Lifelong exposure to n-3 PUFA deficiency leads to anxiety-like profile in male and female adolescent rats: Impact on spleen-brain axis.

Low consumption of n-3 polyunsaturated fatty acids (PUFA) during the developmental period has been increasingly associated with an increased risk of depressive-like symptoms in both male and female sexes. Therefore, here we performed behavioral and biochemical quantifications in adolescent rats to evaluate possible sex-driven differences in the development of anxiety-like disorders related to life-long n-3 PUFA low intake. Male and female adolescent rats fed for their entire life with n-3 PUFA poor diet showed an anxiety-like profile compared to n6/n-3 PUFA balanced diet.

Sex differences in the BTBR idiopathic mouse model of autism spectrum disorders: Behavioural and redox-related hippocampal alterations.

Autism spectrum disorders (ASD) are highly heterogeneous neurodevelopmental diseases. Epidemiological data report that males have been diagnosed with autism more frequently than females. However, recent studies hypothesize that females' low incidence might be underestimated due to standard clinical measures of ASD behavioural symptoms, mostly derived from males.

Amygdalar neurotransmission alterations in the BTBR mice model of idiopathic autism.

Autism Spectrum Disorders (ASD) are principally diagnosed by three core behavioural symptoms, such as stereotyped repertoire, communication impairments and social dysfunctions. This complex pathology has been linked to abnormalities of corticostriatal and limbic circuits. Despite experimental efforts in elucidating the molecular mechanisms behind these abnormalities, a clear etiopathogenic hypothesis is still lacking.

Analysis of Adherence to anti-PCSK9 Antibody Therapy among Patients from Italy.

Introduction: Hypercholesterolemia is one of the main risk factors associated with atherosclerotic cardiovascular disease and coronary heart disease. Statins are the standard cholesterollowering treatment; however, they have shown, in clinical practice, a reduced adherence to therapy (<50%) and a modest achievement of the expected outcomes for treatment. This condition prompt scientific research to develop drugs with different mechanisms of action.

Social isolation from early life induces anxiety-like behaviors in adult rats: Relation to neuroendocrine and neurochemical dysfunctions.

Subjects suffering from psychosis frequently experience anxiety. However, mechanisms underlying this comorbidity remain still unclear. We investigated whether neurochemical and neuroendocrine dysfunctions were involved in the development of anxiety-like behavior in a rodent model of psychotic-like symptoms, obtained by exposing male rats to social isolation rearing from postnatal day 21 to postnatal day 70.

Glucoraphanin Triggers Rapid Antidepressant Responses in a Rat Model of Beta Amyloid-Induced Depressive-like Behaviour.

Glucoraphanin (GRA) is a natural compound that has shown beneficial effects in chronic diseases and in central nervous system disorders. Moreover, GRA displayed antidepressant activity in preclinical models. We have previously demonstrated that a single intracerebroventricular administration of soluble amyloid-beta 1-42 (sAβ 1-42) in rat evokes a depressive-like phenotype by increasing immobility frequency in the forced swimming test (FST).

Ketamine administration in early postnatal life as a tool for mimicking Autism Spectrum Disorders core symptoms.

Autism Spectrum Disorders (ASD) core symptoms include deficits of social interaction, stereotyped behaviours, dysfunction in language and communication. Beyond them, several additional symptoms, such as cognitive impairment, anxiety-like states and hyperactivity are often occurring, mainly overlapping with other neuropsychiatric diseases. To untangle mechanisms underlying ASD etiology, and to identify possible pharmacological approaches, different factors, such as environmental, immunological and genetic ones, need to be considered.

SARS-CoV-2 Gamma and Delta Variants of Concern Might Undermine Neutralizing Activity Generated in Response to BNT162b2 mRNA Vaccination.

The Delta variant raised concern regarding its ability to evade SARS-CoV-2 vaccines. We evaluated a serum neutralizing response of 172 Italian healthcare workers, three months after complete Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer) vaccination, testing their sera against viral isolates of Alpha, Gamma and Delta variants, including 36 subjects with a previous SARS-CoV-2 infection. We assessed whether IgG anti-spike TRIM levels and serum neutralizing activity by seroneutralization assay were associated.

