Mechanistic Insights Into Parkinson’s Disease and Sex Differences in Liver Oxidative Stress

In volume transmission, or neuromodulation, neurons communicate not through direct, one-to-one synaptic connections, but by releasing neurotransmitters broadly into the extracellular space from numerous varicosities. This type of signaling is particularly relevant for serotonin and dopamine neurons, which project from the dorsal raphe and substantia nigra, respectively, to the hippocampus. In the first part of my talk, I will discuss recent findings on their interplay in the brain and how this makes serotonin a potential biomarker for Parkinson’s disease. The second part will focus on sex differences in oxidative stress management in peripheral tissues such as the liver. Women generally have lower oxidative stress and higher glutathione levels than men, reflecting the influence of sex hormones. Using mathematical modeling, I explore the mechanisms underlying these differences and why estrogen supplementation has differential effects on a key cardiovascular biomarker in pre- versus post-menopausal women. By linking clinical data with modeling, this work provides insights into the underlying biology and informs sex- and menopausal status-specific approaches in medicine.