Neuroinflammation and neurodegeneration in Huntington's disease: genetic hallmarks, role of metals and organophosphates.

Huntington's disease (HDs) is a fatal, autosomal dominant, and hereditary neurodegenerative disorder characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances. HD is well linked to mutation in the HTT gene, which leads to an abnormal expansion of trinucleotide CAG repeats, resulting in the production of the mHTT protein and responsible for abnormally long poly-Q tract. These abnormal proteins disrupt cellular processes, including neuroinflammation, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction, ultimately leading to selective neuronal loss in the brain.

Population pharmacokinetic model of tranexamic acid in patients who undergo cardiac surgery with cardiopulmonary bypass.

Purpose: Tranexamic acid (TXA) is widely used as an antifibrinolytic drug. However, studies to determine the optimal blood concentration of TXA have produced inconsistent results. During cardiac surgery, cardiopulmonary bypass (CPB) has serious effects on drug distribution, elimination, and plasma concentration.

Exploring pathological targets and advancing pharmacotherapy in autism spectrum disorder: Contributions of glial cells and heavy metals.

Autism spectrum disorder (ASD) is a globally recognized neurodevelopmental condition characterized by repetitive and restrictive behavior, persistent deficits in social interaction and communication, mental disturbances, etc., affecting approximately 1 in 100 children worldwide. A combination of genetic and environmental factors is involved in the etiopathogenesis of the disease, but specific biomarkers have not yet been identified.

Restorative properties of chronic lurasidone treatment on emotional dysfunction in rats exposed to chronic unavoidable stress: A role for medial prefrontal cortex - nucleus accumbens network.

Anhedonia, a transdiagnostic symptom prevalent in depressive and psychotic disorders, poses a significant challenge for pharmacological intervention due to its association with impaired motivation. Understanding how psychotropic drugs can modulate this pathological domain and elucidating the molecular mechanisms underlying such effects are crucial endeavors in psychiatric research. In this study, we aimed to investigate the pro-motivational properties of lurasidone in a rat (Sprague Dawley males) model of anhedonia and to unravel the interplay between lurasidone and the brain regions critical for reward processing.

Effects of chronic ethanol exposure on dorsal medial striatal neurons receiving convergent inputs from the orbitofrontal cortex and basolateral amygdala.

Alcohol use disorder is associated with altered function of cortical-amygdala-striatal circuits such as the orbitofrontal cortex (OFC), basolateral amygdala (BLA) and their connections to the dorsal medial striatum (DMS) shown to be involved in goal-directed actions. Using retrobead tracing, we previously reported enhanced excitability of DMS-projecting OFC neurons in mice following 3-to-7-day withdrawal from chronic intermittent ethanol (CIE) exposure. In the same animals, spiking of DMS-projecting BLA neurons was decreased at 3-days post-withdrawal followed by an increase in firing at 7- and 14-days.

CD38-mediated oxytocin signaling in paraventricular nucleus contributes to empathic pain.

Empathy plays a crucial role in social communication and the perception of affective states and behavioral processes. In this study, we observed that empathic interaction with a mouse experiencing pain resulted in decreased mechanical pain thresholds and anxiety-like behaviors in its bystander, though the underlying mechanisms remain unknown. We demonstrated that CD38 expression in the paraventricular nucleus (PVN) was upregulated during empathic pain, and the pain and emotions of CD38 knockout (CD38KO) mice as bystanders were not affected.

Postoperative evaluation of interleukin-8 and C1q/TNF-related protein-12 in patients undergoing coronary artery bypass graft surgery.

Objective: Coronary artery bypass graft surgery is one of the most frequently performed surgeries worldwide. Coronary artery bypass graft surgery induces an inflammatory response. Interleukin-8 is a pro-inflammatory cytokine that plays a role in the pathogenesis of cardiovascular diseases.

Redefining Ketamine Pharmacology for Antidepressant Action: Synergistic NMDA and Opioid Receptor Interactions?

Ketamine is a racemic compound and medication comprised of ()-ketamine and ()-ketamine enantiomers and its metabolites. It has been used for decades as a dissociative anesthetic, analgesic, and recreational drug. More recently, ketamine, its enantiomers, and its metabolites have been used or are being investigated for the treatment of refractory depression, as well as for comorbid disorders such as anxiety, obsessive-compulsive, and opioid use disorders.

Nose to brain strategy coupled to nano vesicular system for natural products delivery: Focus on synaptic plasticity in Alzheimer's disease.

