Mitochondrial respiration

Oligodendrocytes produce central nervous system myelin and provide metabolic support to axons. Myelin formation and repair are energetically expensive and oligodendrocyte metabolic defects have been postulated as a cause of neurodegeneration. Endocannabinoids modulate neuronal and astroglial metabolism and attenuate inflammatory demyelination in multiple sclerosis (MS) through the activation of CB1 receptors (CB1Rs). Myelinating oligodendrocytes and precursor cells (OPCs) express CB1Rs that mediate protection from excitotoxicity and promote lineage progression but the metabolic implications of

The goal of this work is to analyze the mitochondrial changes that Rotenone (Rot) treatment can induce in primary cortical neurons that could contribute to the schizophrenia-like phenotype animal model, previously demonstrated by our research group. For this, we previously determined the Rotenone (Rot) concentration in the cortex (1.325nM) from our animal model with a schizophrenia-like phenotype. Then, we treated the primary cortical neurons with Rot 1.325nM for 24h and investigated: the Rot cellular viability treatment by MTT and CytotoxGlo assay; CI enzymatic activity; oxygen consumption ra

A strong link between the SHANK3 gene mutations and autism spectrum disorder (ASD) has been established but its molecular mechanisms remain unknown. Here we hypothesize that a mutation in the Shank3 gene leads to alterations in the global proteome, and consequently, these alterations converge into cellular and behavioral deficits of ASD. To test this hypothesis, we comprehensively mapped the global proteome within the cortex of the Shank3Δ4-22 mice. Our preliminary results revealed a significant increase in one of the ATP synthase subunits (ATP-S) expression levels in the cortex of Shank3Δ4-22

Aims. Acute consumption of sweeteners has become increasingly common in modern diets. However, emerging research suggests that the impact of sweeteners on the hypothalamus, involved in regulating food intake [CA1] and metabolism, may be deleterious. Several studies have raised concerns about their potential effects on brain cellular metabolism (Kohno D et al.,2016), suggesting a mismatch between detection of false sugar and the energy value actually detected. This study aimed to investigate the dose-dependent impact of sweeteners on these energetic processes. Methods. Using the hypothalamic ce

Elevated NADPH-oxidase (NOX) activity, particularly NOX2, is implicated in the persistent pro-inflammatory phenotype observed in microglia following traumatic brain injury. NOX activation requires metabolic support, especially within the pentose-phosphate-pathway (PPP), to fulfil the heightened NADPH demand. Our objective was to identify key metabolic changes associated with NOX activation during pro-inflammatory stimulation in microglia. Using an immortalized microglia (IMG) cell line and PPP inhibitor, 6-aminonicotinamide (6-AN), we stimulated IMGs with LPS (100 ng/mL) and/or 6-AN for 24 hou

The neural control of sleep requires that sleep need is sensed during waking and discharged during sleep. While sleep loss has widespread consequences in the whole body and brain, perhaps the only realistic opportunity for separating causation from correlation exists in specialist neurons with active roles in sleep. To obtain an unbiased view of molecular changes in the brain underlying these processes, we characterized the transcriptomes of single sleep-control cells isolated from rested and sleep-deprived flies. Transcripts upregulated after sleep deprivation, in sleep-control neurons projec

…must be transported across the inner mitochondrial membrane into the mitochondrial matrix, where it is oxidized to fuel mitochondrial respiration. Pyruvate import is performed by the mitochondrial pyruvate carrier (MPC), a hetero-oligomeric complex composed by interdependent subunits MPC1 and MPC2. Pathogenic variants in the MPC1 gene disrupt mitochondrial pyruvate uptake and oxidation and cause autosomal-recessive early-onset neurological dysfunction in humans. The present work describes the first pathogenic variant