Sex specific inflammatory profiles of cerebellar mitochondria are attenuated in Parkinson’s disease

Abstract

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. PD is characterized 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.

The Roles of Optogenetics and Technology in Neurobiology: A Review

“… Steinbeck et al (2015) induced rapid and reversible reactivation of motor defects in mice that had recovered from Parkinson’s motor defects induced by injury ( Figure 3 ). And a recent study showed that photogenetic stimulation of the deep brain can relieve Parkinson’s disease in rats ( Ingram et al, 2020 ; Yu et al, 2020 ). These studies suggest that optogenetics has great potential in the clinical treatment of Parkinson’s disease.…”

The dysregulated Pink1- Drosophila mitochondrial proteome is partially corrected with exercise

“…Early studies into the effect of α-synuclein (SNCA) gene deletion on lipid metabolism in mice reported reduced palmate uptake and altered palmate metabolism in the brain, reduced acyl-CoA Synthetase activity that resulted in reduced arachidonic acid uptake and turnover, and increased docosahexaenoic acid brain mass, incorporation and turnover [58][59][60]. Our own work shows differences in arachidonic acid derivatives in Parkinson's disease mitochondria [61].…”

The dysregulated Pink1-Drosophila mitochondrial proteome is partially corrected with exercise

“…Early studies into the effect of α-synuclein (SNCA) gene deletion on lipid metabolism in mice reported reduced palmate uptake and altered palmate metabolism in the brain, reduced acyl-CoA Synthetase activity that resulted in reduced arachidonic acid uptake and turnover, and increased docosahexaenoic acid brain mass, incorporation and turnover (Golovko et al, 2005(Golovko et al, , 2006(Golovko et al, , 2007. Our own work shows differences in arachidonic acid derivatives in Parkinson's disease mitochondria (Ingram et al, 2020).…”