Abstract
Cognitive impairment and behavioral disparities are the distinctive baseline features to investigate in most animal models of neurodegenerative disease. However, neuronal complications are multifactorial and demand a suitable animal model to investigate their underlying basal mechanisms. By contrast, the numerous existing neurodegenerative studies have utilized various animal strains, leading to factual disparity. Choosing an optimal mouse strain for preliminary assessment of neuronal complications is therefore imperative. In this study, we systematically compared the behavioral, cognitive, cholinergic, and inflammatory impairments of outbred ICR and inbred C57BL/6 mice strains subject to scopolamine-induced amnesia. We then extended this study to the sub-strains C57BL/6N and C57BL/6J, where in addition to the above-mentioned parameters, their endogenous antioxidant levels and cAMP response-element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) protein expression were also evaluated. Compared with the ICR strain, the scopolamine-inflicted C57BL/6 strains exhibited a substantial reduction of spontaneous alternation and an approximately two-fold increase in inflammatory protein expression, compared to the control group. Among the sub-strains, scopolamine-treated C57BL/6N strains exhibited declined step-through latency, elevated acetylcholinesterase (AChE) activity and inflammatory protein expression, associated with reduced endogenous antioxidant levels and p-CREB/BDNF expression, compared to the control and tacrine-treated groups. This indicates that the C57BL/6N strains exhibit significantly enhanced scopolamine-induced neuronal impairment compared to the other evaluated strains.
Highlights
Neurodegenerative diseases can be defined as genetic and erratic conditions characterized by progressive nervous system dysfunction
Accumulating evidence suggests the crucial role of the cAMP response-element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathway, which has been associated with numerous neurodegenerative complications [13,14,15]
In addition to the above-discussed parameters, we comparatively evaluated the sub-strains C57BL/6N and C57BL/6J for modulations associated with cognitive functions such as inflammatory protein expression, endogenous antioxidant levels, and CREB/BDNF protein expression at the hippocampus
Summary
Neurodegenerative diseases can be defined as genetic and erratic conditions characterized by progressive nervous system dysfunction. Accumulating evidence suggests the crucial role of the cAMP response-element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathway, which has been associated with numerous neurodegenerative complications [13,14,15]. These aspects of the clinical phenotype should be considered when choosing the animal strain for a particular model of disease. In this study, we initially screened the inbred and outbred mouse strains based on exploratory behavior toward new environments (i.e., Y-Maze spontaneous alternation), a learning and memory task (i.e., passive avoidance test), and variation in cholinergic system (acetylcholinesterase activity) at the hippocampus. This study delivers guidance on determining suitable strains, paving the way for analogous scientific investigations into biological mechanisms involved in scopolamine-induced amnesia with possible relevance to major neurodegenerative disorders
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