A wide number of natural molecules demonstrated neuroprotective effects on synaptic plasticity defects induced by amyloid-β (Aβ) in and Alzheimer's disease (AD) models, suggesting a possible use in the treatment of this neurodegenerative disorder. However, several compounds, administered parenterally and orally, are unable to reach the brain due to the presence of the blood-brain barrier (BBB) which prevents the passage of external substances, such as proteins, peptides, or phytocompounds, representing a limit to the development of treatment for neurodegenerative diseases, such as AD. The combination of nano vesicular systems, as colloidal systems, and nose to brain (NtB) delivery depicts a new nanotechnological strategy to overtake this limit and to develop new treatment approaches for brain diseases, including the use of natural molecules in combination therapy for AD.

Berberine ameliorates seizure activity and cardiac dysfunction in pentylenetetrazol-kindling seizures in rats: Modulation of sigma1 receptor, Akt/eNOS signaling, and ferroptosis.

Seizures can lead to cardiac dysfunction. Multiple pathways contribute to this phenomenon, of which the chaperone sigma-1 receptor (S1R) signaling represents a promising nexus between the abnormalities seen in both epilepsy and ensuing cardiac complications. The study explored the potential of Berberine (BER), a promising S1R agonist, in treating epilepsy and associated cardiac abnormalities in a pentylenetetrazol (PTZ) kindling rat model of epilepsy.

The α-synuclein seed amplification assay: Interpreting a test of Parkinson's pathology.

The α-synuclein seed amplification assay (αSyn-SAA) sensitively detects Lewy pathology, the amyloid state of α-synuclein, in the cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD). The αSyn-SAA harnesses the physics of seeding, whereby a superconcentrated solution of recombinant α-synuclein lowers the thermodynamic threshold (nucleation barrier) for aggregated α-synuclein to act as a nucleation catalyst ("seed") to trigger the precipitation (nucleation) of monomeric α-synuclein into pathology. This laboratory setup increases the signal for identifying a catalyst if one is present in the tissue examined.

Female Syrian hamster analyses of bremelanotide, a US FDA approved drug for the treatment of female hypoactive sexual desire disorder.

Hypoactive sexual desire disorder (HSDD) is the most reported sexual dysfunction among premenopausal women worldwide. Bremelanotide, trade name Vyleesi, has been approved by the United States Food and Drug Administration to treat HSDD. However, despite approval, very little is known about its neurobiological mechanism of action.

The novel miR_146-Tfdp2 axis antagonizes METH induced neuron apoptosis and cell cycle abnormalities in tree shrew.

Methamphetamine (METH) is a synthetic drug with potent addictive, relapse, and neurotoxic properties. METH abuse contributes to severe damage to the central nervous system, potentially causing cognitive impairments, behavioral changes, and neurodegenerative diseases. METH-induced neuronal damage is closely related to apoptosis and cell cycle abnormalities, while gene expression regulator microRNAs (miRNAs) may play extensive roles in this progress, but the specific mechanisms remain unclear.

Oligogenic risk score for Gilles de la Tourette syndrome reveals a genetic continuum of tic disorders.

Gilles de la Tourette syndrome (GTS) and other tic disorders (TDs) have a substantial genetic component with their heritability estimated at between 60 and 80%. Here we propose an oligogenic risk score of TDs using whole-genome sequencing (WGS) data from a group of Polish GTS patients, their families, and control samples (n = 278). In this study, we first reviewed the literature to obtain a preliminary list of 84 GTS/TD candidate genes.

Multivariate patterns among multimodal neuroimaging and clinical, cognitive, and daily functioning characteristics in bipolar disorder.

Individuals with bipolar disorder (BD) show heterogeneity in clinical, cognitive, and daily functioning characteristics, which challenges accurate diagnostics and optimal treatment. A key goal is to identify brain-based biomarkers that inform patient stratification and serve as treatment targets. The objective of the present study was to apply a data-driven, multivariate approach to quantify the relationship between multimodal imaging features and behavioral phenotypes in BD.

Cannabinoid type-1 receptors in CaMKII neurons drive impulsivity in pathological eating behavior.

Objectives: Overconsumption of palatable food and energy accumulation are evolutionary mechanisms of survival when food is scarce. These innate mechanisms becom detrimental in obesogenic environment promoting obesity and related comorbidities, including mood disorders. This study aims at elucidating the role of the endocannabinoid system in energy accumulation and hedonic feeding.

