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Expression of Transcripts Selective for GABA Neuron Subpopulations across the Cortical Visuospatial Working Memory Network in the Healthy State and Schizophrenia.

Visuospatial working memory (WM), which is impaired in schizophrenia, depends on a distributed network including visual, posterior parietal, and dorsolateral prefrontal cortical regions. Within each region, information processing is differentially regulated by subsets of γ-aminobutyric acid (GABA) neurons that express parvalbumin (PV), somatostatin (SST), or vasoactive intestinal peptide (VIP). In schizophrenia, WM impairments have been associated with alterations of PV and SST neurons in the dorsolateral prefrontal cortex. Here, we quantified transcripts selectively expressed in GABA neuron s

Dysregulation of REV-ERBα impairs GABAergic function and promotes epileptic seizures in preclinical models.

To design potentially more effective therapies, we need to further understand the mechanisms underlying epilepsy. Here, we uncover the role of Rev-erbα in circadian regulation of epileptic seizures. We first show up-regulation of REV-ERBα/Rev-erbα in brain tissues from patients with epilepsy and a mouse model. Ablation or pharmacological modulation of Rev-erbα in mice decreases the susceptibility to acute and chronic seizures, and abolishes diurnal rhythmicity in seizure severity, whereas activation of Rev-erbα increases the animal susceptibility. Rev-erbα ablation or antagonism also leads to

[Prevention and treatment of tardive dyskinesia caused by antipsychotic drugs].

INTRODUCTION: Tardive dyskinesia (TD) is a movement disorder of tongue, jawbone, trunk and/or limbs that may appear after a prolonged use of dopamine receptor blocking agents (after 3 months of treatment or after 1 month for patients over 60), and that are present during at least four consecutive weeks. TD is a frequent side effect of both classical neuroleptics and new generation antipsychotic drugs. The prevalence of iatrogenic TD is between 24 and 32 % after treatment with classical neuroleptics and about 13 % after treatment with a new generation antipsychotic. OBJECTIVE: This paper prese

Neuroendocrine mechanisms during reversible hypovolaemic shock in humans with emphasis on the histaminergic and serotonergic system.

In humans, the head-up tilted position results in central hypovolaemia which mimicks haemorrhage and is associated with cardiovascular changes that can be divided into two stages. 1) One stage with increase in HR and vascular resistance and a slight increase in MAP. 2) Another stage with decrease in HR, vascular resistance and MAP and appearance of presyncopal symptoms (hypovolaemic shock). The first stage is "sympathoexcitatory" as plasma NA originating from postganglionic vasoconstrictory sympathetic neurons increase. Limb vascular resistance contributes to the increase in TPR at this time.

Therapies in Stiff-Person Syndrome: Advances and Future Prospects Based on Disease Pathophysiology.

Among the glutamic acid decarboxylase (GAD)-antibody-spectrum disorders, the most common phenotypic subset is the stiff-person syndrome (SPS), caused by impaired GABAergic inhibitory neurotransmission and autoimmunity characterized by very high titers of GAD antibodies and increased GAD-IgG intrathecal synthesis. If not properly treated or untreated because of delayed diagnosis, SPS progresses leading to disability; it is therefore fundamental to apply the best therapeutic schemes from the outset. This article is focused on the rationale of specific therapeutic strategies based on the SPS path

An update on malignant tumor-related stiff person syndrome spectrum disorders: clinical mechanism, treatment, and outcomes.

Stiff person syndrome (SPS) is a rare central nervous system disorder associated with malignancies. In this review, we retrieved information from PubMed, up until August 2023, using various search terms and their combinations, including SPS, stiff person syndrome spectrum disorders (SPSSDs), paraneoplastic, cancer, and malignant tumor. Data from peer-reviewed journals printed in English were organized to explain the possible relationships between different carcinomas and SPSSD subtypes, as well as related autoantigens. From literature searching, it was revealed that breast cancer was the most

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… Decreased GABAergic activity is the major physiopathological mechanism of SPSSD GABAergic neurons are responsible for inhibitory signals in the CNS and express high levels of GAD65. … Therefore, drugs targeting GABAergic neurons can be effective in treating SPSSD; by inhibiting the attack on GAD, GABA levels are reduced ( 168 ). 6.1.1. Benzodiazepines Benzodiazepines are the first-line treatment for patients with SPS. …

Роль микроглии в синаптогенезе, синаптической и синаптической пластичности в физиологических условиях и в нарушениях центральной нервной системы.

