Rotenone induces regionally distinct α-synuclein protein aggregation and activation of glia prior to loss of dopaminergic neurons in C57Bl/6 mice.

Rotenone is a naturally occurring insecticide that inhibits mitochondrial complex I and leads to neurochemical and neuropathological deficits closely resembling those in Parkinson's disease (PD). Deficits include loss of dopaminergic neurons (DAn) in the substantia nigra pars compacta (SNpc), decreased dopamine levels and aggregation of misfolded alpha-synuclein (p129). In rat models of rotenone-induced parkinsonism, the progression of neuronal injury has been associated with activation of microglia and astrocytes.

Astrocyte inflammatory signaling mediates α-synuclein aggregation and dopaminergic neuronal loss following viral encephalitis.

Viral infection of the central nervous system (CNS) can cause lasting neurological decline in surviving patients and can present with symptoms resembling Parkinson's disease (PD). The mechanisms underlying postencephalitic parkinsonism remain unclear but are thought to involve increased innate inflammatory signaling in glial cells, resulting in persistent neuroinflammation. We therefore studied the role of glial cells in regulating neuropathology in postencephalitic parkinsonism by studying the involvement of astrocytes in loss of dopaminergic neurons and aggregation of α-synuclein protein following infection with western equine encephalitis virus (WEEV).

Mitochondrial Dysfunction in Astrocytes: A Role in Parkinson's Disease?

Mitochondrial dysfunction is a hallmark of Parkinson's disease (PD). Astrocytes are the most abundant glial cell type in the brain and are thought to play a pivotal role in the progression of PD. Emerging evidence suggests that many astrocytic functions, including glutamate metabolism, Ca signaling, fatty acid metabolism, antioxidant production, and inflammation are dependent on healthy mitochondria.

Manganese exposure in juvenile C57BL/6 mice increases glial inflammatory responses in the substantia nigra following infection with H1N1 influenza virus.

Infection with Influenza A virus can lead to the development of encephalitis and subsequent neurological deficits ranging from headaches to neurodegeneration. Post-encephalitic parkinsonism has been reported in surviving patients of H1N1 infections, but not all cases of encephalitic H1N1 infection present with these neurological symptoms, suggesting that interactions with an environmental neurotoxin could promote more severe neurological damage. The heavy metal, manganese (Mn), is a potential interacting factor with H1N1 because excessive exposure early in life can induce long-lasting effects on neurological function through inflammatory activation of glial cells.

The Parkinson's disease-associated gene ITPKB protects against α-synuclein aggregation by regulating ER-to-mitochondria calcium release.

Inositol-1,4,5-triphosphate (IP) kinase B (ITPKB) is a ubiquitously expressed lipid kinase that inactivates IP, a secondary messenger that stimulates calcium release from the endoplasmic reticulum (ER). Genome-wide association studies have identified common variants in the ITPKB gene locus associated with reduced risk of sporadic Parkinson's disease (PD). Here, we investigate whether ITPKB activity or expression level impacts PD phenotypes in cellular and animal models.

NF-κB Signaling in Astrocytes Modulates Brain Inflammation and Neuronal Injury Following Sequential Exposure to Manganese and MPTP During Development and Aging.

Chronic exposure to manganese (Mn) is associated with neuroinflammation and extrapyramidal motor deficits resembling features of Parkinson's disease. Activation of astrocytes and microglia is implicated in neuronal injury from Mn but it is not known whether early life exposure to Mn may predispose glia to more severe inflammatory responses during aging. We therefore examined astrocyte nuclear factor kappa B (NF-κB) signaling in mediating innate immune inflammatory responses during multiple neurotoxic exposures spanning juvenile development into adulthood.

Infection with mosquito-borne alphavirus induces selective loss of dopaminergic neurons, neuroinflammation and widespread protein aggregation.

Neuroinvasive infections with mosquito-borne alphaviruses such as Western equine encephalitis virus (WEEV) can cause post-encephalitic parkinsonism. To understand the mechanisms underlying these neurological effects, we examined the capacity of WEEV to induce progressive neurodegeneration in outbred CD-1 mice following non-lethal encephalitic infection. Animals were experientally infected with recombinant WEEV expressing firefly luciferase or dsRed (RFP) reporters and the extent of viral replication was controlled using passive immunotherapy.

A Comparative Study of Serum Biochemistry, Metabolome and Microbiome Parameters of Clinically Healthy, Normal Weight, Overweight, and Obese Companion Dogs.

The aim of this study was to compare fecal microbiome, plasma, fecal and urine metabolomes, and serum biochemistry of adult companion dogs according to body condition scores. Blood, serum/plasma, urine, and fecal samples were collected from 66 clinically healthy, adult companion dogs of either normal weight (NW), overweight (OW), or obese dogs (OB). analyses included fecal microbiome analyses via 16S ribosomal RNA gene amplicon; sequencing, nontargeted plasma, fecal, and urine metabolomics using liquid chromatography/gas chromatography-mass; spectrometry, and serum biochemistry for each dog.