Mechanisms of Neuronal Death in the Cerebral Cortex during Aging and Development of Alzheimer’s Disease-Like Pathology in Rats

Abstract

Alzheimer’s disease (AD) is the commonest type of late-life dementia and damages the cerebral cortex, a vulnerable brain region implicated in memory, emotion, cognition, and decision-making behavior. AD is characterized by progressive neuronal loss, but the mechanisms of cell death at different stages of the disease remain unknown. Here, by means of OXYS rats as an appropriate model of the most common (sporadic) AD form, we studied the main pathways of cell death during development of AD-like pathology, including the preclinical stage. We found that apoptosis is activated at the pre-symptomatic stage (age 20 days) correlating with the retardation of brain development in the OXYS strain early in life. Progression of the AD-like pathology was accompanied by activation of apoptosis and necroptosis resulting from a decline of autophagy-mediated proteostasis. Our results are consistent with the idea that the nature of changes in the pathways of apoptosis, autophagy, and necrosis depends on the stage of AD.

Alterations of STEP46 and STEP61 Expression in the Rat Retina with Age and AMD-Like Retinopathy Development

“…In OXYS rats, STEP levels increased in the retina by the age of 20 days in parallel with increased colocalization of proBDNF and p75NTR proteins [ 18 ] and an increase in apoptosis [ 16 ]. Similar alterations of BDNF expression and apoptosis have been registered in the cortex [ 32 , 33 ] and hippocampus [ 34 ] of OXYS rats at age 20 days. These features of OXYS rats’ phenotype may be related to the retardation of CNS development in OXYS rats at an early age.…”

Qingxin Kaiqiao Fang Inhibits Aβ25-35‐Induced Apoptosis in Primary Cultured Rat Hippocampal Neuronal Cells via the p38 MAPK Pathway: An Experimental Validation and Network Pharmacology Study

“…Neuronal apoptosis, which is an important cell process and the main mechanism of neuronal death, plays an essential role in neurodegeneration in AD. The significance of apoptosis in the pathogenesis of AD has attracted increasing attention [ 16 ]. In a normal physiological environment, apoptosis and the natural antiapoptotic defense system exist in a dynamic balance and the excessive accumulation and deposition of A β disrupt this balance [ 17 ].…”

Overexpression of NREP Promotes Migration and Invasion in Gastric Cancer Through Facilitating Epithelial-Mesenchymal Transition

“…The TUNEL apoptosis detection kit was used to perform the TUNEL assay, as described previously ( Telegina et al, 2019 ). TUNEL-negative (blue) and TUNEL-positive (red) cells were observed using a fluorescence microscope (Olympus CKX-41, Japan; ×200 magnification).…”