Palmitoylethanolamide dampens neuroinflammation and anxiety-like behavior in obese mice.

High-fat diet (HFD) consumption leads to obesity and a chronic state of low-grade inflammation, named metainflammation. Notably, metainflammation contributes to neuroinflammation due to the increased levels of circulating free fatty acids and cytokines. It indicates a strict interplay between peripheral and central counterparts in the pathogenic mechanisms of obesity-related mood disorders.

Precision Medicine in Alzheimer's Disease: Investigating Comorbid Common Biological Substrates in the Rat Model of Amyloid Beta-Induced Toxicity.

Alzheimer's disease (AD), one of the most widespread neurodegenerative disorder, is a fatal global burden for the elder population. Although many efforts have been made, the search of a curative therapy is still ongoing. Individuating phenotypic traits that might help in investigating treatment response is of growing interest in AD research.

Sex-tailored pharmacology and COVID-19: Next steps towards appropriateness and health equity.

Making gender bias visible allows to fill the gaps in knowledge and understand health records and risks of women and men. The coronavirus disease 2019 (COVID-19) pandemic has shown a clear gender difference in health outcomes. The more severe symptoms and higher mortality in men as compared to women are likely due to sex and age differences in immune responses.

The Therapeutic Potential of Celastrol in Central Nervous System Disorders: Highlights from In Vitro and In Vivo Approaches.

Celastrol, the most abundant compound derived from the root of largely used in traditional Chinese medicine, has shown preclinical and clinical efficacy for a broad range of disorders, acting via numerous mechanisms, including the induction of the expression of several neuroprotective factors, the inhibition of cellular apoptosis, and the decrease of reactive oxygen species (ROS). Given the crucial implication of these pathways in the pathogenesis of Central Nervous System disorders, both in vitro and in vivo studies have focused their attention on the possible use of this compound in these diseases. However, although most of the available studies have reported significant neuroprotective effects of celastrol in cellular and animal models of these pathological conditions, some of these data could not be replicated.

Sublingual AKBA Exerts Antidepressant Effects in the Aβ-Treated Mouse Model.

The 3-O-acetyl-11-keto-β-boswellic acid (AKBA) is the most active compound of proposed for treating neurodegenerative disorders, including Alzheimer's disease (AD), characterized in its early phase by alteration in mood. Accordingly, we have previously demonstrated that an intracerebroventricular injection of soluble amyloid beta (Aβ) peptide evokes a depressive-like phenotype in rats. We tested the protective effects of AKBA in the mouse model of an Aβ-induced depressive-like phenotype.

N-3 PUFA Prevent Oxidative Stress in a Rat Model of Beta-Amyloid-Induced Toxicity.

Polyunsaturated fatty acids (PUFA) are involved in brain disorders associated to amyloid beta (Aβ) toxicity for which oxidative stress, neurochemical dysfunctions, and neuroinflammation are underlying mechanisms. Here, mechanisms through which lifelong exposure to n-3 PUFA-enriched or n-6/n-3 balanced diets could elicit a protective role in a rat model of Aβ-induced toxicity were investigated. To this aim, we quantified hippocampal reactive oxygen species (ROS) amount, 8-hydroxy-2'-deoxyguanosine and interleukin-10 levels, NADPH oxidase (NOX) 1, NOX2, superoxide dismutase 1, and glutathione contents, as well as plasmatic malondialdehyde.

Postnatal Antioxidant and Anti-inflammatory Treatments Prevent Early Ketamine-Induced Cortical Dysfunctions in Adult Mice.

Early brain insult, interfering with its maturation, may result in psychotic-like disturbances in adult life. Redox dysfunctions and neuroinflammation contribute to long-term psychiatric consequences due to neurodevelopmental abnormalities. Here, we investigated the effects of early pharmacological modulation of the redox and inflammatory states, through celastrol, and indomethacin administration, on reactive oxygen species (ROS) amount, levels of malondialdehyde (MDA) and antioxidant enzymes (superoxide dismutase 1, SOD1, glutathione, GSH, and catalase, CAT), as well as of pro-inflammatory cytokines (tumor necrosis factor-alpha, TNF-α, interleukin-6, IL-6, and interleukin-1 beta, IL-1β), in the prefrontal cortex of adult mice exposed to a neurotoxic insult, i.

