Search Results (7,165)

Prolactin is a hormone with demonstrated roles in the brain, including neurogenesis, neuroprotection, learning, stress response or memory consolidation. To determine the prolactin expression in the rat hippocampus during aging and to resolve some controversies related to the presence of prolactin in the hippocampus, the aim of this study was to analyze whether changes occur in the expression of prolactin during different stages of life. To determine this, we designed an experimental study in which we analyzed the expression and location of prolactin in the rat hippocampus, Ammon’s horn and Dentate Gyrus, during different stages of life (prepubertal, postpubertal, young adult, adult and old) and checked if there are differences related to sex. Overall, the results obtained show that prolactin is present in the rat hippocampus and that prolactin is synthesized, as deduced from the findings obtained via ELISA, immunohistochemistry, qPCR and in situ hybridization. After analyzing the correlation between serum and hippocampal prolactin levels and comparing the amounts of Prl mRNA and the hormone, the results obtained suggest that hippocampal prolactin has a dual origin: local synthesis of the hormone and its passage from the blood. On the other hand, the amounts of prolactin and its mRNA in the hippocampus vary with sex and age, suggesting the existence of age-related sexual dimorphism. The results obtained suggest that hippocampal aging is related to a decrease in the hippocampal prolactin system, which helps to better understand brain aging. Full article

Tetrabromobisphenol A (TBBPA) is a brominated flame retardant widely used in consumer products. TBBPA is often detected in soil, water, organisms, and even in human blood and breast milk. Hence, it is accessible to developing fetuses and nursing offspring after maternal exposure. The reported evidence for the endocrine disruption of TBBPA in the brain has raised concerns regarding its effects on neurodevelopmental and behavioral functions. This study investigated the effects of TBBPA exposure on neurodevelopment. A cell-based developmental neurotoxicity assay was performed to determine whether TBBPA is a developmental neurotoxicant. The assay revealed TBBPA to be a developmental neurotoxicant. C57BL/6N maternal mice were administered TBBPA at 0, 0.24, and 2.4 mg/kg during pregnancy and lactation, and their offspring underwent behavioral testing. The behavioral experiments revealed sex-specific effects. In females, only a deterioration of the motor ability was observed. In contrast, deteriorations in motor function, memory, and social interaction were noted in males. Furthermore, we validated changes in the expression of genes associated with behavioral abnormalities, confirming that perinatal exposure to TBBPA, at the administered doses, can affect neurodevelopment and behavior in offspring. These findings highlight the need for more in-depth and multifaceted research on the toxicity of TBBPA. Full article

Background/Objectives: The objective of this study was to validate a new parent-reported scale for tracking Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). PANS is a condition characterized by a sudden and severe onset of neuropsychiatric symptoms. To meet diagnostic criteria, an individual must present with either obsessive–compulsive disorder (OCD) or severely restricted food intake, accompanied by at least two additional cognitive, behavioral, or emotional symptoms. These may include anxiety, emotional instability, depression, irritability, aggression, oppositional behaviors, developmental or behavioral regression, a decline in academic skills such as handwriting or math, sensory abnormalities, frequent urination, and enuresis. The onset of symptoms is usually triggered by an infection or an abnormal immune/inflammatory response. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a subtype of PANS specifically linked to strep infections. Methods: We developed a 101-item PANS/PANDAS and Related Inflammatory Brain Disorders Treatment Evaluation Checklist (PTEC) designed to assess changes to a patient’s symptoms over time along 10 subscales: Behavior/Mood, OCD, Anxiety, Food intake, Tics, Cognitive/Developmental, Sensory, Other, Sleep, and Health. The psychometric quality of PTEC was tested with 225 participants. Results: The internal reliability of the PTEC was excellent (Cronbach’s alpha = 0.96). PTEC exhibited adequate test–retest reliability (r = 0.6) and excellent construct validity, supported by a strong correlation with the Health subscale of the Autism Treatment Evaluation Checklist (r = 0.8). Conclusions: We hope that PTEC will assist parents and clinicians in the monitoring and treatment of PANS. The PTEC questionnaire is freely available at neuroimmune.org/PTEC. Full article

