Topic: mitochondrial membrane potential

An elevated consumption of cocaine (benzoylmethylecgonine), which causes anesthetic and stimulant effects on the central nervous system, may be associated with several neurodegenerative conditions affecting dopaminergic neurons, such as Parkinson's disease (PD). To investigate the impact of cocaine on cell viability and morphology, dopaminergic neurons from the substantia nigra (SN4741) were cultured. Analysis involved assessing cell death (LDH levels) and cell morphology (GIEMSA staining) after a 24-hour treatment period. Additionally, the effects on reactive oxygen species (ROS) generation (

Huntington's disease (HD) is an inherited, incurable neurodegenerative disease that primarily affects neurons in the striatum. In the present study, we successfully used an optimized cell model of HD [Kraskovskaya et al., 2023] to evaluate the effectiveness of the sigma 1 receptor agonist compound 3-PPP (N-n-propyl-3-(3-hydroxyphenyl)piperidine). We showed that striatal neurons obtained by direct reprogramming of dermal fibroblasts from HD patients (HD iSN) exhibit aggregates of mutant huntingtin, but the number of cells containing aggregates is less than 5% of the total. We also showed that t

Hypoxic injury in developing glial cells and their differential response can result in neurological deficits in neonates. This study attempts to understand the role of autophagy in developing premyelinating oligodendrocytes (pre-OL), mature-OL and astrocytes exposed to hypoxic injury. Human fetal neural stem cell-derived pre-OL, mature OL and astrocytes were exposed to hypoxia (0.2% oxygen) and normoxia (20% oxygen) for 48 hours followed by RNA-sequencing. Transcriptomic analysis revealed upregulation of autophagy in mature OL and astrocytes but not in pre-OL. MO3.13 (resembling pre-OL) and SV

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

Synthetic cannabinoids as potent recreational drugs disrupt the endocannabinoid system in the brain, leading to severe mental and behavioral consequences. Cumyl-PINACA or SGT-24 is a synthetic agonist designed to bind cannabinoid receptor 1 (CB1) with very high affinity, yet the molecular mechanisms underlying its central toxic effects are poorly understood.In this study, we investigated the response of rat cortical neurons and astrocytes to SGT-24 at nanomolar concentrations (0.1 - 1000 nM). The effects of SGT-24 were dose- and time-dependent, as well as cell-specific. In neurons, 10 nM SGT-2

The aim of this study was to address the urgent global need for an effective therapeutic strategy against acute stroke and perinatal asphyxia. A promising answer to limitations of currently existing therapies might be the newly designed Pathway Preferential Estrogen-1 (PaPE-1). Estrogen receptor-mediated signaling is pivotal for neuroprotection, and its impairment during hypoxia/ischemia may increase the risk of cerebral infarction. Our goal was to selectively activate non-nuclear estrogen receptors signaling, providing a wide therapeutic window and minimizing adverse hormonal effects associat

SINO is a newly described syndrome characterized by Spastic paraplegia, Intellectual Disability, Nystagmus and Obesity, caused by heterozygous mutations in the KIDINS220 gene. KIDINS220 (kinase D interacting substrate of 220kDa) is a multi-functional scaffold protein abundantly expressed across the nervous system that participates in neural cell survival, maturation and plasticity. In our work, we study the physiopathology of KIDINS220 mutations following three parallel approaches. (i) We examined the molecular effects of KIDINS220 mutations in HEK293T and primary neurons. Immunocytochemistry

Dynamic alterations in mitochondrial Ca2+ levels are recognized for their role in regulating both mitochondrial and cellular functions, as well as influencing energy metabolism (1). Recent studies reported that mitochondrial Na+/Ca2+ exchanger (NCLX) is regulated by PKA phosphorylation on its regulatory domain and PDE2 plays a crucial role as a physiological determinant in the PKA-mediated regulation of NCLX (2, 3). A major unsolved question is what links the cell membrane signaling to mitochondria NCLX regulation. Here, we fluorescently monitored [Ca2+]m efflux mediated by the NCLX in mice hi