epigenetic brain cognition

BACKGROUND: Genetic and environmental factors contribute to the pathogenesis of schizophrenia (SZ) and bipolar disorder (BD). Among genetic risk groups stratified by combinations of Polygenic Risk Score (PRS) deciles for SZ, BD and SZ versus BD, genetic SZ risk groups had high SZ risk and prominent cognitive impairments. Furthermore, epigenetic alterations are implicated in these disorders. However, it was unclear whether DNA Methylation Risk Scores (MRSs) for SZ risk derived from blood and brain tissues were associated with SZ risk, particularly the PRS-stratified genetic SZ risk group...

Mitochondrial metabolism can contribute to nuclear histone acetylation among other epigenetic mechanisms. A central aspect of this signaling pathway is acetyl-L-carnitine (LAC), a pivotal mitochondrial metabolite best known for its role in fatty acid oxidation. Work from our and other groups suggested LAC as a novel epigenetic modulator of brain plasticity and a therapeutic target for clinical phenotypes of depression linked to childhood trauma. Aberrant mitochondrial metabolism of LAC has also been implicated in the pathophysiology of Alzheimer's disease...

Alzheimer's Disease (AD) is a disorder characterized by cognitive decline, neurodegeneration, and accumulation of amyloid plaques and tau neurofibrillary tangles in the brain. Dysregulation of epigenetic histone modifications may lead to expression of transcriptional programs that play a role either in protecting against disease genesis or in worsening of disease pathology. One such histone modification, acetylation of histone H3 lysine residue 27 (H3K27ac), is primarily localized to genomic enhancer regions and promotes active gene transcription...

Epilepsy is a common neurological disorder characterized by recurrent seizures with excessive and abnormal neuronal discharges. Epileptogenesis is usually involved in neuropathological processes such as ion channel dysfunction, neuronal injury, inflammatory response, synaptic plasticity, gliocyte proliferation and mossy fiber sprouting, currently the pathogenesis of epilepsy is not yet completely understood. A growing body of studies have shown that epigenetic regulation, such as histone modifications, DNA methylation, noncoding RNAs (ncRNAs), N6-methyladenosine (m6A) and restrictive element-1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) are also involved in epilepsy...

Chronic stress (CS) can have long-lasting consequences on behavior and cognition, that are associated with stable changes in gene expression in the brain. Recent work has examined the role of the epigenome in the effects of CS on the brain. This review summarizes experimental evidence in rodents showing that CS can alter the epigenome and the expression of epigenetic modifiers in brain cells, and critically assesses their functional effect on genome function. It discusses the influence of the developmental time of stress exposure on the type of epigenetic changes, and proposes new lines of research that can help clarify these changes and their causal involvement in the impact of CS...

Epigenetic mechanisms play a primary role in the cellular damage associated with brain aging. Histone posttranslational modifications represent intrinsic molecular alterations essential for proper physiological functioning, while divergent expression and activity have been detected in several aspects of brain aging. Aberrant histone methylation has been involved in neural stem cell (NSC) quiescence, microglial deficits, inflammatory processes, memory impairment, cognitive decline, neurodegenerative diseases, and schizophrenia...

Gene fusion events have been linked to oncogenesis in many cancers. However, gene fusions in meningioma are understudied compared to somatic mutations, chromosomal gains/losses, and epigenetic changes. Fusions involving B-raf proto-oncogene, serine/threonine kinase (BRAF) are subtypes of oncogenic BRAF genetic abnormalities that have been reported in certain cases of brain tumors, such as pilocytic astrocytomas. However, BRAF fusions have not been recognized in meningioma. We present the case of an adult female presenting with episodic partial seizures characterized by déjà vu, confusion, and cognitive changes...

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In the past few decades, breakthrough progress has been made in the gut liver brain axis, mainly through understanding its formation mechanism and increasing treatment strategies. In this review, we discuss various complex networks including barrier permeability, gut hormones, gut microbial metabolites, vagus nerve, neurotransmitters, immunity, brain toxic metabolites, β-amyloid (Aβ) metabolism, and epigenetic regulation in the gut-liver-brain axis...

The repressor element-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is an epigenetic master regulator that plays a crucial role during nervous system development and maturation. REST function was originally described during development, where it determines neuronal phenotype. However, recent studies showed that REST participates in several processes in the adult brain, including neuronal plasticity and epileptogenesis. In this regard, the relationships between REST and epilepsy are still controversial and need further investigation...

Prenatal stress is increasingly recognized as a significant factor impacting an individual's life from the beginning. This comprehensive review explores the intricate relationship between prenatal stress and its effects on behaviour, cognition, and psychopathology. Key findings reveal that prenatal stress can lead to a wide range of adverse outcomes in offspring, including neurodevelopmental disorders, emotional dysregulation, cognitive deficits, mood disorders, and an increased risk of psychopathological conditions...

