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Advanced Science (Weinheim,... Aug 2023Autism spectrum disorders (ASDs) include a wide range of neurodevelopmental disorders. Several reports showed that mutations in different high-risk ASD genes lead to...
Autism spectrum disorders (ASDs) include a wide range of neurodevelopmental disorders. Several reports showed that mutations in different high-risk ASD genes lead to ASD. However, the underlying molecular mechanisms have not been deciphered. Recently, they reported a dramatic increase in nitric oxide (NO) levels in ASD mouse models. Here, they conducted a multidisciplinary study to investigate the role of NO in ASD. High levels of nitrosative stress biomarkers are found in both the Shank3 and Cntnap2 ASD mouse models. Pharmacological intervention with a neuronal NO synthase (nNOS) inhibitor in both models led to a reversal of the molecular, synaptic, and behavioral ASD-associated phenotypes. Importantly, treating iPSC-derived cortical neurons from patients with SHANK3 mutation with the nNOS inhibitor showed similar therapeutic effects. Clinically, they found a significant increase in nitrosative stress biomarkers in the plasma of low-functioning ASD patients. Bioinformatics of the SNO-proteome revealed that the complement system is enriched in ASD. This novel work reveals, for the first time, that NO plays a significant role in ASD. Their important findings will open novel directions to examine NO in diverse mutations on the spectrum as well as in other neurodevelopmental disorders. Finally, it suggests a novel strategy for effectively treating ASD.
Topics: Mice; Animals; Autism Spectrum Disorder; Nitric Oxide; Neurons; Biomarkers; Microfilament Proteins; Nerve Tissue Proteins
PubMed: 37212048
DOI: 10.1002/advs.202205783 -
International Journal of Psychological... 2023Stress is fundamental for health and adaptation; it is an evolutionarily conserved response that involves several systems in the organism. The study of the stress...
Stress is fundamental for health and adaptation; it is an evolutionarily conserved response that involves several systems in the organism. The study of the stress response could be traced back to the end of the nineteenth century with George Beard's or Claude Bernard's work and, from that moment on, several studies that have allowed the elucidation of its neurobiology and the consequences of suffering from it were consolidated. In this theoretical review, we discuss the most relevant researches to our knowledge on the study of stress response, from the concept of stress, its neurobiology, the hormonal response during stress, as well as its regulation, the effects of acute and chronic stress, stress from cognition, the different stress responses during life, as well as its relationship with different psychiatric disorders. Taken together, the reviewed research updates the classic perspective on stress, increasing the factors that should be considered in research to explore the effects of stress on health.
PubMed: 38106958
DOI: 10.21500/20112084.5815 -
Sleep Science (Sao Paulo, Brazil) Sep 2023Sleep has important clinical implications for neurorehabilitation after stroke. We aimed to systematically explore sleep (including naps) as an essential factor in the... (Review)
Review
Sleep has important clinical implications for neurorehabilitation after stroke. We aimed to systematically explore sleep (including naps) as an essential factor in the neurorehabilitation of patients after stroke. After titles and abstracts were screened, 49 full texts were reviewed, and 7 were included in this review. Data were extracted and assessed for quality and risk of bias. We looked at any neurorehabilitation setting, and compared sleep with no sleep and explored these factors in stroke patients versus healthy individuals. Rehabilitation is critical for many activities that may need to be learned or re-learned following stroke and for returning to everyday life. In this context, sleep is essential in neurorehabilitation and physical therapy practice as it supports neuroplasticity, memory, and learning. The available data suggest that sleep should be considered in the treatment plan for successfully targeted physiotherapy to optimize cognitive and motor learning. Physical therapists should advise about sleep hygiene and therapies to improve sleep, both quality and quantity.
PubMed: 38196757
DOI: 10.1055/s-0043-1772805 -
Journal of Intelligence Nov 2023In this paper, we propose an application of critical thinking (CT) to real-world problems, taking into account personal well-being (PB) and lifelong formation (FO)....