The balance between physiological, psychological, and environmental factors often shapes human experience. In recent years, research has drawn attention to the gut microbiota as a significant contributor to brain function and emotional regulation. This narrative review examines how changes in gut microbiota may relate to depression. We selected studies that explore the link between intestinal dysbiosis and mood, focusing on mechanisms such as inflammation, vagus nerve signaling, HPA axis activation, gut permeability, and neurotransmitter balance. Most of the available data come from animal models, but findings from human studies suggest similar patterns. Findings are somewhat difficult to compare due to differences in measurement procedures and patient groups. However, several microbial shifts have been observed in people with depressive symptoms, and trials with probiotics or fecal microbiota transplant show potential. These results remain limited. We argue that these interventions deserve more attention, especially in cases of treatment-resistant or inflammation-driven depression. Understanding how the gut and brain interact could help define clearer subtypes of depression and guide new treatment approaches. Full article

Military personnel deployed to Iraq and Afghanistan were exposed to emissions from open-air burn pits, where plastics, metals, and medical waste were incinerated. These exposures have been linked to deployment-related respiratory diseases (DRRD) and may also impact neurological health via the lung–brain axis. To investigate molecular mechanisms, adult male rats were exposed to filtered air, naphthalene (a representative volatile organic compound), or a combination of naphthalene and carbon black (surrogate for particulate matter; CBN) via whole-body inhalation (six hours/day, three consecutive days). Lung, brain, and plasma samples were collected 24 h after the final exposure. Pro-inflammatory biomarkers were assessed using multiplex electrochemiluminescence and western blot. Differentially expressed genes (DEGs) were identified by RNA sequencing, and elastic net modeling was used to define exposure-predictive gene signatures. CBN exposure altered inflammatory biomarkers across tissues, with activation of nuclear factor kappa B (NF-κB) signaling. In the lung, gene set enrichment revealed activated pathways related to proliferation and inflammation, while epithelial–mesenchymal transition (EMT) and oxidative phosphorylation were suppressed. In the brain, EMT, inflammation, and senescence pathways were activated, while ribosomal function and oxidative metabolism were downregulated. Elastic net modeling identified a lung gene signature predictive of CBN exposure, including Kcnq3, Tgfbr1, and Tm4sf19. These findings demonstrate that inhalation of a surrogate burn pit mixture induces inflammatory and metabolic gene expression changes in both lung and brain tissues, supporting the utility of this animal model for understanding systemic effects of airborne military toxicants and for identifying potential biomarkers relevant to DRRD and Veteran health. Full article

Background and objectives: Neurosurgical intervention on the newborn’s developing brain is a risk factor for neurodevelopmental disorders (NDDs). These patients necessarily require regular, coordinated follow-up. The ventricular subgaleal shunt (VSGS) technique has been used since 2013 at Rouen University Hospital. Like any change in practice, this technique must be evaluated. In this paper, we describe the population of patients with hydrocephalus treated by VSGS, the complications associated with the procedure, and the outcome of these patients at two and six years old. Methods: This study was an observational, descriptive, retrospective, single-center study. Children included were those less than three months old with hydrocephalus treated by VSGS at Rouen University Hospital from January 2013 to December 2023. Data were anonymized and collected using EDSaN software. A descriptive analysis was performed. Results: Thirty-two patients were included in our study. Of these, 22 (69%) were born prematurely; 16 (50%) of these 22 had postnatal intraventricular hemorrhage (IVH) requiring treatment with VSGS. A total of three patients (13.6%) died within the first year of life; twenty-four patients (75%) required definitive shunting. Twenty-two patients were over 2 years old in our study. Only 10 of them acquired the ability to walk (45%). Cerebral palsy was present in 10 (45%) patients. Fifteen patients were over 6 years old; thirteen (87%) attended school, but six (40%) had special needs (the need of an assistant, or part-time schedule). In our study, only 24 patients (82%) were followed by a pediatrician trained in neurodevelopment at Rouen University Hospital, and 27 (93%) were followed by a neurosurgeon. Conclusions: This study describes all patients with hydrocephalus treated by VSGS at Rouen University Hospital between January 2013 and December 2023, as well as their complications and their neurological outcomes. The follow-up of these children at risk of NDDs is essential. Full article

