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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 -
Bioengineering (Basel, Switzerland) Jun 2024Respiratory diseases are among the leading causes of death, with many individuals in a population frequently affected by various types of pulmonary disorders. Early...
Respiratory diseases are among the leading causes of death, with many individuals in a population frequently affected by various types of pulmonary disorders. Early diagnosis and patient monitoring (traditionally involving lung auscultation) are essential for the effective management of respiratory diseases. However, the interpretation of lung sounds is a subjective and labor-intensive process that demands considerable medical expertise, and there is a good chance of misclassification. To address this problem, we propose a hybrid deep learning technique that incorporates signal processing techniques. Parallel transformation is applied to adventitious respiratory sounds, transforming lung sound signals into two distinct time-frequency scalograms: the continuous wavelet transform and the mel spectrogram. Furthermore, parallel convolutional autoencoders are employed to extract features from scalograms, and the resulting latent space features are fused into a hybrid feature pool. Finally, leveraging a long short-term memory model, a feature from the latent space is used as input for classifying various types of respiratory diseases. Our work is evaluated using the ICBHI-2017 lung sound dataset. The experimental findings indicate that our proposed method achieves promising predictive performance, with average values for accuracy, sensitivity, specificity, and F1-score of 94.16%, 89.56%, 99.10%, and 89.56%, respectively, for eight-class respiratory diseases; 79.61%, 78.55%, 92.49%, and 78.67%, respectively, for four-class diseases; and 85.61%, 83.44%, 83.44%, and 84.21%, respectively, for binary-class (normal vs. abnormal) lung sounds.
PubMed: 38927822
DOI: 10.3390/bioengineering11060586 -
Biomedicines May 2024Alzheimer's disease (AD), the most common cause of dementia, is characterized by disruptions in memory, cognition, and personality, significantly impacting morbidity and...
Alzheimer's disease (AD), the most common cause of dementia, is characterized by disruptions in memory, cognition, and personality, significantly impacting morbidity and mortality rates among older adults. However, the exact pathophysiological mechanism of AD remains unknown, and effective treatment options for AD are still lacking. Human induced pluripotent stem cells (iPSC) are emerging as promising platforms for disease research, offering the ability to model the genetic mutations associated with various conditions. Patient-derived iPSCs are useful for modeling neurodegenerative and neurodevelopmental disorders. In this study, we generated AD iPSCs from peripheral blood mononuclear cells obtained from a 65-year-old patient with AD carrying the E682K mutation in the gene encoding the amyloid precursor protein. Cerebral organoids derived from AD iPSCs recapitulated the AD phenotype, exhibiting significantly increased levels of tau protein. Our analysis revealed that an iPSC disease model of AD is a valuable assessment tool for pathophysiological research and drug screening.
PubMed: 38927400
DOI: 10.3390/biomedicines12061193 -
Scientific Reports Jun 2024Classic psychedelics and MDMA have a colorful history of recreational use, and both have recently been re-evaluated as tools for the treatment of psychiatric disorders.... (Meta-Analysis)
Meta-Analysis
Classic psychedelics and MDMA have a colorful history of recreational use, and both have recently been re-evaluated as tools for the treatment of psychiatric disorders. Several studies have been carried out to assess potential long-term effects of a regular use on cognition, delivering distinct results for psychedelics and MDMA. However, to date knowledge is scarce on cognitive performance during acute effects of those substances. In this systematic review and meta-analysis, we investigate how cognitive functioning is affected by psychedelics and MDMA during the acute drug effects and the sub-acute ("afterglow") window. Our quantitative analyses suggest that acute cognitive performance is differentially affected by psychedelics when compared to MDMA: psychedelics impair attention and executive function, whereas MDMA primarily affects memory, leaving executive functions and attention unaffected. Our qualitative analyses reveal that executive functioning and creativity may be increased during a window of at least 24 h after the acute effects of psychedelics have subsided, whereas no such results have been observed for MDMA. Our findings may contribute to inform recommendations on harm reduction for recreational settings and to help fostering differential approaches for the use of psychedelics and MDMA within a therapeutic framework.
Topics: Humans; Hallucinogens; N-Methyl-3,4-methylenedioxyamphetamine; Cognition; Executive Function; Attention; Memory
PubMed: 38926480
DOI: 10.1038/s41598-024-65391-9 -
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 -
Schizophrenia Research Jun 2024Neurocognitive impairment is a core feature of schizophrenia spectrum disorders (SSDs), and the relationship between cognition and symptoms in SSDs has been widely...
BACKGROUND
Neurocognitive impairment is a core feature of schizophrenia spectrum disorders (SSDs), and the relationship between cognition and symptoms in SSDs has been widely researched. Negative symptoms are related to a wide range of cognitive impairments; however, the aspects of negative symptoms that underpin this relationship have yet to be specified.
STUDY DESIGN
We used iterative Constrained Principal Component Analysis (iCPCA) to explore the relationship between 18 cognitive measures (including processing speed, attention, working, spatial and verbal memory and executive functions) and 46 symptoms in schizophrenia at the individual item level while minimizing the risk of Type I errors. ICPCA was conducted on a sample of SSD patients in the early stages of psychiatric treatment (n = 121) to determine the components of cognition overlapping with symptoms measured by the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS).
RESULTS
We found that a verbal memory component was associated with items from SANS and SAPS related to impoverished and disorganized emotional communication, language, and thought. In contrast, a working memory component was associated with SANS items related to motor system impoverishment.