In this paper, we propose an application of critical thinking (CT) to real-world problems, taking into account personal well-being (PB) and lifelong formation (FO). First, we raise a substantial problem with CT, which is that causal explanation is of little importance in solving everyday problems. If we care about everyday problems, we must treat the identification of causal relationships as a fundamental mechanism and action as a form of solution once the origin of the problem is unequivocally known. Decision-making and problem-solving skills should be the execution of the causal explanations reached. By acting this way, we change reality and achieve our goals, which are none other than those imposed by our PB. However, to achieve changes or results, we must have these fundamental competencies in CT, and these are not innate; we must acquire and develop them, that is, we must train ourselves to have CT competencies according to the demands of today's world. Finally, in this paper we propose a causal model that seeks to identify and test the causal relationships that exist between the different factors or variables that determine the CT-PB-FO relationship. We present some results on the relevance of causality and how to effectively form and address real-world problems from causality. However, there are still questions to be clarified that need to be investigated in future studies.
PubMed: 38132837
DOI: 10.3390/jintelligence11120219 -
Nature Communications Nov 2023Pathological placental inflammation increases the risk for several adult disorders, but these mediators are also expressed under homeostatic conditions, where their...
Pathological placental inflammation increases the risk for several adult disorders, but these mediators are also expressed under homeostatic conditions, where their contribution to adult health outcomes is unknown. Here we define an inflammation-related expression signature, primarily expressed in Hofbauer cells of the term placenta and use expression quantitative trait loci to create a polygenic score (PGS) predictive of its expression. Using this PGS in the UK Biobank we conduct a phenome-wide association study, followed by Mendelian randomization and identify protective, sex-dependent effects of the placental module on cardiovascular and depressive outcomes. Genes differentially regulated by intra-amniotic infection and preterm birth are over-represented within the module. We also identify aspirin as a putative modulator of this inflammation-related signature. Our data support a model where disruption of placental Hofbauer cell function, due to preterm birth or prenatal infection, contributes to the increased risk of depression and cardiovascular disease observed in these individuals.
Topics: Adult; Pregnancy; Female; Infant, Newborn; Humans; Placenta; Premature Birth; Cardiovascular System; Inflammation; Cardiovascular Diseases
PubMed: 37963865
DOI: 10.1038/s41467-023-42300-8 -
Obesity Reviews : An Official Journal... Aug 2023Midlife obesity and late-life weight loss confer a greater risk for developing dementia and Alzheimer's disease (AD), but the exact mechanisms behind this phenomenon are... (Meta-Analysis)
Meta-Analysis Review
Midlife obesity and late-life weight loss confer a greater risk for developing dementia and Alzheimer's disease (AD), but the exact mechanisms behind this phenomenon are currently unknown. The answer could lie on the involvement of gastrointestinal factors, such as adipokines (e.g., leptin, adiponectin, and resistin) and ghrelin. In this context, we conducted a pre-registered systematic review and meta-analysis of 42 cross-sectional and 13 longitudinal studies targeting the associations between leptin, adiponectin, resistin, and ghrelin and the prevalence of general dementia, AD, and mild cognitive impairment (MCI). We also examined the relationship between the four gastrointestinal factors and neurocognitive outcomes and AD-related cerebrospinal fluid biomarkers. Patients with AD had lower blood leptin and higher resistin levels than cognitively normal participants. Lower leptin and higher resistin were associated with higher degree of cognitive impairment. Additionally, lower late-life leptin levels might be associated with higher prospective risk of dementia and AD, although more studies are needed to corroborate this. Results in ghrelin and adiponectin were not conclusive, with age, sex distribution, obesity, and severity of dementia seemingly acting as moderators across several analyses. Our work might contribute to the identification of new preclinical blood markers of MCI and AD.
