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Memory network and cognitive reserve are associated with preserved and stimulated cholinergic neurotransmission.

The cholinergic system plays a central role in cognition and neural function, and, in Alzheimer disease (AD) and Lewy body disease (LBD), it … o account for the fact that individual clinical presentation might be milder than expected based on neuropathology. This mismatch can be explained by individual brain reserve (BR) buildup on life experiences, lifestyles, and neurobiologic factors that are associated with resilience. Sparse findings exist suggesting that the CR might result in an increased or pre …

Loss of the NF-κB negative regulator Pirk in Drosophila links brain and gut immunity to neurodegeneration.

A gut-brain axis influenced by host innate immunity and resident microbiota has been implicated in neurological conditions including Alzheim … of the relevant phenotypes suggesting a later contribution of the nervous system to the underlying neuropathology. Knockout of the antimicrobial peptide (AMP) gene AttacinD or rearing flies in axenic conditions recovered some of the neurological phenotypes, suggesting both chronic AMP gene expression as well as gut bacteria changes as mediators. Our results ind …

Microglia Promote Neurodegeneration and Hyperkatifeia during Withdrawal and 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.

Idebenone Mitigates Traumatic-Brain-Injury-Triggered Gene Expression Changes to Ephrin-A and Dopamine Signaling Pathways While Increasing Microglial Genes.

Traumatic brain injury (TBI) leads to persistent pro-inflammatory microglial activation implicated in neurodegeneration. Idebenone, a coenzyme Q10 analogue that interacts with both mitochondria and the tyrosine kinase adaptor SHC1, inhibits aspects of microglial activation in vitro. We used the NanoString Neuropathology Panel to test the hypothesis that idebenone post-treatment mitigates TBI-pathology-associated acute gene expression changes by moderating the pro-inflammatory microglial response to injury. Controlled cortical impact to adult male mice increased the microglial activation signat…

Functional characteristics of the frontal cortex during the verbal fluency task in subthreshold depression: A fNIRS study.

BACKGROUND: Subthreshold depression (SD), a recognized prodromal stage and major risk factor for major depressive disorder (MDD). Dysfunctio … Cp of the overall frontal cortex has the potential for prediction in SD. Our findings elucidate SD neuropathology and establish a foundation for early MDD diagnosis.

Astrocytopathy Is Associated with CA1 Synaptic Dysfunction in a Mouse Model of Down Syndrome.

Brain pathophysiology in Down syndrome (DS), the most common genetic cause of intellectual disability, has traditionally been considered a c … hin the hippocampus, suggesting localized vulnerability and complex glial involvement in DS-related neuropathology.

DYRK1A in the physiology and pathology of the neuron-astrocyte axis.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a dosage-sensitive kinase with critical roles in the neuron-astroc … ions DYRK1A as a potential bridge between DS and AD, mechanistically connecting gene overdosage and neuropathology in both conditions. However, research on DYRK1A pathophysiology has primarily centered on neurons, leaving astrocytes largely understudied. Considering the vital neuroprotective functions of astrocytes, broadening DYRK1A research to encompass these …

Immunotherapeutic Protection From a Soman Nerve Agent Model Compound.

Chemical warfare agents include potent nerve agents (NAs). NAs covalently inhibit cholinesterases (ChEs) in the blood and in the central nervous system of animals administered NAs. An example of a very toxic NA is soman. After administration to animals, NA-ChE inhibition results and causes acetylcholine (ACh) to build up in the synapse where ordinarily only small amounts of ACh are present. This stimulates autonomic receptors and blocks neuromuscular junction receptors, causes severe neurological side effects including seizures and neuropathology and can result in death by respiratory failure.…

Structural Neuroimaging Correlates of Neuropsychiatric Symptoms in Alzheimer's Disease: A Systematic Literature Review.

INTRODUCTION: Neuropsychiatric symptoms (NPS) such as increased apathy, affective symptoms, psychosis and hyperactivity are common in Alzheimer's disease (AD) and are associated with increased disease severity and caregiver burden. In contrast to well-characterized associations between AD-related cognitive deficits and focal neuropathology (e.g., memory and hippocampal atrophy), fewer studies have focused on associations between NPS-brain associations in AD. Furthermore, studies focusing on magnetic resonance imaging measures of gray matter (GM) abnormalities associated with NPS in AD have not…

SARS-CoV-2 (MA10) Infection Aggravates Cerebrovascular Pathology in Endothelial Nitric Oxide Synthase-Deficient Mice.

