Calorie restriction (CR) enhances health span (the length of time that an organism remains healthy) and increases longevity across species. In mice, these beneficial effects are partly mediated by the lowering of core body temperature that occurs during CR. Conversely, the favorable effects of CR on health span are mitigated by elevating ambient temperature to thermoneutrality (30°C), a condition in which hypothermia is blunted.
View Article and Find Full Text PDFPHARC (polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and cataract) is a human neurological disorder caused by deleterious mutations in the gene, which encodes an integral membrane lyso-phosphatidylserine (lyso-PS) lipase. Pharmacological or genetic disruption of ABHD12 leads to higher levels of lyso-PS lipids in human cells and the central nervous system (CNS) of mice. ABHD12 loss also causes rapid rewiring of PS content, resulting in selective increases in the level of arachidonoyl (C20:4) PS and decreases in the levels of other PS species.
View Article and Find Full Text PDFThe human genes for interleukin 13 (IL-13) and its receptor alpha 1 (IL-13Rα1) are in chromosomal regions associated with Parkinson's disease (PD). The interaction of IL-13 with its receptor increases the susceptibility of mouse dopaminergic neurons to oxidative stress. We identified two rare single SNPs in IL13 and IL13RA1 and measured their cytotoxic effects.
View Article and Find Full Text PDFMammals maintain a nearly constant core body temperature (T) by balancing heat production and heat dissipation. This comes at a high metabolic cost that is sustainable if adequate calorie intake is maintained. When nutrients are scarce or experimentally reduced such as during calorie restriction (CR), endotherms can reduce energy expenditure by lowering T [1-6].
View Article and Find Full Text PDFBackground: Adolescence is a critical period for neural development, and alcohol exposure during adolescence can lead to an elevated risk for health consequences as well as alcohol use disorders. Clinical and experimental data suggest that chronic alcohol exposure may produce immunomodulatory effects that can lead to the activation of pro-inflammatory cytokine pathways as well as microglial markers. The present study evaluated, in brain and blood, the effects of adolescent alcohol exposure and withdrawal on microglia and on the most representative pro- and anti-inflammatory cytokines and major chemokines that can contribute to the establishing of a neuroinflammatory environment.
View Article and Find Full Text PDFCell-autonomous and cell-nonautonomous mechanisms of neurodegeneration appear to occur in the proteinopathies, including Alzheimer's and Parkinson's diseases. However, how neuronal toxicity is generated from misfolding-prone proteins secreted by nonneuronal tissues and whether modulating protein aggregate levels at distal locales affects the degeneration of postmitotic neurons remains unknown. We generated and characterized animal models of the transthyretin (TTR) amyloidoses that faithfully recapitulate cell-nonautonomous neuronal proteotoxicity by expressing human TTR in the muscle.
View Article and Find Full Text PDFBiochem Biophys Res Commun
November 2015
Nicotinamide N-methyltransferase (NNMT, E.C. 2.
View Article and Find Full Text PDFKikuchi-Fujimoto disease or histiocytic necrotizing lymphadenitis is a rare, benign condition, usually self-limited to a six-month period. Classic clinical presentation is characterized by cervical lymphadenopathy, leukopenia and prolonged fever. It affects principally young, Asiatic adult women, although a few cases in the pediatric population have been reported.
View Article and Find Full Text PDFBackground: Infections caused by community-associated strains of methicillin-resistant Staphylococcus aureus (CA-MRSA) are associated with a marked and prolonged host inflammatory response. In a sepsis simulation model, we tested whether the anesthetic ketamine inhibits the macrophage TNF response to antibiotic-exposed CA-MRSA bacteria via its antagonism of N-methyl-D-aspartate (NMDA) receptors. RAW264.
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