Topics: Humans; Adipokines; Alzheimer Disease; Leptin; Resistin; Adiponectin; Ghrelin; Cross-Sectional Studies; Prospective Studies; Cognitive Dysfunction; Biomarkers; Obesity
PubMed: 37165483
DOI: 10.1111/obr.13573 -
Sleep Medicine Clinics Dec 2023There is an increased risk of becoming pregnant through fertility treatments using assisted reproductive technology (ART) during the COVID-19 pandemic. The aim of this... (Review)
Review
There is an increased risk of becoming pregnant through fertility treatments using assisted reproductive technology (ART) during the COVID-19 pandemic. The aim of this review is to gather comprehensive data from the existing literature on the potential risks of fertility management during the pandemic period, and outline strategies to mitigate them, with a focus on the hormonal and surgical procedures of ART. A comprehensive search of the scientific literature on COVID-19 in relation to fertility was conducted in the PubMed database using the keywords "coronavirus," "COVID-19," "SARS-CoV-2" and "pregnancy," "fertility," "urogenital system," "vertical transmission," "assisted human reproduction," "controlled ovarian stimulation," "oocyte retrieval," "in vitro fertilization," "hormones," "surgical procedures," "embryos," "oocytes," "sperm," "semen," "ovary," "testis," "ACE-2 receptor," "immunology," "cytokine storm," and "coagulation," from January 2020-July 2022. Published data on pregnancy and COVID-19, and the interaction of the urogenital system and SARS-CoV-2 is reported. The immunologic and prothrombotic profiles of patients with COVID-19, and their increased risks from controlled ovarian stimulation (COS) and ART surgeries, and how these procedures could facilitate COVID-19 and/or contribute to the severity of the disease by enhancing the cytokine storm are summarized. Strategies to prevent complications during COS that could increase the risks of the disease in pre-symptomatic patients are considered. The impact of SARS-CoV-2 on pre-symptomatic infertile patients presents a challenge to find ways to avoid the increased hormonal, immunologic, and prothrombotic risks presented by the use of COS in ART protocols during the COVID-19 outbreak. Safe ART procedures and recommendations are highlighted.
Topics: Female; Humans; Male; Pregnancy; COVID-19; Cytokine Release Syndrome; SARS-CoV-2; Reproductive Techniques, Assisted
PubMed: 38501521
DOI: 10.1016/j.jsmc.2023.06.012 -
Neuroscience and Biobehavioral Reviews Sep 2023The Rorschach inkblot test allows access to psychological processes that usually do not emerge in self-report measures and it has been widely used in clinical... (Review)
Review
The Rorschach inkblot test allows access to psychological processes that usually do not emerge in self-report measures and it has been widely used in clinical psychological and psychiatric settings. Recordings of brain activity during the administration of the Rorschach inkblots test could provide information on neural correlates of the underlying perceptual-cognitive processing and potentially identify neuroimaging markers of psychopathology risk. The present paper offers a systematization of the available literature on the Rorschach inkblot test and neuroimaging research. The 13 selected studies had been conducted with healthy participants and using fMRI, EEG, and fNIRS to investigate the neural underpinnings of Rorschach inkblot test responses. The neural processes underlying the visual, social, and emotional processes described by the included papers are systematically summarized. Research on the neural correlates of the Rorschach inkblot test is promising and would further benefit from studies on clinical populations, broader samples, and younger age groups.
Topics: Humans; Rorschach Test; Emotions
PubMed: 37311472
DOI: 10.1016/j.neubiorev.2023.105281 -
Journal of Neuroinflammation Sep 2023Most current disease-modifying therapies approved for multiple sclerosis (MS) are immunomodulatory drugs that counteract the aberrant activity of the immune system....