The stochastic variance-reduced gradient (SVRG) theory is particularly well-suited for addressing gradient variance in deep neural network (DNN) training; however, its direct application to DNN training is hindered by adaptation challenges. To tackle this issue, the present paper proposes a series of strategies focused on adaptive alternating learning rates to effectively adapt SVRG for DNN training. Firstly, within the outer loop of SVRG, both the full gradient and the learning rate specific to DNN training are computed. For two distinct formulas used for calculating the learning rate, an alternating strategy is introduced that employs them alternately across iterations. This approach allows for simultaneous provision of diverse guidance information regarding parameter change rates and gradient change rates during DNN weight updates. Additionally, a threshold method is utilized to correct the learning rate into an appropriate range, thereby accelerating convergence. Secondly, in the inner loop of SVRG, DNN weights are updated using mini-batch average gradient along with the proposed learning rate. Concurrently, mini-batch average gradients from each iteration within the inner loop are refined and aggregated into a single gradient exhibiting reduced variance through an inertia strategy. This refined gradient is then relayed back to the outer loop to recalculate the new learning rate. The efficacy of the proposed algorithm has been validated on models including LeNet, VGG11, ResNet34, and DenseNet121 while being compared against several classic and advanced optimizers. Experimental results demonstrate that the proposed algorithm exhibits remarkable training robustness across DNN models with diverse characteristics. In terms of training convergence, the proposed algorithm demonstrates competitiveness with state-of-the-art algorithms, such as Lion, developed by the Google Brain team. Full article

The effective suppression of inflammation using disease-modifying therapies is essential in the treatment of multiple sclerosis (MS). Anti-CD20 monoclonal antibodies are commonly used long-term as maintenance therapies, largely due to the lack of reliable biomarkers to guide dosing and evaluate treatment response. However, prolonged use increases the risk of infections and other immune-mediated side effects. The unique ability of brain-derived blood extracellular vesicles (EVs) to cross the blood–brain barrier and reflect the central nervous system (CNS) immune status has sparked interest in their potential as biomarkers. This study aimed to assess whether blood-derived L1CAM⁺ EVs could serve as biomarkers of treatment response to rituximab (RTX) in patients with relapsing-remitting MS (RRMS). Serum samples (n = 25) from the baseline (month 0) and after 6 months were analyzed from the RTX arm of the ongoing randomized clinical trial OVERLORD-MS (comparing anti-CD20 therapies in RRMS patients) and were compared with serum samples from healthy controls (n = 15). Baseline cerebrospinal fluid (CSF) samples from the same study cohort were also included. EVs from both serum and CSF samples were characterized, considering morphology, size, and concentration, using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). The immunophenotyping of EV surface receptors was performed using flow cytometry with the MACSPlex exosome kit, while label-free quantitative proteomics of EV protein cargo was conducted using a proximity extension assay (PEA). TEM confirmed the presence of EVs with the expected round morphology with a diameter of 50–150 nm. NTA showed significantly higher concentrations of L1CAM⁺ EVs (p < 0.0001) in serum total EVs and EBNA1⁺ EVs (p < 0.01) in serum L1CAM⁺ EVs at baseline (untreated) compared to in healthy controls. After six months of RTX therapy, there was a significant reduction in L1CAM⁺ EV concentration (p < 0.0001) and the downregulation of TNFRSF13B (p = 0.0004; FC = −0.49) in serum total EVs. Additionally, non-significant changes were observed in CD79B and CCL2 levels in serum L1CAM⁺ EVs at baseline compared to in controls and after six months of RTX therapy. In conclusion, L1CAM⁺ EVs in serum showed distinct immunological profiles before and after rituximab treatment, underscoring their potential as dynamic biomarkers for individualized anti-CD20 therapy in MS. Full article

