Apoptosis

Accumulation of heavy metals (Mn and Ni) and prolonged exposure to stress are associated with adverse health outcomes. Various studies have elucidated individually the impacts of stress and metal exposures on brain constituents and function. However, no study has examined the effects of co-exposure to stress, Mn, and Ni in the brain. This study addresses this gap by evaluating oxidative and glial responses, apoptotic activity, as well as cognitive processes in a rat model. Adult Wistar rats were exposed to vehicle (control), restraint stress, 25mg/kg of manganese (Mn) or nickel (Ni), and combi

Proper interneuron migration and distribution are essential for optimal brain function. Disruptions of this process can impair the excitation/inhibition balance, leading to neurodevelopmental disorders. As such, ionizing radiation poses a particular risk to the developing brain, as it can lead to excessive fetal DNA damage and subsequent microcephaly. Although research on radiation-induced microcephaly has mainly focused on glutamatergic excitatory neurons, the impact on GABAergic interneurons is equally crucial. Understanding potential disruptions is essential for comprehensive insights into

…We find that CRs apoptosis plays a crucial role in facilitating the proper development of inhibitory connectivity from

Vitamin D deficiency (VDD) is a worldwide problem, especially among the elderly and epidemiological studies have found a link between VDD, cognitive decline and depression. However, it is unclear whether VDD directly drives the development of depression and cognitive decline or whether it is secondary to co-occurring pathology.In this study, we sought to determine whether long-term VDD causes memory impairments and depressive-like behavior alone or in combination with chronic stress and to elucidate co-occurring dysfunctions in neuronal and glial plasticity in the dentate gyrus (DG) of the hip

We aimed to investigate the effect of taurine especially on apoptosis and also inflammatory and oxidative processes in an Alzheimer-like disease model induced by intracerebroventricular(icv) Amyloid Beta 1-42(Aβ1-42) injection.30 Wistar Albino rats were divided into 4 groups: Control(n:7), Taurine(n:7), icv Aβ1-42(n:8), icv Aβ1-42+taurine(n:8). After administration of icv Aβ1-42 to the relevant groups, taurine groups received taurine by oral gavage at 250 mg/kg/day for 32 days. Rats were sacrificed on day 33. Analysis were performed on rat brain tissue. To evaluate the apoptosis bax, bcl-2, cl

E2F4 is a transcription factor with a prominent role in cell homeostasis. We have shown that a mutant form of mouse E2F4 (E2F4DN), carrying T249A/T251A mutations, is a multifactorial therapeutic agent against Alzheimer’s disease (AD). Our current hypothesis for the mechanism of action of E2F4DN is that the phosphorylation of the Thr249/Thr251 motif by the stress kinase p38MAPK prevents the homeostatic function of E2F4, while E2F4DN restores it. To test this hypothesis, we have focused on N2a neuroblastoma-derived neurons treated with camptothecin (CPT) to induce DNA damage, as a mechanism of c

Apoptosis, a programmed, non-inflammatory type of cell death, is a key homeostatic mechanism in all organisms. In the nervous system of rodents, pronounced apoptotic neuronal loss takes place during the first days of life, and early neuronal activity is one of the essential factors regulating this process.The project aimed to investigate the effects of local neuronal silencing on postnatal apoptosis and cortical activity. New-born mice were implanted with drug-loaded polymers to achieve local and chronic neuronal inactivation in the somatosensory cortex. Subsequent combination of in vivo elect

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

Omentin-1 (OMNT1), is adipokine involved in regulation of energy metabolism, insulin sensitivity, and reproduction. Our previous study documented expression and in vitro effect of OMNT1 on endocrine function of porcine anterior pituitary cells. However, its role in hypothalamus remains unknown. The present study examines expression and impact of OMNT1 on the mouse hypothalamic neuronal GT1-7 cells (in vitro model of GnRH-secreting neurons). The mRNA expression of OMNT1 and its potential receptor, insulin receptor, as well as co-localization of OMNT1 with GnRH, were determined using RT-qPCR and

