Biomarkers.

Background: Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia. Its underlying mechanisms remain elusive and specific mechanism-based drugs are lacking.

Method: We integrated more than 2,800 CSF and 4,600 plasma pQTL, derived from the largest proteomic studies so far (SOMAscan 7k and 4k; in up to 35,559 individuals), and the two most prevalent MRI-markers of cSVD (MRI-cSVD, white matter hyperintensities and perivascular spaces burden; in up to 48,454 individuals) in a Mendelian Randomization (MR) framework to identify causal and druggable targets for cSVD.

Optogenetic targeting of cortical astrocytes selectively improves NREM sleep in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by memory impairments and distinct histopathological features such as amyloid-beta (Aβ) accumulations. Alzheimer's patients experience sleep disturbances at early stages of the disease. APPswe/PS1dE9 (APP) mice exhibit sleep disruptions, including reductions in non-rapid eye movement (NREM) sleep, that contribute to their disease progression.

The influence of paraventricular nucleus of the hypothalamus soluble guanylate cyclase on autonomic and neuroendocrine responses to acute restraint stress in rats.

The paraventricular nucleus of the hypothalamus (PVN) regulates physiological and behavioural responses evoked by stressful stimuli, but the local neurochemical and signalling mechanisms involved are not completely understood. The soluble guanylate cyclase (sGC) within the PVN is implicated in autonomic and cardiovascular control in rodents under resting conditions. However, the involvement of PVN sGC-mediated signalling in stress responses is unknown.

Correlational Insights into Attention-Deficit/Hyperactivity Disorder in Lebanon.

Attention-Deficit/Hyperactivity Disorder (ADHD), a prevalent childhood neurodevelopmental disorder with complex etiology involving genetic and environmental factors, causes impairments across various life domains and substantial social and economic burden. Identifying correlates to prevent its onset and decrease its incidence is crucial. To our knowledge, our study represents the first case-control investigation of Lebanese ADHD patients to explore potential correlations between familial, maternal, and child health variables and ADHD to enhance understanding of its etiology and aid in prevention efforts.

The neoliberal leaning of the neuroscience discourse when it deals with mental health and learning disorders.

Neuroscience attracted increasing attention in mass media during the last decades. Indeed, neuroscience advances raise high expectations in society concerning major societal issues such as mental health and learning difficulties. Unfortunately, according to leading experts, neuroscience advances have not yet benefited patients, students and socially deprived families.

Prediction of dementia risk from multimodal repeated measures: The added value of brain MRI biomarkers.

Abstract: The utility of brain magnetic resonance imaging (MRI) for predicting dementia is debated. We evaluated the added value of repeated brain MRI, including atrophy and cerebral small vessel disease markers, for dementia prediction. We conducted a landmark competing risk analysis in 1716 participants of the French population-based Three-City Study to predict the 5-year risk of dementia using repeated measures of 41 predictors till year 4 of follow-up.

Slow wave activity disruptions and memory impairments in a mouse model of aging.

The aging population suffers from memory impairments. Slow-wave activity (SWA) is composed of slow (0.5-1 Hz) and delta (1-4 Hz) oscillations, which play important roles in long-term memory and working memory function respectively.

NB-02 Protects Neurons and Astrocytes from Oligomeric Amyloid-β-Mediated Damage.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with limited therapeutic strategies. NB-02 is a novel botanical drug that has shown promise as a protective and therapeutic treatment for AD in an APP/PS1 preclinical mouse model. In this paper, we investigate the underlying mechanisms by which NB-02 provides these therapeutic advantages using in vitro neuron-astrocyte co-cultures.

Near-Infrared II Photobiomodulation Preconditioning Ameliorates Stroke Injury via Phosphorylation of eNOS.

Background: The current management of patients with stroke with intravenous thrombolysis and endovascular thrombectomy is effective only when it is timely performed on an appropriately selected but minor fraction of patients. The development of novel adjunctive therapy is highly desired to reduce morbidity and mortality with stroke. Since endothelial dysfunction is implicated in the pathogenesis of stroke and is featured with suppressed endothelial nitric oxide synthase (eNOS) with concomitant nitric oxide deficiency, restoring endothelial nitric oxide represents a promising approach to treating stroke injury.

