Poster Presentation ESA-SRB-APEG-NZSE 2022

Many diseases show sex differences in incidence, progression or age of onset. Sex differences imply that one sex has hormones (gonadal testosterone and oestrogen) or sex chromosomes (X,Y) that protect from or exacerbate disease risk relative to the other sex. Parkinson’s disease (PD) is caused by the progressive death of dopaminergic neurons in the substantia nigra that control the voluntary movement affects twice as many men than women. Men with PD also experience steeper decline and greater neuronal degeneration and denervation and mitochondrial damage. There is no cure for PD, or drug that prevents neurodegeneration. Prevailing dogma is that estrogen is neuroprotective in females. In rat models, we identified male exacerbate factor SRY. Therefore, there is a need to understand the relative effects of hormones and/or sex chromosomes to disease risk.

Our “Four Core Genotypes (FCG)” rat model (Abstract 85805 and Figure) allows us to measure simultaneously the effect of sex hormone or sex chromosome and interactive effects in any rat model of physiology, disease or drug response. To explain sex differences, rats have advantages over mice especially they have better performance in behaviour tests and their larger size are preferred for procedures like stereotactic surgery and telemetry. Following a single intranigral injection of 6-OHDA or rotenone or vehicle into FCG rats [n=30 rats per group]. Motor function will be assessed weekly by the limb use asymmetry and amphetamine-induced rotation tests. At the end of the weekly behavioural tests, rat brains (n=5 per group) will be isolated and processed for measurement of nigrostriatal gene expression by RNAseq, protein expression (Western blot), immunohistochemistry and stereology to quantifying the loss of dopamine neurons on right versus left side of the nigra.