The melanocortin receptor subtype 4 (MC4R) is expressed in various human cells such as skin melanocytes, astrocytes, and neural progenitor cells1.Our aim is to evaluate the role of MCR4 as a novel target in melanoma therapy, using a selective antagonist ML00253764 (ML) alone and in combination with the B-Raf V600E inhibitor Vemurafenib.We employed the human melanoma B-Raf mutated A-2058 and WM 266-4 cell lines, while the CRISPR/Cas9 system was used to eliminate the MCR4 gene in the A-2058 cell line (MCR4 null).MC4R protein expression in melanoma cells was then tested though immunohistochemistr

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

…been shown that oxidative stress and apoptosis play a major role in the pathology of PD. One of the most commonly used models for in vitro investigation of PD is the SH-SY5Y neuroblastoma cell line and application of hydroxydopamine (6-OHDA). The 6-OHDA exerts its cytotoxicity by generating reactive oxygen species (ROS) such as hydrogen peroxide, superoxide anion and hydroxyl-radical, leading to oxidative stress by disrupting the mitochondrial membrane integrity,

…involved in tumor cell invasion, apoptosis, and resistance to chemotherapy. GBM presents major challenges due to its rapid progression and resistance to conventional treatments. Using immunocytochemistry, CD9 is used as a marker to identify distinct cell populations within GBM cultures. Simultaneously, the study investigates CD9 expression patterns by flow cytometry, providing valuable insights into its pot

…degeneration and cell death by apoptosis. Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), along with brain-derived neurotrophic factor (BDNF) are involved in neuroprotection. Levels of both DHEA(S) and BDNF d

…Apoptosis and autophagy are critical cell death signaling pathways after SCI that should be targeted for early therapeutic interventions to mitigate their adverse effects and promote functional recovery. Tibolone (TIB) is a selective tissue estrogen activity regulator (STEAR) with neuroprotective properties demonstrate

Opioids use cause thousands of deaths per year in United States. Lately, several studies have been focused on ibogaine (IBO), a psychoactive alkaloid with the ability to treat drug dependence and reduce withdrawal syndrome. The mechanism by which IBO exerts its anti-addictive effects is unknown. This study aims to identify changes in the gene expression after a single oral dose of IBO in different brain areas. Male and female C57BL/6 mice were treated with 60 mg/kg of IBO by gavage. Four hours post-administration frontal cortex samples of three males and three females were obtained to perform

Microcephaly is a disease in which the head circumference and brain volume decrease. Patients with microcephaly show a range of cognitive deficits. One of the causes of microcephaly is mutations in the RTTN gene. RTTN mutations are responsible for syndromic malformations of cortical development. Here we have generated on-chip human brain organoids and 3D-hippocampal organoids to study the role of RTTN in the developing human brain.A RTTN homozygous pathogenic mutation was introduced in human embryonic stem cells using CRISPR/Cas9 genome editing. The developing control on-chip brain organoids e

The capacities to learn and to store memories are two of the most important functions of the brain, but these abilities are inherently at odds with each other. On one hand, a neuronal network must be flexible enough to quickly store new information, but on the other it must be stable enough to prevent old memories from being constantly overwritten. Metaplasticity in which the timescale of synaptic modifications made by an individual neuron changes could resolve this flexibility-stability tradeoff. We propose that this strategy may be implemented in the olfactory bulb (OB). A striking, characte

Epithelial cell sheets form a fundamental role in the developing embryo, and also in adult tissues including the gut and the cornea of the eye. Soft and active matter provides a theoretical and computational framework to understand the mechanics and dynamics of these tissues.I will start by introducing the simplest useful class of models, active brownian particles (ABPs), which incorporate uncoordinated active crawling over a substrate and mechanical interactions. Using this model, I will show how the extended ’swirly’ velocity fluctuations seen in sheets on a substrate can be understood using