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Brain Sciences Jun 2024This study examines the impact of response and semantic inhibition on scientific reasoning using fNIRS data from 30 students (15 male, 15 female). Utilizing Go/Nogo and...
This study examines the impact of response and semantic inhibition on scientific reasoning using fNIRS data from 30 students (15 male, 15 female). Utilizing Go/Nogo and Stroop-like tasks within a modified speeded-reasoning task, it was found that inhibition significantly influences scientific reasoning. Specifically, slower responses and lower accuracy on incongruent statements were linked to increased activity in bilateral dorsolateral prefrontal cortex (DLPFC) and pre-supplementary motor area (pre-SMA). The research shows that both DLPFC and pre-SMA are associated with overcoming misconceptions in scientific reasoning. The findings suggest that understanding inhibitory mechanisms can enhance educational strategies to improve critical thinking and scientific literacy.
PubMed: 38928606
DOI: 10.3390/brainsci14060606 -
International Journal of Molecular... Jun 2024Cannabidiol (CBD), a phytocannabinoid, appeared to satisfy several criteria for a safe approach to preventing drug-taking behavior, including opioids. However, most...
Cannabidiol (CBD), a phytocannabinoid, appeared to satisfy several criteria for a safe approach to preventing drug-taking behavior, including opioids. However, most successful preclinical and clinical results come from studies in adult males. We examined whether systemic injections of CBD (10 mg/kg, i.p.) during extinction of oxycodone (OXY, 3 mg/kg, i.p.) induced conditioned place preference (CPP) could attenuate the reinstatement of CPP brought about by OXY (1.5 mg/kg, i.p.) priming in adolescent rats of both sexes, and whether this effect is sex dependent. Accordingly, a priming dose of OXY produced reinstatement of the previously extinguished CPP in males and females. In both sexes, this effect was linked to locomotor sensitization that was blunted by CBD pretreatments. However, CBD was able to prevent the reinstatement of OXY-induced CPP only in adolescent males and this outcome was associated with an increased cannabinoid 1 receptor (CB1R) and a decreased mu opioid receptor (MOR) expression in the prefrontal cortex (PFC). The reinstatement of CCP in females was associated with a decreased MOR expression, but no changes were detected in CB1R in the hippocampus (HIP). Moreover, CBD administration during extinction significantly potentialized the reduced MOR expression in the PFC of males and showed a tendency to potentiate the reduced MOR in the HIP of females. Additionally, CBD reversed OXY-induced deficits of recognition memory only in males. These results suggest that CBD could reduce reinstatement to OXY seeking after a period of abstinence in adolescent male but not female rats. However, more investigation is required.
Topics: Animals; Cannabidiol; Male; Female; Oxycodone; Rats; Receptor, Cannabinoid, CB1; Receptors, Opioid, mu; Prefrontal Cortex; Analgesics, Opioid; Conditioning, Psychological
PubMed: 38928357
DOI: 10.3390/ijms25126651 -
International Journal of Molecular... Jun 2024Epidemiological data suggest that moderate hyperoxemia may be associated with an improved outcome after traumatic brain injury. In a prospective, randomized...
Epidemiological data suggest that moderate hyperoxemia may be associated with an improved outcome after traumatic brain injury. In a prospective, randomized investigation of long-term, resuscitated acute subdural hematoma plus hemorrhagic shock (ASDH + HS) in 14 adult, human-sized pigs, targeted hyperoxemia (200 < PO < 250 mmHg vs. normoxemia 80 < PO < 120 mmHg) coincided with improved neurological function. Since brain perfusion, oxygenation and metabolism did not differ, this post hoc study analyzed the available material for the effects of targeted hyperoxemia on cerebral tissue markers of oxidative/nitrosative stress (nitrotyrosine expression), blood-brain barrier integrity (extravascular albumin accumulation) and fluid homeostasis (oxytocin, its receptor and the HS-producing enzymes cystathionine-β-synthase and cystathionine-γ-lyase). After 2 h of ASDH + HS (0.1 mL/kgBW autologous blood injected into the subdural space and passive removal of 30% of the blood volume), animals were resuscitated for up to 53 h by re-transfusion of shed blood, noradrenaline infusion to maintain cerebral perfusion pressure at baseline levels and hyper-/normoxemia during the first 24 h. Immediate postmortem, bi-hemispheric (i.e., blood-injected and contra-lateral) prefrontal cortex specimens from the base of the sulci underwent immunohistochemistry (% positive tissue staining) analysis of oxidative/nitrosative stress, blood-brain barrier integrity and fluid homeostasis. None of these tissue markers explained any differences in hyperoxemia-related neurological function. Likewise, hyperoxemia exerted no deleterious effects.
