Mesenchymal Stem Cells and Begacestat Mitigate Amyloid-β 25–35-Induced Cognitive Decline in Rat Dams and Hippocampal Deteriorations in Offspring

Alzheimer’s disease (AD) is the most common cause of age-related neurodegeneration and cognitive decline. AD more commonly occurs in females than males, so it necessary to consider new treatments specifically targeting this population. The present study investigated protective effects Begacestat (γ-secretase inhibitor-953, GSI-953) bone marrow-derived mesenchymal stem cells (BM-MSCs) during pregnancy on impairment rat dams offspring caused by intracerebroventricular injection Aβ 25–35 before pregnancy. performances injected with amyloid-β (Aβ 25–35) behavioral tests were significantly impaired. 25–35-injected treated BM-MSCs or GSI-953 showed a dramatically reduced number size activated microglial cells, enhancement processes length, decrease proinflammatory cytokine levels. Additionally, BM-MSC therapy 25–35-induced increases tau phosphorylation amyloid precursor protein levels neonates’ hippocampus elevated lower glycogen synthase kinase-3 brain-derived neurotrophic factor; moreover, reversed alterations gene expression neonatal hippocampus. Finally, are globally beneficial against brain alterations, particularly suppressing neural inflammation, inhibiting cell activation, restoring developmental plasticity, increasing signaling.