New insights into the molecular biology of Alzheimer's-like cerebral amyloidosis achieved through multi-omics approaches.

Background: One of the neuropathologic hallmarks of Alzheimer's disease (AD) is amyloid plaques composed of fibrillar amyloid beta (Aβ) that accumulate in the hippocampus and cerebral cortex. The identification of molecular changes and interactions associated with Aβ-dependent cerebral amyloidosis is a need in the field. We hypothesize that structured datasets linking proteins to differentially abundant metabolites may provide an indirect but effective means of elucidating the processes and functions in which these metabolites are involved.

Sex-specific dysregulation of the CXCL1/CXCR1 Axis following cocaine exposure: Translational evidence for a potential biomarker of abstinence.

Cocaine disrupts neurotransmitter systems and promotes neuroinflammation by activating microglia and altering cytokine signaling. The CXCL1/CXCR1 axis is an essential signaling pathway for microglial regulation, may exhibit sex-specific responses to cocaine. In this study, male and female Wistar rats were exposed to acute (5, 15, or 30 mg/kg) or repeated (15 mg/kg/day for two weeks) cocaine.

Alteration of IGF-1 bioavailability due to PAPPA2 deficiency leads to sex-specific metabolic disturbances.

Background: The growth hormone (GH)/insulin-like growth factor (IGF-1) axis determines optimal growth and affects metabolism and energy homeostasis. Pregnancy-associated plasma protein-A2 (PAPPA2) regulates bioactive IGF-1 availability and patients with PAPPA2 deficiency have impaired growth and glucose metabolism. This axis is altered in metabolic disturbances such as obesity and anorexia nervosa in a sex-specific manner, but the mechanisms involved are not completely understood.

Exploring Vascular Endothelial Growth Factor and Other Blood-Brain Barrier Biomarkers in Cognition of First-Episode Psychosis: An Observational Study.

Cognitive deficits are a core feature of early stages of schizophrenia. However, according to neurodevelopmental models, the extent to which chemokines and growth factors are involved in cognitive function remains debatable. We aimed to investigate whether homeostatic/inflammatory chemokines and growth factors are associated with cognitive impairment in patients with first-episode psychosis (FEP) in remission.

Distinct cardiac troponin alterations in patients with cocaine and alcohol use disorders during abstinence for cardiovascular risk assessment.

Cocaine use is a well-established cardiovascular risk factor, further enhanced by concurrent alcohol use. However, cardiovascular risk is poorly managed in individuals with cocaine use disorder (CUD). This observational, cross-sectional case-control study assessed cardiac troponins T (cTnT) and I (cTnI) as biomarkers of myocardial injury in patients with CUD and/or alcohol use disorder (AUD) during abstinence.

Omega-3 Fatty Acids Mitigate Long-Lasting Disruption of the Endocannabinoid System in the Adult Mouse Hippocampus Following Adolescent Binge Drinking.

Adolescent binge drinking has lasting behavioral consequences by disrupting the endocannabinoid system (ECS) and depleting brain omega-3. The natural accumulation of omega-3 fatty acids in cell membranes is crucial for maintaining the membrane structure, supporting interactions with the ECS, and restoring synaptic plasticity and cognition impaired by prenatal ethanol (EtOH) exposure. However, it remains unclear whether omega-3 supplementation can mitigate the long-term effects on the ECS, endocannabinoid-dependent synaptic plasticity, and cognition following adolescent binge drinking.

Gestational saccharin consumption disrupts gut-brain axis glucose homeostasis control in adolescent offspring rats in a sex-dependent manner.

Background: Certain events that occur in early life, such as changes in nutrition, can promote structural and functional modifications in brain development, projecting to either short, medium, and/or long terms, resulting in metabolic programming. These effects depend on the timing, intensity, and duration of exposure, and are proposed to be the cause or contribute to chronic adult disorders. Recent studies have proposed that artificial non-nutritive sweeteners (NNS), such as saccharin, can be included as one of these developmental disruptors.

