epigenetic brain cognition

How pain and sensorimotor behavior interact has been the subject of research and debate for many decades. This article reviews theories bearing on pain-sensorimotor interactions and considers their strengths and limitations in the light of findings from experimental and clinical studies of pain-sensorimotor interactions in the spinal and craniofacial sensorimotor systems. A strength of recent theories is that they have incorporated concepts and features missing from earlier theories to account for the role of the sensory-discriminative, motivational-affective, and cognitive-evaluative dimensions of pain in pain-sensorimotor interactions...

The therapeutic potential of aerobic exercise in mitigating seizures and cognitive issues in temporal lobe epilepsy (TLE) is recognized, yet the underlying mechanisms are not well understood. Using a rodent TLE model induced by Kainic acid (KA), we investigated the impact of a single bout of exercise (i.e., acute) or 4 weeks of aerobic exercise (i.e., chronic). Blood was processed for epilepsy-associated serum markers, and DNA methylation (DNAme), and hippocampal area CA3 was assessed for gene expression levels for DNAme-associated enzymes...

Early life stress (ELS), characterized as abuse, neglect, and abandonment, can cause several adverse consequences in the lives of affected individuals. ELS experiences can affect an individual's development in variable ways, persisting in the long term and promoting lasting impacts, considering that early exposure to stressors can be biologically incorporated, as prolonged stimulation of stress response systems affects the development of the brain structure and other body systems, increasing the risk of diseases associated with stress and cognitive impairment...

Biological aging is the correlated decline of multi-organ system integrity central to the etiology of many age-related diseases. A novel epigenetic measure of biological aging, DunedinPACE, is associated with cognitive dysfunction, incident dementia, and mortality. Here, we tested for associations between DunedinPACE and structural MRI phenotypes in three datasets spanning midlife to advanced age: the Dunedin Study (age=45 years), the Framingham Heart Study Offspring Cohort (mean age=63 years), and the Alzheimer's Disease Neuroimaging Initiative (mean age=75 years)...

Maintaining good health is crucial, and exercise plays a vital role in achieving this goal. It offers a range of positive benefits for cognitive function, regardless of age. However, as our population ages and life expectancy increases, cognitive impairment has become a prevalent issue, often coexisting with age-related neurodegenerative conditions. This can result in devastating consequences such as memory loss, difficulty speaking, and confusion, greatly hindering one's ability to lead an ordinary life. In addition, the decrease in mental capacity has a significant effect on an individual's physical and emotional well-being, greatly reducing their overall level of contentment and causing a significant financial burden for communities...

Schizophrenia (SCZ) is an articulated psychiatric syndrome characterized by a combination of genetic, epigenetic, and environmental factors. Our intention is to present a pathogenetic model combining SCZ alterations and the main cellular actors of the blood-brain barrier (BBB): endothelial cells (ECs), pericytes, and astrocytes. The homeostasis of the BBB is preserved by the neurovascular unit which is constituted by ECs, astrocytes and microglia, neurons, and the extracellular matrix. The role of the BBB is strictly linked to its ability to preserve the biochemical integrity of brain parenchyma integrity...

Emotional abuse, defined as degrading, manipulative, or neglectful behaviors by caregivers, represents a common adverse experience for children and adolescents, often co-occurring with other maltreatment types. Exposure to emotional abuse significantly affects mental health across the lifespan and is particularly associated with elevated depression risk.This review examinesmechanisms, by which emotional abuse influences brain development and the neuroendocrine stress response system and discusses the roles of genetic vulnerability and epigenetic processes in contributing to an elevated mental health risk...

Alzheimer's disease (AD) remains a complex challenge characterized by cognitive decline and memory loss. Genetic variations have emerged as crucial players in the etiology of AD, enabling hope for a better understanding of the disease mechanisms; yet the specific mechanism of action for those genetic variants remain uncertain. Animal models with reminiscent disease pathology could uncover previously uncharacterized roles of these genes. Using CRISPR/Cas9 gene editing, we generated a knockout model for abca7, orthologous to human ABCA7 - an established AD-risk gene...

BACKGROUND: Alzheimer's disease (AD) is a degenerative neurological disorder. Recent studies have indicated that histone deacetylases (HDACs) are among the most prominent epigenetic therapy targets and that HDAC inhibitors have therapeutic effects on AD. Here, we identified sodium valproate (VPA), a pan-HDAC inhibitor, and WT161, a novel HDAC6 selective inhibitor, as potential therapeutic agents for AD. Underlying molecular mechanisms were investigated. METHODS: A cellular model, N2a-APPswe, was established via lentiviral infection, and the APPswe/PSEN1dE9 transgenic mouse model was employed in the study...

Nearly two-thirds of patients with Alzheimer's are women. Identifying therapeutics specific for women is critical to lowering their elevated risk for developing this major cause of adult dementia. Moreover, targeting epigenetic processes that regulate multiple cellular pathways is advantageous given Alzheimer's multifactorial nature. Histone acetylation is an epigenetic process heavily involved in memory consolidation. Its disruption is linked to Alzheimer's. Through our computational studies, we predicted that the investigational drug RG2833 (N-[6-(2-aminoanilino)-6-oxohexyl]-4-methylbenzamide) has repurposing potential for Alzheimer's...

AIM: Offspring of obese mothers are at high risk of developing metabolic syndrome and cognitive disabilities. Impaired metabolism has also been reported in the offspring of obese fathers. However, whether brain function can also be affected by paternal obesity has barely been examined. This study aimed to characterize the learning deficits resulting from paternal obesity versus those induced by maternal obesity and to identify the underlying mechanisms. METHODS: Founder control and obese female and male Wistar rats were mated to constitute three first-generation (F1) experimental groups: control mother/control father, obese mother/control father, and obese father/control mother...

Alzheimer's disease (AD) constitutes a multifactorial neurodegenerative pathology characterized by cognitive deterioration, personality alterations, and behavioral shifts. The ongoing brain impairment process poses significant challenges for therapeutic interventions due to activating multiple neurotoxic pathways. Current pharmacological interventions have shown limited efficacy and are associated with significant side effects. Approaches focusing on the early interference with disease pathways, before activation of broad neurotoxic processes, could be promising to slow down symptomatic progression of the disease...

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...