Sex differences in disease progression and epigenetic resilience in a mouse model of VCID
Vascular cognitive impairment and dementia (VCID) is a cerebrovascular disease state which has chronic cerebral hypoperfusion (CCH) as a main contributor to its pathology. VCID exhibits sexual dimorphisms in humans, and it is often characterized by a mechanism of chronic inflammation secondary to CCH in mouse models. Previous work in our lab showed that mice induced with vascular cognitive VCID secondary to CCH are resilient to the memory loss associated with this cerebrovascular disease when treated with repetitive hypoxic conditioning (RHC). This resilience can be transmitted intergenerationally, from parent mice (F0) treated with RHC, to their untreated offspring (F1). CCH-induced VCID in mice has yet to be examined by sex with respect to disease severity, as well as in response to a treatment such as RHC. Thus, we sought to explore a sexual dimorphism in VCID with respect to impairments in spatial memory (Y-Maze Test) and reference memory (Novel Object Recognition (NOR) Test), and with respect to levels of the inflammatory cytokines IL-1ꞵ, IL-6, and TNF-ɑ and IFN-γ in F1-generation mice. No evidence of a sexual dimorphism was found based on outcomes of the Y-Maze Test, NOR Test, or cytokine expression. Various confounding variables have resulted in much of my findings being inconclusive to date (some are still underway at the time this thesis was submitted). More extensive studies with many more mice are ultimately needed to confirm the presence or absence of sexual dimorphism in VCID disease; if documented, then future treatments can be tailored in a sex-specific manner.