Palmitoylethanolamide counteracts brain fog improving depressive-like behaviour in obese mice: Possible role of synaptic plasticity and neurogenesis.

Background And Purpose: High-fat diet (HFD)-induced obesity is accompanied by metabolic and neurochemical changes that have been associated with depression. Recent studies indicate that palmitoylethanolamide (PEA) exerts metabolic effects and holds neuroprotective potential. However, studies on HFD exposure in mice which investigate the effects of PEA on monoamine system and synaptic plasticity are limited.

Depressive-like phenotype evoked by lifelong nutritional omega-3 deficiency in female rats: Crosstalk among kynurenine, Toll-like receptors and amyloid beta oligomers.

Depression is one of the most common psychiatric diseases and the prevalence of depressive symptoms in women is almost twice compared to men, although the reasons of this gender difference are not fully understood yet. Recently, soluble amyloid beta (Aβ) peptide has been receiving great importance in the development of depression, also considering that depression is highly comorbid with Alzheimer's disease and other neurodegenerative illnesses. The central role played by Aβ in the development of depressive-like symptoms in rodents has been evidenced in environmental rodent model of depression.

Early Celastrol Administration Prevents Ketamine-Induced Psychotic-Like Behavioral Dysfunctions, Oxidative Stress and IL-10 Reduction in The Cerebellum of Adult Mice.

Administration of subanesthetic doses of ketamine during brain maturation represents a tool to mimic an early insult to the central nervous system (CNS). The cerebellum is a key player in psychosis pathogenesis, to which oxidative stress also contributes. Here, we investigated the impact of early celastrol administration on behavioral dysfunctions in adult mice that had received ketamine (30 mg/kg i.

Ketamine administration induces early and persistent neurochemical imbalance and altered NADPH oxidase in mice.

Administration in adulthood of subanaesthetic doses of ketamine, an NMDA receptor (NMDA-R) antagonist, is commonly used to induce psychotic-like alterations in rodents. The NADPH oxidase (NOX) derived-oxidative stress has been shown to be implicated in ketamine-induced neurochemical dysfunctions and in the loss of parvalbumin (PV)-positive interneurons associated to the administration of this NMDA receptor antagonist in adult mice. However, very few data are available on the effects of early ketamine administration and its contribution to the development of long-term dysfunctions leading to psychosis.

Monoaminergic System Modulation in Depression and Alzheimer's Disease: A New Standpoint?

The prevalence of depression has dramatically increased, and it has been estimated that over 300 million people suffer from depression all over the world. Depression is highly comorbid with many central and peripheral disorders. In this regard, depressive states have been associated with the development of neurological disorders such as Alzheimer's disease (AD).

Increased iNOS and Nitrosative Stress in Dopaminergic Neurons of MDMA-Exposed Rats.

Several mechanisms underlying 3,4-Methylenedioxy--methylamphetamine (MDMA) neurotoxicity have been proposed, including neurochemical alterations and excitotoxicity mediated by reactive oxygen species (ROS), nitric oxide (NO), and reactive nitrogen species (RNS). However, ROS, NO, and RNS sources in the brain are not fully known. We aimed to investigate possible alterations in the expression of the ROS producer NOX enzymes (NOX2, NOX1, and NOX4), NO generators (iNOS, eNOS, and nNOS), markers of oxidative (8-hydroxy-2'-deoxyguanosine, 8OHdG), and nitrosative (3-nitrotyrosine, NT) stress, as well as the colocalization between cells positive for the dopamine transporter (DT1) and cells expressing the neuronal nuclei (NeuN) marker, in the frontal cortex of rats receiving saline or MDMA, sacrificed 6 h, 16 h, or 24 h after its administration.