SARS-CoV-2 can cause neurological issues, including cognitive dysfunction in COVID-19 survivors. Endothelial dysfunction, a key mechanism in … -CoV-2-induced morbidity, neuroinflammation, and brain senescence, linking eNOS to COVID-19-related neuropathology.

Human Mutant Dynactin Subunit 1 Causes Profound Motor Neuron Disease Consistent with Possible Mechanisms Involving Axonopathy, Mitochondriopathy, Protein Nitration, and T-Cell-Mediated Cytolysis.

Mutations in the gene encoding the p150 subunit of the dynactin complex (DCTN1) are linked to amyotrophic lateral sclerosis, spinal and bulbar muscular atrophy, and Perry syndrome. These neurodegenerative diseases can cause muscle weakness and atrophy, parkinsonian-like symptoms, and paralysis. To examine the evolution of neuropathology caused by a mutation in DCTN1 and cellular mechanisms of disease for therapeutic discovery, we characterized mice expressing either human wildtype or mutant (G59S) DCTN1. Neuron-specific expression of mutant, but not wildtype, DCTN1 caused fatal age-related par…

Common and disorder-specific neural activity and connectivity in generalized anxiety, panic, and social anxiety disorders.

Understanding the distinct and shared neural mechanisms of generalized anxiety disorder, panic disorder, and social anxiety disorder could h … social anxiety symptom severity. These findings provide valuable implications for understanding the neuropathology, diagnosing, and developing targeted therapeutic interventions for different subtypes of anxiety disorders.

Удаление X-хромосомного гена Kdm6a в микроглии женских мышей улучшает нейроинфламмацию и восстанавливает транслатомные профили.

Женщины в большей степени подвержены множественным склерозам (МС), чем мужчины, при этом, согласно сообщениям, коэффициент заболеваемости составляет около 3:1. Kdm6a — X-хромосомный ген, который избегает инактивации X, что приводит к более высокому выражению гистонной деметилазы KDM6A у самок по сравнению с мужчинами. Здесь мы сосредоточили внимание на роли Kdm6a в микроглии в MS, потому что этот тип клеток играет ключевую роль в нейропатологии MS. Kdm6a был выборочно удален из микроглии в экспериментальной аутоиммунной энцефаломиелитной (EAE) мыши, установленной модели MS. Удаление Kdm6a в ми

Совпадение в аннотации оригинала
Women are more susceptible to multiple sclerosis (MS) than men, with a reported incidence ratio of ~3:1. Kdm6a is an X-chromosomal gene that … , we focused on the role of Kdm6a in microglia in MS because this cell type plays a key role in the neuropathology of MS. Kdm6a was selectively deleted from microglia in experimental autoimmune encephalomyelitis (EAE) mice, an established model of MS. Deletion of Kdm6a in microglia ameliorated pathology, reduced the expression of disease-associated markers, incr …

Условное исключение гена АТХN1 склерозной чувствительности указывает на клеточное воздействие в клеточном отсеке В.

Увеличение числа фактов подтверждает механистическая роль клеток B в патогенезе аутоиммунного расстройства, множественного склероза (MS). Ранее мы документально зафиксировали, что ген риска MS атаксин-1 (ATXN1) модифицирует ключевые функции B-клетки и серьезность экспериментального аутоиммунного энцефаломиелита (EAE). ATXN1 кодирует полиглутаминовый протеин атаксин-1, который работает в клеточном ядре в качестве кристалла транскрипции генов. Однако, учитывая повсеместное выражение белка атаксин-1 и ограничения глобальных моделей мыши Atxn1-null, точный вклад атаксина-1 в функционирование клето

Совпадение в аннотации оригинала
Increasing evidence supports a mechanistic role for B cells in the pathogenesis of the autoimmune disorder multiple sclerosis (MS). We previ … ase in response to encephalitogenic challenges, but it is insufficient to modify the trajectory and neuropathology of the EAE model. Altogether, these results pinpoint a complex regulatory role for ataxin-1 in autoimmune demyelination involving multiple cellular targets.