(1) Background: Evidence from non-human animal and spaceflight analog studies have suggested that traveling to outer space could have a significant impact on the structural properties of the hippocampus, a brain region within the medial temporal lobe that is critical for learning and memory. Here, we tested this hypothesis in a group of astronauts who participated in a six-month mission in the International Space Station (ISS). (2) Methods: We collected magnetic resonance imaging (MRI) scans from a sample of 17 (9 males, 8 females) astronauts before and after the ISS mission, and calculated percent gray matter volume changes in the whole hippocampus and its (anterior, body, and posterior) subregions in both hemispheres. (3) Following the six-month mission in the ISS, we found a significantly decreased volume in the whole left hippocampus; in addition, when looking at subregions separately, we detected a significantly decreased volume in the anterior subregion of the left hippocampus and the body subregion of the right hippocampus. We also found a significantly decreased volume in the whole right hippocampus of male astronauts as compared to female astronauts. (4) Conclusions: This study, providing the very first evidence of hippocampal volumetric changes in astronauts following a six-month mission to the ISS, could have significant implications for cognitive performance during future long-duration spaceflights. Full article

Despite decades of intense interest and investment in cognitive science, there remains a not only incomplete but also highly inconsistent body of evidence regarding how adult brains recover from even the most focal injuries associated with stroke. In this paper, I provide a broad narrative review of the studies of post-stroke aphasia recovery that have sought to identify the mechanisms of language recovery through longitudinal functional imaging. I start with studies that used functional imaging in groups of neurotypical individuals that have revealed areas of the brain that are reliably activated by language tasks and are functionally connected, referred to here as the “language network.” I then review group studies in which functional imaging data were averaged across groups of people with post-stroke aphasia to characterize the neurobiology of recovery. These group studies of post-stroke aphasia have yielded very different results and have led to conflicting conclusions. Subsequently, I examine results of studies of single subjects that have employed longitudinal functional imaging to identify mechanisms of language recovery. Together, these single subject studies make it clear that mechanisms of neural recovery are far from uniform, even in people with very similar lesions and time since stroke. On this basis, I argue that it is not justifiable to average functional imaging data across individuals with post-stroke aphasia to draw meaningful insights into how brain networks change to support language recovery. Each individual’s brain networks change over time, but in divergent ways that depend on the extent of disruption to the normal language network, interventions to facilitate recovery, the health of the intact brain, and other variables yet to be identified. While averaging results across participants with post-stroke aphasia might be able to identify certain changes in the networks that are correlated with specific language gains, uncovering the range of mechanisms and dynamics of language recovery after stroke requires longitudinal imaging of individuals. Full article

Objective: This study aimed to explore the acute neurophysiological effects of a single oral dose of Astragaloside IV (AS-IV) on EEG-measured brain oscillations and cognitive-relevant spectral markers in healthy young adults. Methods: Twenty healthy adults (8 females, 12 males; mean age: $23.4\pm 2.1$) underwent eyes-closed resting-state EEG recordings before and approximately 90 min after oral intake of 150 mg AS-IV. EEG data were collected using a 21-channel 10–20 system and cleaned via Artifact Subspace Reconstruction and Independent Component Analysis. Data quality was confirmed using a signal-to-noise ratio and 1/f spectral slope. Absolute and relative power values, band ratios, and frontal alpha asymmetry were computed. Statistical comparisons were made using paired t-tests or Wilcoxon signed-rank tests. Results: Absolute power decreased in delta, theta, beta, and gamma bands (p < 0.05) but remained stable for alpha. Relative alpha power increased significantly (p = 0.002), with rises in relative beta, theta, and delta and a drop in relative gamma (p = 0.003). Alpha/beta and theta/beta ratios increased, while delta/alpha decreased. Frontal alpha asymmetry was unchanged. Sex differences were examined in all measures that showed significant changes; however, no sex-dependent effects were found. Conclusions: A single AS-IV dose may acutely modulate brain oscillations, supporting its potential neuroactive properties. Larger placebo-controlled trials, including concurrent psychometric assessments, are needed to verify and contextualize these findings. A single AS-IV dose may acutely modulate brain oscillations, supporting its potential neuroactive properties. Full article