Deficiency of histamine H receptors in parvalbumin-positive neurons leads to hyperactivity, impulsivity, and impaired attention.

Attention deficit hyperactivity disorder (ADHD), affecting 4% of the population, is characterized by inattention, hyperactivity, and impulsivity; however, its neurophysiological mechanisms remain unclear. Here, we discovered that deficiency of histamine H receptor (HR) in parvalbumin-positive neurons in substantia nigra pars recticulata (PV) attenuates PV neuronal activity and induces hyperactivity, impulsivity, and inattention in mice. Moreover, decreased HR expression was observed in PV in patients with ADHD symptoms and dopamine-transporter-deficient mice, whose behavioral phenotypes were alleviated by HR agonist treatment.

Therapeutic Potential of Agmatine in Essential Tremor Through Regulation of Lingo-1 and Inflammatory Pathways.

Purpose: Essential tremor (ET) is a prevalent movement disorder, yet current therapeutic options remain limited. Emerging evidence implicates leucine-rich repeat and immunoglobulin-like domain-containing protein (Lingo-1) and neuroinflammation in the pathophysiology of ET. This study aimed to investigate whether agmatine, a biogenic amine neuromodulator attenuates tremors and modulates the expression of Lingo-1 and proinflammatory markers in a rodent model of ET.

CBD and the 5-HT1A receptor: A medicinal and pharmacological review.

Cannabidiol (CBD), a phytocannabinoid, has emerged as a promising candidate for addressing a wide array of symptoms. It has the ability to bind to multiple proteins and receptors, including 5-HT1AR, transient receptor potential vanilloid 1 (TRPV1), and cannabinoid receptors. However, CBD's pharmacodynamic interaction with 5-HT1AR and its medicinal outcomes are still debated.

The effects of social loss and isolation on partner odor investigation and dopamine and oxytocin receptor expression in female prairie voles.

In humans, grief is characterized by intense sadness, intrusive thoughts of the deceased, and intense longing for reunion with the deceased. Human fMRI studies show hyperactivity in emotional pain and motivational centers of the brain when an individual is reminded of a deceased attachment figure, but the molecular underpinnings of these changes in activity are unknown. Prairie voles (Microtus ochrogaster), which establish lifelong social bonds between breeding pairs, also display distress and motivational shifts during periods of prolonged social loss, providing a model to investigate these behavioral and molecular changes at a mechanistic level.

Multigenerational Consequences of Prenatal Exposure to Benzophenone-3 Demonstrate Sex- and Region-Dependent Neurotoxic and Pro-Apoptotic Effects in Mouse Brain.

Benzophenone-3 (BP-3), commonly used as a UV filter in personal care products and as a stabilizer, is an alleged endocrine disruptor with potential neurodevelopmental impacts. Despite its abundance in the environment, the studies on its effect on brain development are scarce, especially in terms of multigenerational impact. In this work, for the first time, we examined neurotoxic and pro-apoptotic effects of BP-3 on mouse brain regions (cerebral cortex and hippocampus) in both the first (F) and second (F) generations after maternal exposure to environmentally relevant BP-3 levels.

New High-Affinity Peptide Ligands for Kv1.2 Channel: Selective Blockers and Fluorescent Probes.

Advanced molecular probes are required to study the functional activity of the Kv1.2 potassium channel in normal and pathological conditions. To address this, a fully active Kv1.

Galantamine-Memantine Combination in the Treatment of Parkinson's Disease Dementia.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects over 1% of population over age 60. It is defined by motor and nonmotor symptoms including a spectrum of cognitive impairments known as Parkinson's disease dementia (PDD). Currently, the only US Food and Drug Administration-approved treatment for PDD is rivastigmine, which inhibits acetylcholinesterase and butyrylcholinesterase increasing the level of acetylcholine in the brain.

Assessing three novel composite anthropometric-metabolic indices for predicting 10-year incidence of metabolic syndrome: findings from the kerman coronary artery disease risk factors study (KERCADRS).

Purpose: Metabolic syndrome (MetS) is a condition of high prevalence worldwide associated with increased risk of cardiovascular disease. The predictive value of novel indices of combined anthropometric and serum lipid parameters as predictors of MetS is, to our knowledge, unexplored. We aimed to assess the 10-year predictive value of three indices of triglyceride-glucose index (TyG), visceral adiposity index (VAI), and lipid accumulation product (LAP) for incidence of MetS in Southeastern Iran.