Aβ increases neural stem cell activity in senescence-accelerated SAMP8 mice

Area of Science:

• Neuroscience
• Cell Biology
• Aging Research

Background:

• Neurogenesis, the creation of new neurons, continues in the adult brain as neural stem cells (NSCs) provide plasticity.
• While changes in neurogenesis are noted in transgenic Alzheimer's disease (AD) models, its role in sporadic AD remains unclear.
• The SAMP8 mouse strain models the aging process and the transition to AD-like pathology without genetic modification.

Purpose of the Study:

• To investigate NSC activity and neurogenesis in a non-transgenic model of sporadic Alzheimer's disease (AD).
• To explore the early changes in NSC proliferation preceding AD-like symptoms in the SAMP8 mouse model.

Main Methods:

• Analysis of NSC proliferation in the forebrain of SAMP8 mice at different aging stages.
• In vitro studies to assess the impact of amyloid beta 1-42 (Aβ(1-42)) and PI3K signaling on NSC proliferation.
• Correlation of NSC proliferation with AD-related markers like Aβ(1-42) levels and gliosis.

Main Results:

• A significant, transient increase in NSC proliferation was observed in the forebrain of SAMP8 mice.
• This proliferation surge occurred before the rise in amyloid beta 1-42 [Aβ(1-42)] and gliosis, hallmarks of AD.
• In vitro experiments suggested that secreted Aβ(1-42) and PI3K signaling contribute to this early NSC proliferation boost.

Conclusions:

• Soluble Aβ(1-42) and PI3K signaling play a role in the autocrine regulation of NSC proliferation.
• The transient over-proliferation of NSCs precedes AD pathology and may lead to neurogenic failure later in the disease.
• Findings suggest potential therapeutic targets related to neurogenesis modulation in Alzheimer's disease.