SEMINARIO: Fernando Gordillo / Andrea Palomares

12:00 – 12:30: Fernando Gordillo

Transposable elements: new pieces in the jigsaw of sex differences in Parkinson’s disease

Abstract: Transposable elements (TEs) are common mobile genetic elements, comprising 42% of the human genome and are related with genome activity and integrity. They have recently emerged as potential contributors to Parkinson’s disease (PD); however, their role and sex specific impact remain poorly understood. We have generated a cell type resolved atlas of TE dysregulation in PD through an integrative meta analysis of TE expression across brain single-nucleus RNA seq datasets. We identified widespread TE activation across brain cell types, with marked upregulation of L1s in neurons and HERVs in oligodendrocytes. Sex stratified analyses revealed distinct male and female biased TE signatures, indicating regulatory programs uniquely affected in each sex, including MIR elements in microglia and Alu subfamilies in neurons. Correlation and genomic proximity analyses also uncovered TE-gene associations linked to important PD pathways such as neuroinflammation or myelination. Collectively, our study positions TEs as active, sex modulated contributors to PD pathology.

12:30 – 13:00: Andrea Palomares

Sex-dependent differences in cognitive function, neurotransmission and neuroinflammation

Abstract: There is extensive literature reporting sex-dependent differences in cognitive function. However, the molecular mechanisms that underly these differences remain unclear. Cognitive function is mainly modulated by glutamatergic and GABAergic neurotransmission in hippocampus. Our group has described the mechanisms by which hyperammonemia impairs cognitive function by inducing neuroinflammation which alters neurotransmission in hippocampus. Guided by our previous knowledge from the lab studies, we conducted experiments to identify sex-dependent differences in cognitive performance, glutamatergic and GABAergic neurotransmission and in neuroinflammation in hippocampus between male and female Wistar rats. The results support that increased neuroinflammation and altered IL-1β signaling in hippocampus of female rats induce changes in the membrane expression of glutamate and GABA receptors that result in reduced performance in cognitive tests.
We also studied the effects of hyperammonemia on the above processes and have found that the effects of hyperammonemia are different on male and female rats, with stronger deleterious effects on males.