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Microglia promote neurodegeneration and hyperkatifeia during withdrawal and prolonged abstinence from binge alcohol.

Proinflammatory microglial polarization, neuronal death, and hyperkatifeia/negative affect during withdrawal are key features of alcohol use … in female mice. Thus, this identifies a direct role for microglia in the development of AUD-related neuropathology and behavioral dysfunction, implicating microglia as cellular targets for the prevention of AUD phenotypes.

[Assessment of developmental neurotoxicity of pharmaceuticals using zebrafish behavior].

Pharmaceuticals used for pregnant women must be safe for the babies while therapeutic to the mothers. To ensure the safety of drugs, developmental neurotoxicity should be evaluated although it is currently not a mandatory requirement in the US and Europe at the regulatory level. Organisation for Economic Co-operation and Development (OECD) has constituted the test guideline (TG426) to assess developmental neurotoxicity. TG426 requires various assessments using animals (assuming rats), including the brain weight, neuropathology, locomotion, sensorimotor function, and learning ability of dams fr…

An integrated view of the relationships between amyloid, tau, and inflammatory pathophysiology in Alzheimer's disease.

Alzheimer's disease (AD) research is a large and burgeoning field, where varied methodological approaches are providing multifaceted, but sometimes contradictory, views on the etiology and progression of pathology. The current review aims to summarize and integrate these findings to provide greater coherence to an increasingly splintered field. We provide an overview of the findings from each subfield (neuropathology, positron emission tomography imaging, fluid biomarkers, genetics, transcriptomics/proteomics), highlighting the strengths and weaknesses of each approach and, where possible, try…

Characterizing positive and negative quantitative susceptibility values in the cortex following mild traumatic brain injury: a depth- and curvature-based study.

Evidence has linked head trauma to increased risk factors for neuropathology, including mechanical deformation of the sulcal fundus and, later, perivascular accumulation of hyperphosphorylated tau adjacent to these spaces related to chronic traumatic encephalopathy. However, little is known about microstructural abnormalities and cellular dyshomeostasis in acute mild traumatic brain injury in humans, particularly in the cortex. To address this gap, we designed the first architectonically motivated quantitative susceptibility mapping study to assess regional patterns of net positive (iron-relat…

Stearoyl-CoA desaturase inhibition normalizes brain lipid saturation, α-synuclein homeostasis, and motor function in mutant Gba1-Parkinson mice.

Loss-of-function mutations in the GBA1 gene are a prevalent risk factor for Parkinson's disease (PD). Defining features are Lewy bodies that … ition normalized GCase maturation and dampened lysosomal and lipid-rich clustering, key features of neuropathology in GBA-PD. In conclusion, this study supports that brain MUFA metabolism links GBA1 genotype and WT αS homeostasis to downstream neuronal and behavioral impairments, identifying SCD as a therapeutic target for GBA-PD.

Multimodal Magnetic Resonance Imaging with Mild Repetitive Head Injury in Awake Rats: Modeling the Human Experience and Clinical Condition.

Mild repetitive head injury is a serious health problem with long-term negative consequences. Changes in brain neurobiology were assessed wi … an increase in gliosis in the thalamus, cerebellum, and hippocampus. This study shows a sequelae of neuropathology caused by mild repetitive head injury that is commonly observed in clinical practice using MRI in patients. As such, it may serve as a model for testing the efficacy of new therapeutics using any or all of the measures as biomarkers to assess drug e …

Comparing Neuroprotective Drug Efficacy in Rodent Neonatal Brain Injury Models.

BACKGROUND: A challenge in preclinical neonatal neuroprotection research is implementation of study designs that enable direct comparison of … s that induced inflammation, and some included post-HI brief moderate hypothermia. Sensorimotor and neuropathology measures were incorporated into a Composite Score that also accounted for deaths. Outcome was initially evaluated at P21 and in confirmatory studies at P35. A pre-specified Bayesian algorithm with futility and efficacy stopping rules was devised to …

Contribution of the dopaminergic system in toxoplasmic encephalitis neuroimmunopathogenesis.