BACKGROUND
Most current disease-modifying therapies approved for multiple sclerosis (MS) are immunomodulatory drugs that counteract the aberrant activity of the immune system. Hence, new pharmacological interventions that drive anti-inflammatory activity and neuroprotection would represent interesting alternative therapeutic approaches or complementary strategies to treat progressive forms of MS. There is evidence of reduced noradrenaline levels and alterations to locus coeruleus (LC) noradrenergic neurons in MS patients, as well as in animal models of this disease, potentially factors contributing to the pathophysiology. Drugs that enhance noradrenaline appear to have some beneficial effects in MS, suggesting their potential to dampen the underlying pathology and disease progression.
METHODS
Therefore, we explored the consequences of chronic LC noradrenergic neurons activation by chemogenetics in experimental autoimmune encephalomyelitis (EAE) mice, the most widely used experimental model of MS. LC activation from the onset or the peak of motor symptoms was explored as two different therapeutic approaches, assessing the motor and non-motor behavioral changes as EAE progresses, and studying demyelination, inflammation and glial activation in the spinal cord and cerebral cortex during the chronic phase of EAE.
RESULTS
LC activation from the onset of motor symptoms markedly alleviated the motor deficits in EAE mice, as well as their anxiety-like behavior and sickness, in conjunction with reduced demyelination and perivascular infiltration in the spinal cord and glial activation in the spinal cord and prefrontal cortex (PFC). When animals exhibited severe paralysis, LC activation produced a modest alleviation of EAE motor symptoms and it enhanced animal well-being, in association with an improvement of the EAE pathology at the spinal cord and PFC level. Interestingly, the reduced dopamine beta-hydroxylase expression associated with EAE in the spinal cord and PFC was reversed through chemogenetic LC activation.
CONCLUSION
Therefore, clear anti-inflammatory and neuroprotective effects were produced by the selective activation of LC noradrenergic neurons in EAE mice, having greater benefits when LC activation commenced earlier. Overall, these data suggest noradrenergic LC neurons may be targets to potentially alleviate some of the motor and non-motor symptoms in MS.
Topics: Animals; Mice; Multiple Sclerosis; Locus Coeruleus; Encephalomyelitis, Autoimmune, Experimental; Adrenergic Neurons; Norepinephrine
PubMed: 37658434
DOI: 10.1186/s12974-023-02865-z -
Neuroscience Aug 2023This chapter presents a brief overview of attachment theory and discusses the importance of the neonatal period in shaping an individual's physiological and behavioural... (Review)
Review
This chapter presents a brief overview of attachment theory and discusses the importance of the neonatal period in shaping an individual's physiological and behavioural responses to stress later in life, with a focus on the role of the parent-infant relationship, particularly in rodents. In rodents, the role of maternal behaviours goes far beyond nutrition, thermoregulation and excretion, acting as hidden regulators of the pup's physiology and development. In this review, we will discuss the inhibitory role of specific maternal behaviours on the ACTH and corticosterone (CORT) stress response. The interest of our group to explore the long-term consequences of maternal deprivation for 24 h (DEP) at different ages (3 days and 11 days) in rats was sparked by its opposite effects on ACTH and CORT levels. In early adulthood, DEP3 animals (males and females alike) show greater negative impact on affective behaviours and stress related parameters than DEP11, indicating that the latter is more resilient in tests of anxiety-like behaviour. These findings create an opportunity to explore the neurobiological underpinnings of vulnerability and resilience to stress-related disorders. The chapter also provides a brief historical overview and highlights the relevance of attachment theory, and how DEP helps to understand the effects of childhood parental loss as a risk factor for depression, schizophrenia, and PTSD in both childhood and adulthood. Furthermore, we present the concept of environmental enrichment (EE), its effects on stress responses and related behavioural changes and its benefits for rats previously subjected to DEP, along with the clinical implications of DEP and EE.
Topics: Male; Humans; Female; Rats; Animals; Brain; Maternal Behavior; Anxiety; Corticosterone; Maternal Deprivation; Adrenocorticotropic Hormone; Stress, Psychological
PubMed: 37352967
DOI: 10.1016/j.neuroscience.2023.06.013