). Alterations in neurogenesis have been found in transgenic Alzheimer%26apos;s disease (AD) mouse models, but NSC activity and neurogenesis in sporadic AD models remains to be examined. We herein describe a remarkable increase in NSC proliferation in the forebrain of SAMP8, a non-transgenic mouse strain that recapitulates the transition from healthy aging to AD. The increase in proliferation is transient, precedes AD-like symptoms such as amyloid beta 1-42 [A beta(1-42)] increase or gliosis, and is followed by a steep decline at later stages. Interestingly, in vitro studies indicate that secreted A beta(1-42) and PI3K signaling may account for the early boost in NSC proliferation. Our results highlight the role of soluble A beta(1-42) peptide and PI3K in the autocrine regulation of NSCs, and further suggest that over-proliferation of NSCs before the appearance of AD pathology may underlie neurogenic failure during the age-related progression of the disease. These findings have implications for therapeutic approaches based on neurogenesis in AD.

• 出版日期2013-11