Open AccessAge‐Dependent Effect of β‐Amyloid Toxicity on Basal Forebrain Cholinergic Neurons and Inflammation in the Rat Brain
Author(s) -
Nell Hayley Joy,
Whitehead Shawn Narain,
Cechetto David Floyd
Publication year - 2015
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12199
Subject(s) - neuroinflammation , basal forebrain , cholinergic , hippocampal formation , cholinergic neuron , neuroscience , forebrain , medicine , endocrinology , biology , inflammation , central nervous system
Beta‐amyloid ( A β) accumulation, neuroinflammation, basal forebrain cholinergic loss and hippocampal degeneration are well‐described pathologies associated with A lzheimer's disease ( AD ). However, the role that age plays in the susceptibility of the brain to these AD pathologies and the relationships between them is still not well understood. This study investigated the age‐related response to intracerebroventricular injection of A β 25–35 in 3‐, 6‐ and 9‐month‐old rats. A β toxicity resulted in an age‐related increase in cholinergic loss and microglial activation in the basal forebrain along with neuronal loss in the hippocampal CA 3 subfield. Performance in the M orris water maze revealed impairments in long‐term reference memory in 6‐month‐old A β administered animals, which was not seen in 3‐month‐old animals. These results support a role of A β administration in inducing age‐dependent cholinergic loss and neuroinflammation, and additionally provide evidence for a more age‐appropriate model of adult‐onset A β toxicity demonstrating pathological changes that reflect the early stages of AD pathogenesis including neuroinflammation, cholinergic loss and beginning stages of memory impairment.