"Maladaptive stress-coping behavior in CXCR1-deficient mice: Impact of adolescent stress and alcohol exposure on neuroimmune responses and inflammation".

The CXCL1/CXCR1 chemokine axis regulates synaptic pruning, plasticity, and stress-related behaviors, influencing resilience or vulnerability to psychiatric disorders. Adolescence, a critical period for neuroimmune development, increases susceptibility to stressors. This study investigated how adolescent restraint stress and alcohol exposure affect stress-coping behavior, neuroimmune signaling, and systemic inflammation in adult wild-type (WT) and CXCR1 knock-out (KO) mice.

Serum Myeloperoxidase Activity Is Associated with Hoehn-Yahr Staging and Striatal Dopamine-Transporter Binding in Parkinson's Disease.

Background: The blood concentration of myeloperoxidase (MPO) is related to the severity of many age-related inflammatory diseases. However, it is unknown whether enzyme activity in the blood provides information on the degree of functional disability of Parkinson's disease (PD), a multifactorial disease in which aging and inflammation play an important role.

Objective: The aim of the study was to discern the relationship between MPO activity in blood serum and the clinical characteristics of PD, assessed by disease rating scales and neuroimaging methods.

Oleoylethanolamide effects on stress-induced ethanol consumption: A lipid at the crossroads between stress, reward and neuroinflammation.

The endocannabinoid system is involved in multiple drug-related behaviors and the transient increase in endogenous cannabinoids and endocannabinoid-like molecules contributes to healthy adaptation to stress exposure. Oleoylethanolamide (OEA) belongs to the N-acylethanolamines and interacts with the endocannabinoid system. In this study, we investigated the effect of systemic OEA treatment (10 mg/kg), before or after social defeat (SD), on ethanol self-administration (SA).

Exploratory study on plasma Acylglycerol and Acylethanolamide dysregulation in substance use and attention-deficit/hyperactivity disorder: Implications for novel biomarkers in dual diagnosis.

Substance use disorder (SUD) is a major global public health challenge, frequently co-occurring with psychiatric conditions such as attention-deficit/hyperactivity disorder (ADHD). Endocannabinoid system (ECS) dysregulation has been implicated in both SUD and ADHD, but the interplay between these conditions remains poorly understood. This study investigates plasma concentrations of endocannabinoid-congeners in individuals with SUD, with and without comorbid ADHD, to identify potential biomarkers.

Region-Specific Impact of Repeated Synthetic Cannabinoid Exposure and Withdrawal on Endocannabinoid Signaling, Gliosis, and Inflammatory Markers in the Prefrontal Cortex and Hippocampus.

Synthetic cannabinoid use raises concerns about its neuroinflammatory effects, including molecular adaptations of the endocannabinoid system (ECS) in the brain. This study investigates the pharmacological effects of 14-day repeated intraperitoneal administration, as well as 14-day administration followed by a 7-day withdrawal period of two synthetic cannabinoids: WIN55,212-2 and HU-210. The study assessed gene expression and protein markers related to the ECS, gliosis, and inflammation in two brain regions critical for cognitive processes and memory-key components of addiction pathways-the prefrontal cortex (PFC) and the hippocampus of rats.

A Combined GLP-1/PPARa/CB1-Based Therapy to Restore the Central and Peripheral Metabolic Dysregulation Induced by a High-Fructose High-Fat Diet.

Obesity remains a major epidemic in developed countries, with a limited range of effective pharmacological treatments. The pharmacological modulation of PPARα, CB1, or GLP-1 receptor activity has demonstrated beneficial effects, including anti-obesity actions. In this study, we evaluated a novel amide derivative of oleic acid and tyrosol (Oleyl hydroxytyrosol ether, OLHHA), a PPARα agonist, and CB1 antagonist, in combination with the GLP-1 agonist liraglutide (LIG), as an effective multitarget therapy to improve both the peripheral and central alterations in an animal model of diet-induced obesity.