Clinical and animal studies suggest that multiple brain systems are involved in mediating reward-motivated and related emotional behavior including the consumption of commonly used drugs and palatable food, and there is evidence that the repeated ingestion of or exposure to these rewarding substances may in turn stimulate these brain systems to produce an overconsumption of these substances along with co-occurring emotional disturbances. To understand this positive feedback loop, this review focuses on a specific population of hypothalamic peptide neurons expressing melanin-concentrating hormone (MCH), which are positively related to dopamine reward and project to forebrain areas that mediate this behavior. It also examines neurons expressing the peptide hypocretin/orexin (HCRT) that are anatomically and functionally linked to MCH neurons and the molecular systems within these peptide neurons that stimulate their development and ultimately affect behavior. This report first describes evidence in animals that exposure in adults and during adolescence to rewarding substances, such as the drugs alcohol, nicotine and cocaine and palatable fat-rich food, stimulates the expression of MCH as well as HCRT and their intracellular molecular systems. It also increases reward-seeking and emotional behavior, leading to excess consumption and abuse of these substances and neurological conditions, completing this positive feedback loop. Next, this review focuses on the model involving embryonic exposure to these rewarding substances. In addition to revealing a similar positive feedback circuit, this model greatly advances our understanding of the diverse changes that occur in these neuropeptide/molecular systems in the embryo and how they relate, perhaps causally, to the disturbances in behavior early in life that predict a later increased risk of developing substance use disorders. Studies using this model demonstrate in animals that embryonic exposure to these rewarding substances, in addition to stimulating the expression of peptide neurons, increases the intracellular molecular systems in neuroprogenitor cells that promote their development. It also alters the morphology, migration, location and neurochemical profile of the peptide neurons and causes them to develop aberrant neuronal projections to forebrain structures. Moreover, it produces disturbances in behavior at a young age, which are sex-dependent and occur in females more than in males, that can be directly linked to the neuropeptide/molecular changes in the embryo and predict the development of behavioral disorders later in life. These results supporting the close relationship between the brain and behavior are consistent with clinical studies, showing females to be more vulnerable than males to developing substance use disorders with co-occurring emotional conditions and female offspring to respond more adversely than male offspring to prenatal exposure to rewarding substances. It is concluded that the continued consumption of or exposure to rewarding substances at any stage of life can, through such peptide brain systems, significantly increase an individual’s vulnerability to developing neurological disorders such as substance use disorders, anxiety, depression, or cognitive impairments. Full article