Toxoplasma gondii (T. gondii), a parasitic intracellular protozoan, can establish a chronic infection in the host brain and cause significant neuropathology. The current study aimed to determine the role of Tyrosine Hydroxylase (TH), Dopamine Receptor D1 (D1R), Nuclear Receptor Related-1 (Nurr1), and Dopamine Transporter (DAT) expression in the neuroimmunopathogenesis of toxoplasmic encephalitis (TE) at 15, 30, 45, and 60 days after infection with T. gondii. Additionally, the study investigated whether there was a correlation between the markers on these critical days, which had yet to be expl…

Cerebellum mitochondrial DNA copy number is increased in Parkinson's disease.

Bioinformatics methods can be used to quantify mitochondrial DNA copy number from whole genome sequencing (WGS) data. We evaluated mitochond … t. Follow-on analyses of 128 Parkinson's Disease cerebellum samples and 33 controls that had paired neuropathology data and clinical scores demonstrated a significant increase in mitochondrial DNA copy number with Unified Staging System for Lewy Body disorders stages and Unified Parkinson's Disease Rating Scale (off meds) motor scores. Analysis of Lewy Body scor …

Heartbeat evoked potential and spectral analysis in patients with panic disorder during resting state.

Panic disorder (PD) involves recurrent panic attacks and anticipatory anxiety, with interoceptive dysfunction potentially contributing to it … (elevated beta oscillations) in PD. The study provides novel electrophysiological evidence for PD's neuropathology, identifying interoception-arousal dysregulation as a potential treatment target.

AAV-delivered PPT1 provides long-term neurological benefits in CLN1 mice and achieves therapeutic levels in sheep brain.

CLN1 disease is a fatal neurodegenerative condition caused by deficiency in palmitoyl-protein thioesterase 1 (PPT1), for which no disease-mo … rapeutic benefits, such as extended lifespan, preserved neurobehavioral function, and prevention of neuropathology, making treated Ppt1-/- mice nearly indistinguishable from wild type. A translatability study in healthy adult sheep, assessing biodistribution of therapeutic in a large and fully developed brain, showed widespread CNS transduction and PPT1 expressi …

Cognitive reserve is associated with education, social determinants, and cognitive outcomes among older American Indians in the Strong Heart Study.

Cognitive reserve, a component of resilience, may be conceptualized as the ability to overcome accumulating neuropathology and maintain healthy aging and function. However, research measuring and evaluating it in American Indians is needed. We recruited American Indians from 3 regional centers for longitudinal examinations (2010-13, n = 818; 2017-19, n = 403) including MRI, cognitive, clinical, and questionnaire data. We defined cognitive reserve by measuring the residual from individual regressions of cognitive tests over imaged brain volumes, adjusted for age and sex. Analyses examined three…

Neuronal Damage in Murine Experimental Cerebral Malaria, Implications for Neuronal Repair and Sequelae.

Cerebral malaria (CM) is a deadly complication of P. falciparum infection. Although adults with CM have a higher mortality rate, CM affects … s and attention deficit hyperactivity disorder, which can remain with the survivors. The underlying neuropathology of these post CM neurologic sequelae are unclear. Therefore, we probed the extensive neuronal damage that occurs in an experimental murine model of cerebral malaria (eCM), focusing on the hippocampus. In addition, we explored responses of neuro-prog …

Низкочастотное магнитное поле и нейродегенеративные заболевания: систематический обзор исследований животных.