Blood levels of cytokines highlight the role of inflammation in Alzheimer's disease.

Inflammation and angiogenesis have been defined as potential mechanisms associated with clinical progression from a cognitively normal state to Alzheimer's disease (AD). In this observational case-control study, we aimed to determine plasma levels of cytokines as indicators of inflammation involved in cognitive decline. We measured 30 plasma proteins in 49 controls (CTL), 36 individuals with mild cognitive impairment (MCI) and 52 patients diagnosed with probable AD.

Sex-specific alterations in emotional behavior and neurotransmitter systems in LPA receptor-deficient mice.

Lysophosphatidic acid (LPA) and the endocannabinoid system (ECS) are critical lipid signaling pathways involved in emotional regulation and behavior. Despite their interconnected roles and shared metabolic pathways, the specific contributions of LPA signaling through the LPA receptor to stress-related disorders remain poorly understood. This study investigates the effects of LPA receptor deficiency on emotional behavior and neurotransmitter-related gene expression, with a focus on sex-specific differences, using maLPA-null mice of both sexes.

Impact of Omega-3 on Endocannabinoid System Expression and Function, Enhancing Cognition and Behavior in Male Mice.

: Omega-3 long-chain polyunsaturated fatty acids (PUFAs) support brain cell membrane integrity and help mitigate synaptic plasticity deficits. The endocannabinoid system (ECS) is integral to synaptic plasticity and regulates various brain functions. While PUFAs influence the ECS, the effects of omega-3 on the ECS, cognition, and behavior in a healthy brain remain unclear.

Therapeutic Efficacy of the Inositol D-Pinitol as a Multi-Faceted Disease Modifier in the 5×FAD Humanized Mouse Model of Alzheimer's Amyloidosis.

Background/objectives: Alzheimer's disease (AD), a leading cause of dementia, lacks effective long-term treatments. Current therapies offer temporary relief or fail to halt its progression and are often inaccessible due to cost. AD involves multiple pathological processes, including amyloid beta (Aβ) deposition, insulin resistance, tau protein hyperphosphorylation, and systemic inflammation accelerated by gut microbiota dysbiosis originating from a leaky gut.

Cafeteria Diet Abstinence Induces Depressive Behavior and Disrupts Endocannabinoid Signaling in Dopaminergic Areas: A Preclinical Study.

Background: Alterations of dopamine (DA) transmission in the brain reward system can be associated with an addictive-like state defined as food addiction (FA), common in obese individuals. Subjects affected by FA experience negative feelings when abstinent from their preferred diet and may develop mood disorders, including depression, sustained by alterations in brain DA pathways.

Objective: This study aims to investigate the impact of long-term abstinence from a palatable diet on depressive-like behavior in rats, exploring neurochemical alterations in monoamine and endocannabinoid signaling in DA-enriched brain regions, including ventral tegmental area, dorsolateral striatum, substantia nigra and medial prefrontal cortex.

Association of Hemispheric Asymmetry of Dopamine-Transporter Binding with Risk of Parkinsonian Depression.

Background: Depression is the most common psychiatric disorder diagnosed in patients with Parkinson's disease (PD). A direct role in PD depression for loss of dopaminergic terminals and dopamine-transporter (DAT) expression in the striatum is revealed by many studies.

Objectives: The objective was to discern the relationship between DAT neuroimaging and risk of depression in PD.

Region-Specific Gene Expression Changes Associated with Oleoylethanolamide-Induced Attenuation of Alcohol Self-Administration.

Oleoylethanolamide (OEA) is a lipid with anti-inflammatory activity that modulates multiple reward-related behaviors. Previous studies have shown that OEA treatment reduces alcohol self-administration (SA) while inhibiting alcohol-induced inflammatory signaling. Nevertheless, the specific mechanisms that OEA targets to achieve these effects have not been widely explored.

Pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in bipolar disorder: A systematic review.

Background: The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD.