Defining Phenotype, Tropism, and Retinal Gene Therapy Using Adeno-Associated Viral Vectors (AAVs) in New-Born Brown Norway Rats with a Spontaneous Mutation in .

Mutations in the Crumbs homologue 1 () gene cause inherited retinal dystrophies, such as early-onset retinitis pigmentosa and Leber congenital amaurosis. A Brown Norway rat strain was reported with a spontaneous insertion-deletion (indel) mutation in exon 6 of . It has been reported that these mutant rats show vascular abnormalities associated with retinal telangiectasia and possess an early-onset retinal degenerative phenotype with outer limiting membrane breaks and focal loss of retinal lamination at 2 months of age.

Reactive astrocytes as treatment targets in Alzheimer's disease-Systematic review of studies using the APPswePS1dE9 mouse model.

Astrocytes regulate synaptic communication and are essential for proper brain functioning. In Alzheimer's disease (AD) astrocytes become reactive, which is characterized by an increased expression of intermediate filament proteins and cellular hypertrophy. Reactive astrocytes are found in close association with amyloid-beta (Aβ) deposits.

EEG spectral analysis in insomnia disorder: A systematic review and meta-analysis.

Insomnia disorder (ID) has become the second-most common mental disorder. Despite burgeoning evidence for increased high-frequency electroencephalography (EEG) activity and cortical hyperarousal in ID, the detailed spectral features of this disorder during wakefulness and different sleep stages remain unclear. Therefore, we adopted a meta-analytic approach to systematically assess existing evidence on EEG spectral features in ID.

Histamine H receptor deletion in cholinergic neurons induces sensorimotor gating ability deficit and social impairments in mice.

Negative symptoms in schizophrenia strongly contribute to poor functional outcomes, however its pathogenesis is still unclear. Here, we found that histamine H receptor (HR) expression in basal forebrain (BF) cholinergic neurons was decreased in patients with schizophrenia having negative symptoms. Deletion of HR gene in cholinergic neurons in mice resulted in functional deficiency of cholinergic projections from the BF to the prefrontal cortex and in the formation of sensorimotor gating deficit, social impairment and anhedonia-like behavior.

Shedding light on light exposure in elderly with intellectual disabilities.

Background: Light exposure affects mood and sleep regulation. Sleep problems and mood complaints are common in elderly with intellectual disabilities (ID) living in care facilities. Insufficient light exposure is hypothesised to contribute to the high prevalence of these problems.

Electric field strength induced by electroconvulsive therapy is associated with clinical outcome.

The clinical effect of electroconvulsive therapy (ECT) is mediated by eliciting a generalized seizure, which is achieved by applying electrical current to the head via scalp electrodes. The anatomy of the head influences the distribution of current flow in each brain region. Here, we investigated whether individual differences in simulated local electrical field strength are associated with ECT efficacy.

The GTPase Rab8 differentially controls the long- and short-range activity of the Hedgehog morphogen gradient by regulating Hedgehog apico-basal distribution.

The Hedgehog (Hh) morphogen gradient is required for patterning during metazoan development, yet the mechanisms involved in Hh apical and basolateral release and how this influences short- and long-range target induction are poorly understood. We found that depletion of the GTPase Rab8 in Hh-producing cells induces an imbalance between the level of apically and laterally released Hh. This leads to non-cell-autonomous differential effects on the expression of Hh target genes, namely an increase in its short-range targets and a concomitant decrease in long-range targets.

Risk-Based Decision Making: A Systematic Scoping Review of Animal Models and a Pilot Study on the Effects of Sleep Deprivation in Rats.

Animals, including humans, frequently make decisions involving risk or uncertainty. Different strategies in these decisions can be advantageous depending the circumstances. Short sleep duration seems to be associated with more risky decisions in humans.

Deep brain stimulation versus ablative surgery for treatment-refractory obsessive-compulsive disorder: A meta-analysis.

Objective: Ablative surgery (ABL) and deep brain stimulation (DBS) are last-resort treatment options for patients suffering from treatment-refractory obsessive-compulsive disorder (OCD). The aim of this study was to conduct an updated meta-analysis comparing the clinical outcomes of the ablative procedures capsulotomy and cingulotomy and deep brain stimulation.

Methods: We conducted a PubMed search to identify all clinical trials on capsulotomy, cingulotomy, and DBS.

Macrophage-Derived Inflammation Induces a Transcriptome Makeover in Mesenchymal Stromal Cells Enhancing Their Potential for Tissue Repair.

Pre-clinical and clinical studies revealed that mesenchymal stromal cell (MSC) transplants elicit tissue repair. Conditioning MSC prior to transplantation may boost their ability to support repair. We investigated macrophage-derived inflammation as a means to condition MSC by comprehensively analyzing their transcriptome and secretome.

Combining Gamma With Alpha and Beta Power Modulation for Enhanced Cortical Mapping in Patients With Focal Epilepsy.

About one third of patients with epilepsy have seizures refractory to the medical treatment. Electrical stimulation mapping (ESM) is the gold standard for the identification of "eloquent" areas prior to resection of epileptogenic tissue. However, it is time-consuming and may cause undesired side effects.

The adult human subventricular zone: partial ependymal coverage and proliferative capacity of cerebrospinal fluid.

Neurogenesis continues throughout adulthood in specialized regions of the brain. One of these regions is the subventricular zone. During brain development, neurogenesis is regulated by a complex interplay of intrinsic and extrinsic cues that control stem-cell survival, renewal and cell lineage specification.

Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis.

The repair of inflamed, demyelinated lesions as in multiple sclerosis (MS) necessitates the clearance of cholesterol-rich myelin debris by microglia/macrophages and the switch from a pro-inflammatory to an anti-inflammatory lesion environment. Subsequently, oligodendrocytes increase cholesterol levels as a prerequisite for synthesizing new myelin membranes. We hypothesized that lesion resolution is regulated by the fate of cholesterol from damaged myelin and oligodendroglial sterol synthesis.

Cognitive behavioral therapy for misophonia: A randomized clinical trial.

Background: Patients with misophonia suffer from anger or disgust confronted with specific sounds such as smacking or breathing. Avoidance of cue-related situations results in social isolation and significant functional impairment. This is the first randomized, controlled cognitive behavioral therapy (CBT) trial for misophonia, evaluating the short- and long-term efficacy.

Brain structural correlates of insomnia severity in 1053 individuals with major depressive disorder: results from the ENIGMA MDD Working Group.

It has been difficult to find robust brain structural correlates of the overall severity of major depressive disorder (MDD). We hypothesized that specific symptoms may better reveal correlates and investigated this for the severity of insomnia, both a key symptom and a modifiable major risk factor of MDD. Cortical thickness, surface area and subcortical volumes were assessed from T1-weighted brain magnetic resonance imaging (MRI) scans of 1053 MDD patients (age range 13-79 years) from 15 cohorts within the ENIGMA MDD Working Group.

Histamine-4 receptor antagonist ameliorates Parkinson-like pathology in the striatum.

Growing evidence indicates that microglia activation and a neuroinflammatory trigger contribute to dopaminergic cell loss in Parkinson's disease (PD). Furthermore, increased density of histaminergic fibers and enhanced histamine levels have been observed in the substantia nigra of PD-postmortem brains. Histamine-induced microglial activation is mediated by the histamine-4 receptor (HR).

Comparison of sleep-wake rhythms in elderly persons with intellectual disabilities and the general population.

Background: Sleep problems are common in people with intellectual disabilities (ID), but the knowledge on the natural course of sleep-wake rhythms and sleep problems in elderly persons with ID is limited. In the current study, objectively measured sleep-wake rhythms and the prevalence and severity of sleep problems of elderly persons with ID was compared to that of healthy elderly persons from a large representative sample from the general population.

Methods: Actigraphy data of 501 elderly persons with ID (age 62.

Early-life stress alters affective behaviors in adult mice through persistent activation of CRH-BDNF signaling in the oval bed nucleus of the stria terminalis.

Early-life stress (ELS) leads to stress-related psychopathology in adulthood. Although dysfunction of corticotropin-releasing hormone (CRH) signaling in the bed nucleus of the stria terminalis (BNST) mediates chronic stress-induced maladaptive affective behaviors that are historically associated with mood disorders such as anxiety and depression, it remains unknown whether ELS affects CRH function in the adult BNST. Here we applied a well-established ELS paradigm (24 h maternal separation (MS) at postnatal day 3) and assessed the effects on CRH signaling and electrophysiology in the oval nucleus of BNST (ovBNST) of adult male mouse offspring.

The Circadian Clock, Shift Work, and Tissue-Specific Insulin Resistance.

Obesity and type 2 diabetes (T2D) have become a global health concern. The prevalence of obesity and T2D is significantly higher in shift workers compared to people working regular hours. An accepted hypothesis is that the increased risk for metabolic health problems arises from aberrantly timed eating behavior, that is, eating out of synchrony with the biological clock.

7 Tesla MRI Followed by Histological 3D Reconstructions in Whole-Brain Specimens.

magnetic resonance imaging (MRI) studies on the human brain are of great interest for the validation of MRI. It facilitates a link between functional and anatomical information available from MRI and neuroanatomical knowledge available from histology/immunocytochemistry. However, linking and MRI to microscopy techniques poses substantial challenges.

Object Selection by Automatic Spreading of Top-Down Attentional Signals in V1.

What is selected when attention is directed to a specific location of the visual field? Theories of object-based attention have suggested that when spatial attention is directed to part of an object, attention does not simply enhance the attended location but automatically spreads to enhance all locations that comprise the object. Here, we tested this hypothesis by reconstructing the distribution of attention from primary visual cortex (V1) population neuronal activity patterns in 24 human adults (17 female) using functional magnetic resonance imaging (fMRI) and population-based receptive field (prf) mapping. We find that attention spreads from a spatially cued location to the underlying object, and enhances all spatial locations that comprise the object.

Sex differences in stress-related disorders: Major depressive disorder, bipolar disorder, and posttraumatic stress disorder.

Stress-related disorders, such as mood disorders and posttraumatic stress disorder (PTSD), are more common in women than in men. This sex difference is at least partly due to the organizing effect of sex steroids during intrauterine development, while activating or inhibiting effects of circulating sex hormones in the postnatal period and adulthood also play a role. Such effects result in structural and functional changes in neuronal networks, neurotransmitters, and neuropeptides, which make the arousal- and stress-related brain systems more vulnerable to environmental stressful events in women.

Identifying Plasma Biomarkers with high specificity for major depressive disorder: A multi-level proteomics study.

Background: There are currently no objective diagnostic biomarkers for major depressive disorder (MDD) due to the biological complexity of the disorder. The existence of blood-based biomarkers with high specificity would be convenient for the clinical diagnosis of MDD.

Methods: A comprehensive plasma proteomic analysis was conducted in a highly homogeneous cohort [7 drug-naïve MDD patients and 7 healthy controls (HCs)], with bioinformatics analysis combined with machine learning used to screen candidate proteins.

Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link.

Serotonin (5-HT) is a critical player in brain development and neuropsychiatric disorders. Fetal 5-HT levels can be influenced by several gestational factors, such as maternal genotype, diet, stress, medication, and immune activation. In this review, addressing both human and animal studies, we discuss how these gestational factors affect placental and fetal brain 5-HT levels, leading to changes in brain structure and function and behavior.