LOU/c/Jall rat as a resilience model in the context of sporadic Alzheimer’s disease induced by streptozotocin

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by early decline in episodic and spatial memory, associated with accumulation of brain markers. Intriguingly, despite similar levels of brain alteration, some elderly subjects show less cognitive impairment than others. To explain this lack of correlation between the degree of brain lesions and the severity of cognitive symptoms, the concept of cognitive resilience (CR) has emerged. Yet, the protective mechanisms supporting CR remain poorly understood. To tackle this issue, we developed a preclinical model of CR. Our model is based on the use of a sporadic form model of AD in a particular strain of rat, described as a model of successful aging (LOU/c/jall rats). Seventy-five adult male rats (Lou/c/Jall and Wistar as control) were bilaterally injected with streptozotocin (STZ; 3 mg/kg) or a vehicle (aCSF) solution in the cerebral ventricles. One month post-injection, cognitive behavioral performances were evaluated and then a neuropathological investigation was conducted. Results indicate that STZ treatment did not affect locomotor activity or anxiety-like behavior, regardless of the strain considered. Conversely, STZ induced spatial working memory and recognition memory deficits in both strains. Interestingly enough, more severe deficits were observed in the Wistar strain. Currently in process, immunohistochemical analysis and cerebral assays of the neuropathological markers should provide a better understanding of the proteomic expression neurobiological mechanisms underlying the CR seen in LOU/c/jall rats and may offer new insights into the search for new therapeutic targets for AD.