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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 -
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 -
Current Issues in Molecular Biology Jun 2024Semaglutide (SEM), a glucagon-like peptide-1 receptor agonist, has garnered increasing interest for its potential therapeutic effects in neurodegenerative disorders such... (Review)
Review
Semaglutide (SEM), a glucagon-like peptide-1 receptor agonist, has garnered increasing interest for its potential therapeutic effects in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). This review provides a comprehensive description of SEM's mechanism of action and its effects in preclinical studies of these debilitating conditions. In animal models of AD, SEM has proved beneficial effects on multiple pathological hallmarks of the disease. SEM administration has been associated with reductions in amyloid-beta plaque deposition and mitigation of neuroinflammation. Moreover, SEM treatment has been shown to ameliorate behavioral deficits related to anxiety and social interaction. SEM-treated animals exhibit improvements in spatial learning and memory retention tasks, as evidenced by enhanced performance in maze navigation tests and novel object recognition assays. Similarly, in animal models of PD, SEM has demonstrated promising neuroprotective effects through various mechanisms. These include modulation of neuroinflammation, enhancement of mitochondrial function, and promotion of neurogenesis. Additionally, SEM has been shown to improve motor function and ameliorate dopaminergic neuronal loss, offering the potential for disease-modifying treatment strategies. Overall, the accumulating evidence from preclinical studies suggests that SEM holds promise as a novel therapeutic approach for AD and PD. Further research is warranted to elucidate the underlying mechanisms of SEM's neuroprotective effects and to translate these findings into clinical applications for the treatment of these devastating neurodegenerative disorders.
PubMed: 38921025
DOI: 10.3390/cimb46060354 -
Behavioral Sciences (Basel, Switzerland) Jun 2024(1) Background: Previous studies have identified discrepancies in improvements in executive functioning in typically developing children when comparing closed- and... (Review)
Review
Effects of Practicing Closed- vs. Open-Skill Exercises on Executive Functions in Individuals with Attention Deficit Hyperactivity Disorder (ADHD)-A Meta-Analysis and Systematic Review.
(1) Background: Previous studies have identified discrepancies in improvements in executive functioning in typically developing children when comparing closed- and open-skill exercise interventions. However, there is limited research on executive functioning in attention deficit hyperactivity disorder (ADHD). This study aims to conduct a systematic review and meta-analysis to explore the impact of closed- and open-skill exercises on ADHD populations. (2) Methods: The PRISMA guidelines for systematic reviews were followed to search seven databases to evaluate and analyze studies published from 2013 to 2023. Prospero: CRD42023460452. (3) Results: A meta-analysis of 578 subjects with ADHD in 11 RCTs (Randomized control trial) and 3 NRS (Non-randomized studies) revealed that closed-skill exercise significantly improved executive function subdomains, including inhibitory control (standardized mean differences (SMD) = -1.00), cognitive flexibility (SMD = -1.33), and working memory (SMD = -0.85). Furthermore, open-skill exercise was found to have a positive effect on inhibitory control (SMD = -1.98) and cognitive flexibility (SMD = -0.97) in ADHD patients. Both types of exercise interventions demonstrated an improvement in executive function compared to controls, with open-skill exercises exhibiting superior effects (Q = 6.26). (4) Conclusions: The review recommends a 12-week intervention cycle with exercise at least twice a week of moderate or higher intensity as suitable for ADHD individuals. This review also encourages individuals with ADHD to engage in exercises involving multiple motor skill types.
PubMed: 38920831
DOI: 10.3390/bs14060499 -
Behavioral Sciences (Basel, Switzerland) May 2024Associations and families demand the need to raise awareness of the implications in the cognitive and behavioral development of children with Fetal Alcohol Spectrum...
Associations and families demand the need to raise awareness of the implications in the cognitive and behavioral development of children with Fetal Alcohol Spectrum Disorder (FASD) that affect their learning and school participation. This study aims to generate a profile of executive and behavioral functioning in children and adolescents diagnosed with FASD. A probabilistic sampling by clusters (associations for individuals with FASD) is applied. The sample is composed of 66 families from three associations. The BRIEF-2 and SENA tests were administered to assess executive and behavioral functioning domains. Data analysis found that the executive and behavioral functioning profile of individuals with FASD varies with age, with greater impairment in middle and late adolescence. Likewise, the domain of executive functioning most affected in any of the developmental stages is working memory. Finally, cognitive impairment in the executive functioning domains has a direct impact on the social and adaptive functioning of people with FASD.
PubMed: 38920763
DOI: 10.3390/bs14060431