Gender-specific brain regional variation of neurons, endogenous estrogen, neuroinflammation and glial cells during rotenone-induced mouse model of Parkinson's disease

Rotenone (RT) produces reactive oxygen species (ROS) by inhibiting the mitochondrial electron transport chain; causing dopaminergic (DA) cell death in the substantia nigra (SN) and simulates other models of induced Parkinson's disease (PD). There is a sincere dearth of knowledge regarding the status of glial cells, neuroprotective estrogen and the status of neuroinflammatory TNF-α in the different brain regions in either sex during healthy, as well as during PD conditions. In the present study of RT-induced mouse model of PD, we have selected the frontal cortex (FC), hippocampus (HC) and SN from either sex of Swiss albino mice as these are the major regions involved during PD pathogenesis.During non pathogenic conditions, the ROS-scavenging enzyme activity varied among the brain regions and also in between genders. The number of DOPA decarboxylase-positive cells, astrocytes and microglia was similar in the respective regions of the brain in both the sexes. The level of proinflammatory cytokine TNF-α was same in the respective FC and HC in either sex except that of SN. The expression level of estrogen and its receptors varied among the three brain regions. During RT treatment, ROS-scavenging enzyme activities increased, DOPA decarboxylase-positive neurons and fibers in DA as well as in norepinephrinergic (NE) systems become degenerated, number of astrocytes decreased and microglial cells increased in those specific brain regions in either of the sexes except in the SN region of males where astrocyte number remained unaltered and microglial cell percentage decreased. TNF-α increased in the FC and SN but remained unaltered in the HC of both sexes. Estradiol level decreased in the HC and SN but the level unevenly varied in the FC. Similarly, the estrogen bound and nuclear-cytosolic receptor α and β also varied differentially among the brain regions of the two sexes.Therefore our present study depicts that there exists a clear variation of neuronal and astroglial cell population, estrogen and its receptor levels in different brain regions of both the sexes during control and RT-treated pathogenic condition and these variations have major implication in PD pathogenesis and progression.