Topics: Animals; Swine; Hematoma, Subdural, Acute; Shock, Hemorrhagic; Brain; Blood-Brain Barrier; Immunohistochemistry; Oxidative Stress; Resuscitation; Disease Models, Animal; Oxygen; Tyrosine
PubMed: 38928283
DOI: 10.3390/ijms25126574 -
International Journal of Molecular... Jun 2024Glutamate is the main excitatory neurotransmitter in the brain wherein it controls cognitive functional domains and mood. Indeed, brain areas involved in memory... (Review)
Review
Glutamate is the main excitatory neurotransmitter in the brain wherein it controls cognitive functional domains and mood. Indeed, brain areas involved in memory formation and consolidation as well as in fear and emotional processing, such as the hippocampus, prefrontal cortex, and amygdala, are predominantly glutamatergic. To ensure the physiological activity of the brain, glutamatergic transmission is finely tuned at synaptic sites. Disruption of the mechanisms responsible for glutamate homeostasis may result in the accumulation of excessive glutamate levels, which in turn leads to increased calcium levels, mitochondrial abnormalities, oxidative stress, and eventually cell atrophy and death. This condition is known as glutamate-induced excitotoxicity and is considered as a pathogenic mechanism in several diseases of the central nervous system, including neurodevelopmental, substance abuse, and psychiatric disorders. On the other hand, these disorders share neuroplasticity impairments in glutamatergic brain areas, which are accompanied by structural remodeling of glutamatergic neurons. In the current narrative review, we will summarize the role of glutamate-induced excitotoxicity in both the pathophysiology and therapeutic interventions of neurodevelopmental and adult mental diseases with a focus on autism spectrum disorders, substance abuse, and psychiatric disorders. Indeed, glutamatergic drugs are under preclinical and clinical development for the treatment of different mental diseases that share glutamatergic neuroplasticity dysfunctions. Although clinical evidence is still limited and more studies are required, the regulation of glutamate homeostasis is attracting attention as a potential crucial target for the control of brain diseases.
Topics: Humans; Glutamic Acid; Mental Disorders; Animals; Neurodevelopmental Disorders; Neuronal Plasticity; Brain; Adult; Substance-Related Disorders; Autism Spectrum Disorder
PubMed: 38928227
DOI: 10.3390/ijms25126521 -
DNA Damage and Senescence in the Aging and Alzheimer's Disease Cortex Are Not Uniformly Distributed.Biomedicines Jun 2024Alzheimer's disease (AD) is a neurodegenerative illness with a typical age of onset exceeding 65 years of age. The age dependency of the condition led us to track the...
Alzheimer's disease (AD) is a neurodegenerative illness with a typical age of onset exceeding 65 years of age. The age dependency of the condition led us to track the appearance of DNA damage in the frontal cortex of individuals who died with a diagnosis of AD. The focus on DNA damage was motivated by evidence that increasing levels of irreparable DNA damage are a major driver of the aging process. The connection between aging and the loss of genomic integrity is compelling because DNA damage has also been identified as a possible cause of cellular senescence. The number of senescent cells has been reported to increase with age, and their senescence-associated secreted products are likely contributing factors to age-related illnesses. We tracked DNA damage with 53BP1 and cellular senescence with p16 immunostaining of human post-mortem brain samples. We found that DNA damage was significantly increased in the BA9 region of the AD cortex compared with the same region in unaffected controls (UCs). In the AD but not UC cases, the density of cells with DNA damage increased with distance from the pia mater up to approximately layer V and then decreased in deeper areas. This pattern of DNA damage was overlaid with the pattern of cellular senescence, which also increased with cortical depth. On a cell-by-cell basis, we found that the intensities of the two markers were tightly linked in the AD but not the UC brain. To test whether DNA damage was a causal factor in the emergence of the senescence program, we used etoposide treatment to damage the DNA of cultured mouse primary neurons. While DNA damage increased after treatment, after 24 h, no change in the expression of senescence-associated markers was observed. Our work suggests that DNA damage and cellular senescence are both increased in the AD brain and increasingly coupled. We propose that in vivo, the relationship between the two age-related processes is more complex than previously thought.