P2X4 signalling contributes to hyperactivity but not pain sensitization comorbidity in a mouse model of attention deficit/hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by hyperactivity, inattention, and impulsivity that often persist until adulthood. Frequent comorbid disorders accompany ADHD and two thirds of children diagnosed with ADHD also suffer from behavioural disorders and from alteration of sensory processing. We recently characterized the comorbidity between ADHD-like symptoms and pain sensitisation in a pharmacological mouse model of ADHD, and we demonstrated the implication of the anterior cingulate cortex and posterior insula.

ENDOCANNABINOID SYSTEM IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS MODULATES AUTONOMIC AND CARDIOVASCULAR CHANGES BUT NOT VASOPRESSIN RESPONSE IN A RAT HEMORRHAGIC SHOCK MODEL.

We evaluated the participation of the endocannabinoid system in the paraventricular nucleus of the hypothalamus (PVN) on the cardiovascular, autonomic, and plasma vasopressin (AVP) responses evoked by hemorrhagic shock in rats. For this, the PVN was bilaterally treated with either vehicle, the selective cannabinoid receptor type 1 antagonist AM251, the selective fatty acid amide hydrolase amide enzyme inhibitor URB597, the selective monoacylglycerol-lipase enzyme inhibitor JZL184, or the selective transient receptor potential vanilloid type 1 antagonist capsazepine. We evaluated changes on arterial pressure, heart rate, tail skin temperature (ST), and plasma AVP responses induced by bleeding, which started 10 min after PVN treatment.

Sleep restoration by optogenetic targeting of GABAergic neurons reprograms microglia and ameliorates pathological phenotypes in an Alzheimer's disease model.

Background: Alzheimer's disease (AD) patients exhibit memory disruptions and profound sleep disturbances, including disruption of deep non-rapid eye movement (NREM) sleep. Slow-wave activity (SWA) is a major restorative feature of NREM sleep and is important for memory consolidation.

Methods: We generated a mouse model where GABAergic interneurons could be targeted in the presence of APPswe/PS1dE9 (APP) amyloidosis, APP-GAD-Cre mice.

Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration.

Parkinson's disease (PD) targets some dopamine (DA) neurons more than others. Sex differences offer insights, with females more protected from DA neurodegeneration. The mammalian vesicular glutamate transporter VGLUT2 and ortholog dVGLUT have been implicated as modulators of DA neuron resilience.

Visceral and Subcutaneous Abdominal Fat Predict Brain Volume Loss at Midlife in 10,001 Individuals.

Abdominal fat is increasingly linked to brain health. A total of 10,001 healthy participants were scanned on 1.5T MRI with a short whole-body MR imaging protocol.

A Critical Review of Zebrafish Neurological Disease Models-2. Application: Functional and Neuroanatomical Phenotyping Strategies and Chemical Screens.

Extensive phylogenetic conservation of molecular pathways and neuroanatomical structures, associated with efficient methods for genetic modification, have been exploited increasingly to generate zebrafish models of human disease. A range of powerful approaches can be deployed to analyze these models with the ultimate goal of elucidating pathogenic mechanisms and accelerating efforts to find effective treatments. Unbiased neurobehavioral assays can provide readouts that parallel clinical abnormalities found in patients, although some of the most useful assays quantify responses that are not routinely evaluated clinically, and differences between zebrafish and human brains preclude expression of the full range of neurobehavioral abnormalities seen in disease.

Optogenetic targeting of astrocytes restores slow brain rhythm function and slows Alzheimer's disease pathology.

Patients with Alzheimer's disease (AD) exhibit non-rapid eye movement (NREM) sleep disturbances in addition to memory deficits. Disruption of NREM slow waves occurs early in the disease progression and is recapitulated in transgenic mouse models of beta-amyloidosis. However, the mechanisms underlying slow-wave disruptions remain unknown.

Prelimbic Cortical Stimulation Induces Antidepressant-like Responses through Dopaminergic-Dependent and -Independent Mechanisms.

High-frequency stimulation (HFS) is a promising therapy for patients with depression. However, the mechanisms underlying the HFS-induced antidepressant-like effects on susceptibility and resilience to depressive-like behaviors remain obscure. Given that dopaminergic neurotransmission has been found to be disrupted in depression, we investigated the dopamine(DA)-dependent mechanism of the antidepressant-like effects of HFS of the prelimbic cortex (HFS PrL).

Calcium sensor Yellow Cameleon 3.6 as a tool to support the calcium hypothesis of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is a neurodegenerative disease with increasing relevance as dementia cases rise. The etiology of AD is widely debated. The Calcium Hypothesis of Alzheimer's disease and brain aging states that the dysfunction of calcium signaling is the final common pathway leading to neurodegeneration.