Multiple sclerosis (MS) is a primary inflammatory demyelinating disease with different clinical courses and subtypes. The present study aimed to determine whether mitochondrial dysfunction and sirtuins 1 and 3, as metabolism and epigenetic modifying factors, might contribute to MS disease progression measured by physical disability and cognitive impairment.The volunteers (n = 20 controls, n = 59 MS) were recruited and assessed for cognitive function and disability scores; then, patients were clinically classified as relapsing-remitting (RR) in remission phase, RR in relapse phase, and secondary progressive MS...

Nicotinamide riboside (NR) increases blood levels of NAD+, a cofactor central to energy metabolism, and improves brain function in some rodent models of neurodegeneration. We conducted a placebo-controlled randomized pilot study with the primary objective of determining safety of NR in older adults with mild cognitive impairment (MCI). Twenty subjects with MCI were randomized to receive placebo or NR using dose escalation to achieve, and maintain, a final dose of 1 g/day over a 10-week study duration. The primary outcome was post-treatment change from baseline measures of cognition (Montreal Cognitive Assessment, MoCA)...

Aluminum is a common environmental neurotoxin. Aluminum ions can cross the blood-brain barrier and accumulate in different brain regions, damage brain tissue, and cause cognitive impairment, but the molecular mechanism of aluminum neurotoxicity is not precise. This study investigated the effects of miR-204-5p, target gene EphB2, and downstream signaling pathway NMDAR-ERK-CREB-Arc on cognitive dysfunction induced by aluminum exposure. The results showed that the learning and memory of the rats were impaired in behavior...

Aluminum (Al) is a low toxic trace element that can accumulate in the nervous system and induce cognitive disorders characterized by reduced learning and memory ability. Neuroepigenetic effects are structural changes in cellular function by the brain in response to environmental stimuli by altering the expression of specific genes and repressing normal cellular transcription, leading to abnormalities in a variety of biological processes within the nervous system and affecting neurobehavioral responses. One of the most important mechanisms of epigenetic control on chromatin shape is histone modification...

Traumatic stress is associated with both accelerated epigenetic age and increased risk for dementia. Accelerated epigenetic age might link symptoms of traumatic stress to dementia-associated biomarkers, such as amyloid-beta (Aβ) proteins, neurofilament light (NFL), and inflammatory molecules. We tested this hypothesis using longitudinal data obtained from 214 trauma-exposed military veterans (85 % male, mean age at baseline: 53 years, 75 % White) who were assessed twice over the course of an average of 5...

As aging societies in the western world face a growing prevalence of vascular cognitive impairment and Alzheimer's disease (AD), understanding their underlying causes and associated risk factors becomes increasingly critical. A salient concern in the western dietary context is the high consumption of methionine-rich foods such as red meat. The present review delves into the impact of this methionine-heavy diet and the resultant hyperhomocysteinemia on accelerated cerebrovascular and brain aging, emphasizing their potential roles in cognitive impairment...

Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) plays a vital role in a large number of neuronal processes underlying learning and memory, which are known to be disrupted in schizophrenia. However, Lingo-1 has never been examined in the context of schizophrenia. The genetic association of a single-nucleotide polymorphism (SNP, rs3144) and methylation (CpG sites) in the Lingo-1 3'-UTR region was examined, with the testing of cognitive dysfunction and white matter (WM) integrity in a schizophrenia case-control cohort (n = 268/group)...

HIV-associated neurocognitive disorders (HAND) is a term describing a complex set of cognitive impairments accompanying HIV infection. Successful antiretroviral therapy (ART) reduces the most severe forms of HAND, but milder forms affect over 50% of people living with HIV (PLWH). Pathogenesis of HAND in the ART era remains unknown. A variety of pathogenic factors, such as persistent HIV replication in the brain reservoir, HIV proteins released from infected brain cells, HIV-induced neuroinflammation, and some components of ART, have been implicated in driving HAND pathogenesis in ART-treated individuals...

Non-familial Alzheimer's disease (AD) occurring before 65 years of age is commonly referred to as early-onset Alzheimer's disease (EOAD) and constitutes ~ 5-6% of all AD cases (Mendez et al. in Continuum 25:34-51, 2019). While EOAD exhibits the same clinicopathological changes such as amyloid plaques, neurofibrillary tangles (NFTs), brain atrophy, and cognitive decline (Sirkis et al. in Mol Psychiatry 27:2674-88, 2022; Caldwell et al. in Mol Brain 15:83, 2022) as observed in the more prevalent late-onset AD (LOAD), EOAD patients tend to have more severe cognitive deficits, including visuospatial, language, and executive dysfunction (Sirkis et al...

BACKGROUND: Arsenic is present in above permissible safe limits in groundwater, soil, and food, in various areas of the world. This is increasing exposure to humankind and affecting health in various ways. Alternation in cognition is one among them. Epidemiological research has reflected the impact of arsenic exposure on children in the form of diminished cognition. AIMS: Considering this fact, the present study reviewed the impact of arsenic on amyloid precursor protein, which is known to cause one of the commonest cognitive disorders such as Alzheimer's disease...