Background/Objectives: Pediatric acquired demyelinating syndromes (ADSs) encompass a heterogeneous group of disorders, including multiple sclerosis (MS), MOG antibody-associated disease (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD), with distinct clinical trajectories and prognoses. While analyzed collectively at baseline to reflect real-world diagnostic uncertainty, outcome predictors were also examined according to final diagnosis. Identifying early predictors is crucial for optimizing long-term outcomes. Methods: We retrospectively analyzed 30 pediatric patients (mean onset age: 11.3 years) with ADSs. Clinical, radiological, CSF, antibody, and neurophysiological data were collected and analyzed alongside treatment strategies. Outcomes—EDSS scores, neuroradiological changes, and clinical status—were evaluated over a 3-year period. Results: Final diagnoses included MOGAD (36.6%), MS (33.3%), NMOSD (6.6%), ADEM (10%), and other ADSs (13.3%). At onset, ≥3 brain lesions were present in 76.7% of patients. Disease-modifying therapies (DMTs) were used in 37% and acute immunotherapy in 90%. EDSS progression was significantly associated with DMT use at multiple timepoints, with additional predictors including MRI lesion type, CSF findings, antibody status, and evoked potentials. At 3 years, neurocognitive function predicted clinical outcome. Conclusions: Early immunotherapy and baseline instrumental findings are key predictors of outcome in pediatric ADSs. MOGAD showed a more favorable course, while MS and NMOSD were associated with greater long-term disability. A comprehensive, early diagnostic approach is essential for improving prognosis. Full article

Background: Acute necrotising encephalopathy (ANE) is a rare and severe type of encephalopathy with bilateral symmetrical brain lesions, often following a viral prodrome. ANE type 1 (ANE1) is a disease subtype with a predisposing mutation in the gene encoding RAN binding protein 2 (RANBP2). Methods: We report a case of a 3-year-old girl with clinical symptoms of ANE and brain MRI findings suggesting ANE1, which was subsequently confirmed by genetic analysis. Results: MRI of the brain demonstrated symmetrical high T2/FLAIR signal changes in the lateral geniculate bodies, claustrum, ventromedial thalami, subthalamic nuclei, mamillary bodies, and brainstem, with partly corresponding diffusion restriction, as well as additional haemorrhagic changes in the lateral geniculate bodies on susceptibility weighted imaging. Genetic analysis revealed a heterozygous pathogenic variant of the RANBP2 gene. With immunosuppressive and supportive treatment, the patient fully recovered and was discharged after 10 days in the hospital with no residual symptoms. Conclusions: Recognition of the characteristic MRI findings in ANE1 can facilitate a timely diagnosis and enhance the clinical management of the patient and their relatives, especially given the high risk of disease recurrence. Full article

Background: Exposure to per- and polyfluoroalkyl substances (PFAS, including 7H-Perfluoro-4-methyl-3,6-dioxaoctanesulfonic acid (PFESA-BP2), perfluorooctanoic acid (PFOA), and hexafluoropropylene oxide (GenX), has been associated with liver dysfunction. While previous research has characterized PFAS-induced hepatic lipid alterations, their downstream effects on energy metabolism remain unclear. This study investigates metabolic alterations in the liver following PFAS exposure to identify mechanisms leading to hepatoxicity. Methods: We analyzed RNA sequencing datasets of mouse liver tissues exposed to PFAS to identify metabolic pathways influenced by the chemical toxicant. We integrated the transcriptome data with a mouse genome-scale metabolic model to perform in silico flux analysis and investigated reactions and genes associated with lipid and energy metabolism. Results: PFESA-BP2 exposure caused dose- and sex-dependent changes, including upregulation of fatty acid metabolism, β-oxidation, and cholesterol biosynthesis. On the contrary, triglycerides, sphingolipids, and glycerophospholipids metabolism were suppressed. Simulations from the integrated genome-scale metabolic models confirmed increased flux for mevalonate and lanosterol metabolism, supporting potential cholesterol accumulation. GenX and PFOA triggered strong PPARα-dependent responses, especially in β-oxidation and lipolysis, which were attenuated in PPARα^−/− mice. Mitochondrial fatty acid transport and acylcarnitine turnover were also disrupted, suggesting impaired mitochondrial dysfunction. Additional PFAS effects included perturbations in the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, and blood–brain barrier (BBB) function, pointing to broader systemic toxicity. Conclusions: Our findings highlight key metabolic signatures and suggest PFAS-mediated disruption of hepatic and possibly neurological functions. This study underscores the utility of genome-scale metabolic modeling as a powerful tool to interpret transcriptomic data and predict systemic metabolic outcomes of toxicant exposure. Full article