PubMed: 38927534
DOI: 10.3390/biomedicines12061327 -
Biomedicines Jun 2024Vascular dementia, the second most common type of dementia, currently lacks a definitive cure. In the pursuit of therapies aimed at slowing its progression and...
Vascular dementia, the second most common type of dementia, currently lacks a definitive cure. In the pursuit of therapies aimed at slowing its progression and alleviating symptoms, transcranial direct current stimulation (tDCS) emerges as a promising approach, characterized by its non-invasive nature and the ability to promote brain plasticity. In this study, the primary objective was to investigate the effects of a two-week cycle of tDCS on the dorsolateral prefrontal cortex (DLPFC) and neurophysiological functioning in thirty patients diagnosed with vascular dementia. Each participant was assigned to one of two groups: the experimental group, which received anodal tDCS to stimulate DPCFL, and the control group, which received sham tDCS. Neurophysiological functions were assessed before and after tDCS using P300 event-related potentials (ERPs), while neuropsychological function was evaluated through a Mini-Mental State Examination (MMSE). The results showed a reduction in P300 latency, indicating a faster cognitive process; an increase in P300 amplitude, suggesting a stronger neural response to cognitive stimuli; and a significant improvement in MMSE scores compared to the control group, indicating an overall enhancement in cognitive functions. These findings suggest that tDCS could represent a promising therapeutic option for improving both neurophysiological and cognitive aspects in patients with vascular dementia.
PubMed: 38927497
DOI: 10.3390/biomedicines12061290 -
Nature Communications Jun 2024Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples,...
Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries offer more nuanced and accurate insights into the regulatory mechanisms of RNA editing in the human brain.
Topics: Humans; RNA Editing; Adenosine; Adenosine Deaminase; Brain; Inosine; RNA-Binding Proteins; Autopsy; Prefrontal Cortex; Postmortem Changes; Male
PubMed: 38926387
DOI: 10.1038/s41467-024-49268-z -
Brain, Behavior, and Immunity Jun 2024Influenza A virus (IAV) infection during pregnancy can increase the risk for neurodevelopmental disorders in the offspring, however, the underlying neurobiological...
Influenza A virus (IAV) infection during pregnancy can increase the risk for neurodevelopmental disorders in the offspring, however, the underlying neurobiological mechanisms are largely unknown. To recapitulate viral infection, preclinical studies have traditionally focused on using synthetic viral mimetics, rather than live IAV, to examine consequences of maternal immune activation (MIA)-dependent processes on offspring. In contrast, few studies have used live IAV to assess effects on global gene expression, and none to date have addressed whether moderate IAV, mimicking seasonal influenza disease, alters normal gene expression trajectories in different brain regions across different stages of development. Herein, we show that moderate IAV infection during pregnancy, which causes mild maternal disease and no overt foetal complications in utero, induces lasting effects on the offspring into adulthood. We observed behavioural changes in adult offspring, including disrupted pre-pulse inhibition, dopaminergic hyper-responsiveness, and spatial recognition memory deficits. Gene profiling in the offspring brain from neonate to adolescence revealed persistent alterations to normal gene expression trajectories in the hippocampus, cerebellum, prefrontal cortex, and hypothalamus. Alterations were found in genes involved in inflammation and neurogenesis, which were predominately dysregulated in neonatal and early adolescent offspring. Notably, late adolescent offspring born from IAV infected mice displayed altered microglial morphology in the hippocampus. In conclusion, we show that moderate IAV during pregnancy perturbs neurodevelopmental trajectories in the offspring, including alterations in the neuroinflammatory gene expression profiled and microglial number and morphology in the hippocampus, resulting in behavioural changes in adult offspring. Such early perturbations may underlie the vulnerability in human offspring for the later development of neurodevelopmental disorders, including schizophrenia. Our work highlights the importance of using live IAV in developing novel preclinical models that better recapitulate the real-world impact of inflammatory insults during pregnancy on the offspring neurodevelopmental trajectory and disease susceptibility later in life.