CONCLUSIONS
The iCPCA allowed us to explore the associations between individual items, optimized to understand the overlap between symptoms and cognition. The specific symptoms linked to verbal and working memory impairments imply distinct brain networks, which further investigation may lead to our deeper understanding of the illness and the development of treatment methods.
PubMed: 38924940
DOI: 10.1016/j.schres.2024.06.010 -
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 -
PloS One 2024The introduction of antiretroviral therapy (ART) has successfully changed the clinical course of people with HIV, leading to a significant decline in the incidence of...
The introduction of antiretroviral therapy (ART) has successfully changed the clinical course of people with HIV, leading to a significant decline in the incidence of HIV-related neurocognitive disorders. Integrase strand transferase inhibitors (INSTI) are recommended and preferred first-line ART for the treatment of HIV-1 infection in ART-naïve subjects. This type of therapy regimen is expected to have higher CNS penetration, which may bring more cognitive stability or even make significant cognitive improvement in people with HIV. The study aimed to follow up on neurocognitive performance in HIV subjects on two types of INSTI therapy regimens at two-time points, one year apart. The study sample consisted of 61 ART naïve male participants, of which 32 were prescribed raltegravir (RAL) and 29 dolutegravir (DTG). There was no significant difference between subsamples according to the main sociodemographic (age, education level) and clinical characteristics (duration of therapy, nadir CD4 cells level, CD4 cells count, CD8 cells, CD4/CD8 ratio). For neurocognitive assessment, six measures were used: general cognitive ability (MoCA test), verbal fluency (total sum score for phonemic and category fluency), verbal working memory (digit span forward), cognitive capacity (digit span backwards), sustained attention (Color Trail Test 1), and divided attention (Color Trail Test 2). In both therapy groups (RAL and DTG), there was no significant decrease in neurocognitive achievement on all used measures over a one-year follow-up in both therapy groups. A statistically significant interactive effect of time and type of therapy was found on the measure of divided attention-DTG group showed slight improvement, whereas RAL group showed slight decrease in performance. During the one-year follow-up of persons on INSTI-based regimen, no significant changes in cognitive achievement were recorded, which suggests that the existing therapy can have a potentially positive effect on the maintenance of neurocognitive achievement.
Topics: Humans; Male; HIV Infections; Adult; Follow-Up Studies; Cognition; Raltegravir Potassium; HIV Integrase Inhibitors; Middle Aged; Pyridones; Piperazines; Heterocyclic Compounds, 3-Ring; Oxazines; Neuropsychological Tests; HIV-1
PubMed: 38923982
DOI: 10.1371/journal.pone.0306278 -
Pathogens (Basel, Switzerland) Jun 2024Within the last two decades, SARS-CoV-2 was the third zoonotic severe acute respiratory betacoronavirus (sarbecovirus) to infect humans, following SARS and MERS. The...
Within the last two decades, SARS-CoV-2 was the third zoonotic severe acute respiratory betacoronavirus (sarbecovirus) to infect humans, following SARS and MERS. The disruptions caused by the pandemic underscore the need for a universal vaccine against respiratory betacoronaviruses. Our group previously developed the universal platform for vaccine development, MultiTEP, which has been utilized in this study to generate a range of SARS-CoV-2 epitope vaccine candidates. We prepared and characterized 18 vaccines incorporating small peptide fragments from SARS-CoV-2 Spike protein fused with the MultiTEP sequence using overlapping PCR. Wild-type mice were immunized intramuscularly with the immunogen formulated in AdvaxCpG adjuvant. Serum antibodies were detected by ELISA, surrogate neutralization, and pseudovirus neutralization assays. Finally, the most promising vaccine candidate was administered to three non-human primates. All vaccines generated high titers of spike-binding IgG antibodies. However, only three vaccines generated antibodies that blocked RBD binding to the ACE2 receptor in a surrogate virus neutralization assay. However, none of the vaccines induced antibodies able to neutralize pseudotype viruses, including after the administration of the lead vaccine to NHPs. MultiTEP-based COVID-19 vaccines elicited robust, IgG-binding responses against the Spike protein in mice and non-human primates, but these antibodies were not neutralizing, underscoring the need to refine this approach further.
PubMed: 38921817
DOI: 10.3390/pathogens13060520 -
Pediatric Reports May 2024Klinefelter syndrome (KS), also known as 47,XXY, is a genetic disorder characterized by the presence of an extra X chromosome. Despite the prevalence of verbal learning... (Review)
Review
Klinefelter syndrome (KS), also known as 47,XXY, is a genetic disorder characterized by the presence of an extra X chromosome. Despite the prevalence of verbal learning disabilities, memory impairments, and executive function deficits in individuals with KS, comprehensive research on the neuropsychological profiles of affected children and adolescents remains limited. Additionally, KS has been associated with comorbid conditions such as depression, anxiety, schizophrenia, attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorders (ASDs). However, systematic investigations into the neuropsychological manifestations of KS in pediatric populations are scarce. Therefore, the primary objectives of this review are to provide an overview of key studies examining the neuropsychological profiles of children and adolescents with KS and to delineate the limitations and implications of existing research findings. By synthesizing available literature, this review aims to bridge the gap in understanding the cognitive and behavioral characteristics of children and adolescents with KS, shedding light on potential avenues for future research and clinical interventions. Ultimately, this review serves as a valuable resource for clinicians, researchers, policymakers, parents, and educators involved in the assessment and management of the neuropsychological aspects of Klinefelter syndrome in pediatric populations.
PubMed: 38921701
DOI: 10.3390/pediatric16020036