|Ingram TL, Shephard F, Sarmad S, Ortori CA, Barrett DA and Chakrabarti L (2020) Sex differences characterise inflammatory profiles of cerebellar mitochondria and are attenuated in Parkinson’s disease. MitoFit Preprint Arch 2020.2 doi:10.26124/mitofit:200002.|
Abstract: Version 1 (v1) 2020-04-30 doi:10.26124/mitofit:200002
Response to inflammation is a key determinant in many diseases and their outcomes. Diseases that commonly affect older people are frequently associated with altered inflammatory processes. Neuroinflammation has been described in Parkinson’s disease (PD) brain and presents a potential therapeutic target. PD is characterised by the loss of dopaminergic neurons in the substantia nigra pars compacta and at the sub-cellular level, mitochondrial dysfunction is a key feature. However, there is evidence that a different region of the brain, the cerebellum, is involved in the pathophysiology of PD. We report relative levels of 40 pro- and anti-inflammatory cytokines measured in PD and control cerebellar mitochondria. These data were obtained by screening cytokine antibody arrays. In parallel, we present concentrations of 29 oxylipins and 4 endocannabinoids measured in mitochondrial fractions isolated from post-mortem PD cerebellum with age and sex matched controls. Our oxylipin and endocannabinoid data were acquired via quantitation by LC-ESI--MS/MS. The separate sample sets both show there are clearly different inflammatory profiles between the sexes in control samples. Sex specific profiles were not maintained in cerebellar mitochondria isolated from PD brains. One interpretation of our findings is that normally females have a wide-ranging inflammatory profile that can respond to or absorb the effects of increased levels of cytokines and oxylipins. These observations may have implications for other inflammatory diseases where the sexes are affected unequally in number or severity.
• Keywords: Inflammation, Parkinson's disease, cerebellar mitochondria, sex differences • Bioblast editor: Iglesias-Gonzalez J
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