PubMed: 38925418
DOI: 10.1016/j.bbi.2024.06.025 -
Toxicology Jun 2024Fmr1 (fragile X messenger ribonucleoprotein 1)-knockout (KO) rats, modeling the human Fragile X Syndrome (FXS), are of particular interest for exploring the ASD-like...
Fmr1 (fragile X messenger ribonucleoprotein 1)-knockout (KO) rats, modeling the human Fragile X Syndrome (FXS), are of particular interest for exploring the ASD-like phenotype in preclinical studies. Gestational exposure to chlorpyrifos (CPF) has been associated with ASD diagnosis in humans and ASD-like behaviors in rodents and linked to the microbiota-gut-brain axis. In this study, we have used both Fmr1-KO and wild-type male rats (F2 generation) at postnatal days (PND) 7 and 40 obtained after F1 pregnant females were randomly exposed to 1mg/kg/mL/day of CPF or vehicle. A nuclear magnetic resonance (NMR) metabolomics approach together with gene expression profiles of these F2 generation rats were employed to analyze different brain regions (such as prefrontal cortex, hippocampus, and cerebellum), whole large intestine (at PND7) and gut content (PND40). The statistical comparison of each matrix spectral profile unveiled tissue-specific metabolic fingerprints. Significant variations in some biomarker levels were detected among brain tissues of different genotypes, including taurine, myo-inositol, and 3-hydroxybutyric acid, and exposure to CPF induced distinct metabolic alterations, particularly in serine and myo-inositol. Additionally, this study provides a set of metabolites associated with gastrointestinal dysfunction in ASD, encompassing several amino acids, choline-derived compounds, bile acids, and sterol molecules. In terms of gene expression, genotype and gestational exposure to CPF had only minimal effects on decarboxylase 2 (gad2) and cholinergic receptor muscarinic 2 (chrm2) genes.
PubMed: 38925359
DOI: 10.1016/j.tox.2024.153871 -
Psychoneuroendocrinology Jun 2024Hormonal changes in ovarian hormones like estradiol (E2) during the menstrual cycle affect emotional processes, including emotion recognition, memory, and regulation. So...
Hormonal changes in ovarian hormones like estradiol (E2) during the menstrual cycle affect emotional processes, including emotion recognition, memory, and regulation. So far, the neural underpinnings of the effect of E2 on emotional experience have been investigated using task-based functional magnetic resonance imaging (fMRI) and functional connectivity. In the present study, we examined whether the intrinsic network dynamics at rest (i.e., directed effective connectivity) related to emotion regulation are (1) modulated by E2 levels and (2) linked to behavioral emotion regulation ability. Hence, 29 naturally cycling women participated in two resting-state fMRI scans in their early follicular phase after being administered a placebo or an E2 valerate, respectively. Emotion regulation ability was assessed using a standard emotion regulation task in which participants were asked to down-regulate their emotions in response to negative images. The regions of two functionally predefined neural networks related to emotional down-regulation and reactivity were used to investigate effective connectivity at rest using spectral dynamic causal modelling. We found that E2, compared to placebo, resulted in changes in effective connectivity in both networks. In the regulation network, prefrontal regions showed distinct connectivity in the E2 compared to the placebo condition, while mixed results evolved in the emotional reactivity network. Stepwise regressions revealed that in the E2 condition a connection from the parietal to the prefrontal cortex predicted regulation ability. Our results demonstrate that E2 levels influence effective connectivity in networks underlying emotion regulation and emotional reactivity. Thus, E2 and its potential modification via hormonal administration may play a supporting role in the treatment of mental disorders that show a dysregulation of emotions.
PubMed: 38924828
DOI: 10.1016/j.psyneuen.2024.107103