Title:Amyloid-beta Induced Neurotoxicity Impairs Cognition and Adult Hippocampal Neurogenesis in a Mouse Model for Alzheimer’s Disease
VOLUME: 17 ISSUE: 11
Author(s):Sanila Amber, Sumera, Fatima J. Mirza, Muhammad Asif , Deeba Hassan, Touqeer Ahmed and Saadia Zahid*
Affiliation:Neurobiology Research Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Neurobiology Research Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Neurobiology Research Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, Neurobiology Research Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Neurobiology Research Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Neurobiology Research Laboratory, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad
Keywords:Hippocampus, neurodegeneration, neurogenesis, Alzheimer's disease, cognition, neurotoxicity.
Abstract:
Background: Neurogenesis, the key mechanism to generate new neurons from existing
stem cell niches continues throughout the life in the adult mammalian brain, although decelerate with
aging or the progression of neurodegenerative disorders like Alzheimer’s disease (AD). In the past
few years, impaired adult hippocampal neurogenesis emerged as a contributing hallmark of AD
pathophysiology along with amyloid beta (Aβ) and tau hyper phosphorylation-induced neurotoxicity.
However, no conclusive evidence exists that indicates the up/down-regulation of adult hippocampal
neurogenesis during the course of AD progression.
Methods: In this study, we examined alterations in adult hippocampal neurogenesis and cognitive
deficits using Aβ(1-42)-induced mouse model of AD.
Results: Our results demonstrate that Aβ administration induces an anxiety like behavior and impairs
spatial and non-spatial memory and learning in BALB/c mice. Extensive neuronal loss was also evident
in the dentate gyrus (DG), CA1, CA2 and CA3 regions of hippocampus in Aβ-treated animals.
Furthermore, Aβ-exposure markedly reduced the real-time expression of markers of cell proliferation
and migration i.e. Ki67 and DCX, whereas immunohistochemistry analysis revealed a substantial
reduction in the expression levels of Ki67 and NeuN.
Conclusion: Our findings highlight the association of Aβ-induced neurotoxicity with altered
neurogenesis and memory formation; however further insight is warranted to explore the underlying
molecular pathway(s). Moreover, the treatment strategies aiming to repair the adult hippocampal
neurogenesis hold potential as AD therapeutics.