Akkermansia muciniphila Moduls Central Nervous System Autoimune Autoimune and Coginative Disability by Inhibiting Hippocampal NLRP3-Mediated Нейроинфламмация.

ЦЕЛЬ: Многочисленные исследования продемонстрировали важную роль " Akkermansia muciniphila " (A. muciniphila) в укреплении иммунной реакции принимающей страны и метаболических функций. Вместе с тем увеличение числа пациентов, страдающих множественным склерозом (МС), привело к тому, что акцент был сделан на связи между A. muciniphila и болезнями, при этом основные механизмы остаются неизвестными. МЕТОД: Для оценки степени обезвоживания и воспаления использовались растворохром цианин, пятно гематоксилин-эозина (H&E) и пятно иммунофторации. Изменения в микробиоте были изучены по секвени

Совпадение в аннотации оригинала
BACKGROUND: Numerous studies have demonstrated the significant role of Akkermansia muciniphila (A. muciniphila) in enhancing host immune res … ULTS: We found that treatment with an appropriate dose of A. muciniphila (5.0 × 107 CFU/mL) reduced neuropathology and disease severity in experimental autoimmune encephalomyelitis (EAE) mice. In addition, A. muciniphila supplementation increased the diversity and abundance of intestinal microbiota while decreasing the Firmicutes/Bacteroidetes ratio. Moreover, i …

Beneficial effects of miR-132/212 deficiency in the zQ175 mouse model of Huntington's disease.

Huntington's disease (HD) is a rare genetic neurodegenerative disorder caused by an expansion of CAG repeats in the Huntingtin (HTT) gene. One hypothesis suggests that the mutant HTT gene contributes to HD neuropathology through transcriptional dysregulation involving microRNAs (miRNAs). In particular, the miR-132/212 cluster is strongly diminished in the HD brain. This study explores the effects of miR-132/212 deficiency specifically in adult HD zQ175 mice. The absence of miR-132/212 did not impact body weight, body temperature, or survival rates. Surprisingly, miR-132/212 loss seemed to alle…

Endocrine Dyscrasia in the Etiology and Therapy of Alzheimer's Disease.

The increase in the incidence of dementia over the last century correlates strongly with the increases in post-reproductive lifespan during … nadal sex hormone production with menopause and andropause, appear central to the development of AD neuropathology and cognitive decline. This is supported by numerous cell biology, preclinical animal, and epidemiological studies, as well as human clinical studies where suppression of circulating luteinizing hormone and/or follicle-stimulating hormone with eithe …

Clinicopathological correlation of cerebrospinal fluid alpha-synuclein seed amplification assay in a behavioral neurology autopsy cohort.

INTRODUCTION: Lewy body disease (LBD) is a common primary or co-pathology in neurodegenerative syndromes. An alpha-synuclein seed amplification assay (αSyn-SAA) is clinically available, but clinical performance, especially lower sensitivity in amygdala-predominant cases, is not well understood. METHODS: Antemortem CSF from neuropathology-confirmed LBD cases was tested with αSyn-SAA (N = 56). Diagnostic performance and clinicopathological correlations were examined. RESULTS: Similar to prior reports, sensitivity was 100% for diffuse and transitional LBD (9/9), and overall specificity was 96.3…

Impact of motor dysfunction on neuropsychiatric symptom profile in patients with autopsy-confirmed Alzheimer's disease.

Motor dysfunction, which includes changes in gait, balance, and/or functional mobility, is a lesser-known feature of Alzheimer's Disease (AD … iated with a higher number and severity of NPS, which may be partially explained by comorbid non-AD neuropathology.

Selective dopaminergic neurotoxicity modulated by inherent cell-type specific neurobiology.

Parkinson's disease (PD) is a debilitating neurodegenerative disease affecting millions of individuals worldwide. Hallmark features of PD pa … ironment interaction. Mechanistic studies have identified a variety of chemical PD risk factors. PD neuropathology occurs throughout the brain and peripheral nervous system, but it is the loss of DAergic neurons in the SNpc that produce many of the cardinal motor symptoms. Toxicology studies have found specifically the DAergic neuron population of the SNpc exhib …