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Key mechanisms underlying netrin‐1 prevention of impaired spatial and object memory in Aβ 1‐42 CA1‐injected rats
Author(s) -
Zamani Elham,
Parviz Mohsen,
Roghani Mehrdad,
Mohsenimoghaddam Parvaneh
Publication year - 2019
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.13020
Subject(s) - morris water navigation task , neuroscience , impaired memory , memory impairment , netrin , medicine , amyloid precursor protein , hippocampus , alzheimer's disease , psychology , disease , cognition , axon guidance , axon
Summary Alzheimer's disease ( AD ) is a neurodegenerative disorder with an incompletely defined aetiology that is associated with memory and cognitive impairment. Currently available therapeutics only provide temporary assistance with symptoms. In spite of plentiful research in the field and the generation of thousands of studies, much is still to be clarified on precise mechanisms of pathobiology, prevention modalities, disease course and cure. Netrin‐1, a laminin family protein, is said to have anti‐inflammatory and anti‐apoptotic effects and has a key role in neurogenesis and morphogenesis of neural structures. Accordingly, this study was designed to investigate protective effects of bilateral intrahippocampal fissure microinjections of netrin‐1 on memory impairment in rat model of AD . Concomitant administration of netrin‐1 with amyloid beta 1‐42 (Aβ 1‐42 ) improved cognitive dysfunction in novel object recognition task ( NOR ), ameliorated impaired spatial memory in Morris water maze ( MWM ) setting, increased neuronal density and reduced amyloid aggregation in rat AD model. Netrin‐1 was also seen to prevent Aβ 1‐42 ‐induced caspase‐3, caspase‐7 and NF ‐κB (nuclear factor kappa‐light‐chain‐enhancer of activated B cells) activation. Therefore, based on the data reported here, netrin‐1 may be a promising biologic therapeutic that addresses the memory and neuronal loss associated with AD .