Эпидемиологические исследования выявили связь между профессиональным воздействием низкочастотных магнитных полей и возникновением заболевания моторными нейронами и болезнью Альцгеймера. Не было обнаружено никакой связи с болезнью Паркинсона, и доказательств множественного склероза недостаточно. Модели животных, в которых изучается влияние низкочастотных магнитных полей на индукцию или прогрессирование нейродегенеративных заболеваний, могут дать больше доказательств причинно-следственной связи и основополагающих механизмов. Был проведен систематический поиск и обзор рецензируемых научных статей

Совпадение в аннотации оригинала
Epidemiological studies have found an association between occupational exposure to low frequency magnetic fields and the occurrence of motor … upport a causal relationship between exposure to low frequency magnetic fields and the induction of neuropathology relevant for Alzheimer's disease, but the number of studies relevant for motor neuron disease, multiple sclerosis and Parkinson's disease is too limited to draw conclusions. Secondly, experimental studies in existing animal models for neurodegenerat …

The role of the placenta-brain axis in psychoneuroimmune programming.

Gestational exposures have enduring impacts on brain and neuroimmune development and function. Perturbations of pregnancy leading to placent … hanisms may be a valuable approach for the prevention and mitigation of intergenerational, lifelong neuropathology.

Neural signatures of default mode network subsystems in first-episode, drug-naive patients with major depressive disorder after 6-week thought induction psychotherapy treatment.

Evidence indicates that the default mode network (DMN) plays a crucial role in the neuropathology of major depressive disorder (MDD). However, the neural signatures of DMN subsystems in MDD after low resistance Thought Induction Psychotherapy (TIP) remain incompletely understood. We collected functional magnetic resonance imaging data from 20 first-episode, drug-naive MDD and 20 healthy controls (HCs). The DMN was segmented into three subsystems and seed-based functional connectivity (FC) was computed. After 6-week treatment, the significantly reduced FCs with the medial temporal lobe memory s…

Radiation Therapy for Meningiomas - Where Do We Stand and What's on the Horizon?

Radiation therapy, including conventionally fractionated external beam radiation therapy, stereotactic radiosurgery, and fractionated stereotactic radiation therapy, is a cornerstone in the interdisciplinary management of meningiomas. Recent advances in radiation oncology and also in other fields, such as neuropathology and imaging, have various implications for meningioma radiation therapy. This review aims to summarize current and anticipated developments, as well as active clinical trials related to the use of radiation therapy for meningiomas. In imaging, positron emission tomography has p…

Prevalence, risk factors, and impact of anxiety in early Alzheimer disease: a retrospective study of an autopsy-confirmed cohort.

Anxiety is a neuropsychiatric symptom (NPS) of Alzheimer disease (AD) patients which has been studied primarily in prospective and retrospec … iopathy and arteriosclerosis on brain autopsy, but there were no such associations with concomitant neuropathology at MCI and mild dementia. Anxiety associated with increased progression rate (∼2.5-fold) from SCD to MCI/dementia stages, but not from MCI to dementia. These results suggest an important relationship between anxiety and AD, especially at the preclin …

Inhibitory CCK+ basket synapse defects in mouse models of dystroglycanopathy.

Dystroglycan (Dag1) is a transmembrane glycoprotein that links the extracellular matrix to the actin cytoskeleton. Mutations in Dag1 or the genes required for its glycosylation result in dystroglycanopathy, a type of congenital muscular dystrophy characterized by a wide range of phenotypes including muscle weakness, brain defects, and cognitive impairment. We investigated interneuron (IN) development, synaptic function, and associated seizure susceptibility in multiple mouse models that reflect the wide phenotypic range of dystroglycanopathy neuropathology. Mice that model severe dystroglycano…

Rodent Models of Alzheimer's Disease: Past Misconceptions and Future Prospects.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no effective treatments, not least due to the lack of authentic animal models. Typically, rodent models recapitulate the effects but not causes of AD, such as cholinergic neuron loss: lesioning of cholinergic neurons mimics the cognitive decline reminiscent of AD but not its neuropathology. Alternative models rely on the overexpression of genes associated with familial AD, such as amyloid precursor protein, or have genetically amplified expression of mutant tau. Yet transgenic rodent models poorly replicate the neuropatho…