Микроглии являются постоянными иммунными клетками мозга, которые были широко изучены для их иммунного наблюдения и фагоцитоза. В последние годы постепенно признается важная роль микроглии в синапсовом образовании, ликвидации и пластичности. Синапсы являются основным режимом связи между нейронами. Они постоянно меняются в количестве и пластичности на протяжении всего жизненного цикла, который является основой обучения и памяти. Микроглии являются сильно мотилированными, ветковыми формами, которые осуществляют мониторинг микроокружающей среды центральной нервной системы (КНС) и поощряют синапсов

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… Microglia preferentially phagocytose GABAergic neurons in epilepsy. [ 6 , 333 , 339 , 340 ] The role of microglia on synapses in CNS diseases. … All C1q-positive neurons in normal aging are GABAergic neurons; therefore, it was hypothesized that C1q released by microglia first accumulates in GABAergic neurons, thereby contributing to the loss of inhibitory neurons [ 339 , 340 ]. …

The influence of neuro-tumor interactions on tumorigenesis and therapeutic response.

The intricate crosstalk between the nervous system and tumors has emerged as a pivotal determinant of tumorigenesis, progression, and therapeutic response. This review synthesizes current insights into neuro-tumor interactions, highlighting how neuronal networks within the tumor microenvironment (TME) modulate cancer cell proliferation, invasion, and angiogenesis by releasing neurotransmitters, growth factors, etc. The neuro-immune axis, a critical interface linking neural signaling to immune regulation, is explored in depth, elucidating how neuronal-derived molecules influence the phenotype a

Ionic Plasticity: Common Mechanistic Underpinnings of Pathology in Spinal Cord Injury and the Brain.

The neurotransmitter GABA is normally characterized as having an inhibitory effect on neural activity in the adult central nervous system (CNS), which quells over-excitation and limits neural plasticity. Spinal cord injury (SCI) can bring about a modification that weakens the inhibitory effect of GABA in the central gray caudal to injury. This change is linked to the downregulation of the potassium/chloride cotransporter (KCC2) and the consequent rise in intracellular Cl- in the postsynaptic neuron. As the intracellular concentration increases, the inward flow of Cl- through an ionotropic GABA

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… Several cellular processes can influence the degree to which engaging a GABAergic neuron affects post-synaptic neural activity, including the subunit structure of the GABA-A receptor and the trafficking of GABARs [ 9 ]. … As a consequence, engaging GABAergic neurons that presynaptically innervate a sensory neuron after it enters the spinal cord does not cause an influx of Cl − (Sorkin et al., 2018). …

Нейроатомные корреляции пузырьков наполняют: активация симметрии оценки мета-анализа функциональных исследований в области нейронизации.

Ужасная континуальность зависит от сложного взаимодействия между хранением мочи и дезертирством с участием как спинных рефлексов, так и сверхспинных участков мозга для координации добровольного контроля за опорожнением. Несмотря на большое число исследований в области патофизиологии нейрогенного мочевого пузыря и его недержание, меньше известно о центральных корреляциях заполнения мочевого пузыря. Metods ALE (оценка вероятности активации) метаанализа, включая общее число 14 исследования 243 Участники в различных условиях заполнения мочевого пузыря в ходе функционального нейроимации были продем

Association of stiff-person syndrome with autoimmune endocrine diseases.

BackgroundStiff-person syndrome (SPS) and its subtype, stiff limb syndrome (SLS), are rare neurological disorders characterized by progressive muscular rigidity and spasms. Glutamic acid decarboxylase (GAD) is the enzyme that catalyzes the production of γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter of the central nervous system. SPS is an autoimmune disease triggered by anti-glutamic acid decarboxylase antibody (anti-GAD Ab). Clinically, anti-GAD Ab is associated with SPS, type 1 diabetes mellitus (T1DM), and other autoimmune diseases.AimTo investigate the link of autoimmune

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… Anti-GAD Ab is highly directed against GABAergic neurons, making it a useful marker for diagnosis of insulin-dependent diabetes mellitus, epilepsy, and SPS[ 1 ]. Another antibody to γ-aminobutyric acid receptor-associated protein (anti-GABARAP Ab) was first linked to SPS by Raju in 2006[ 2 ]. …

Pruritus: an overview. What drives people to scratch an itch?

Pruritus is a common complaint associated with many conditions. It negatively impacts sleep, quality of life, and mortality. Itch is transmitted along both histaminergic and non-histaminergic pathways with a complex interplay between keratinocytes, immune cells and cutaneous neurons. Individuals who present with pruritus should undergo a thorough assessment, especially those over 65 years old, to exclude underlying malignancy. Treatment no longer consists of antihistamines alone. Physicians now have an array of therapies in their armamentarium, to help alleviate this distressing symptom.

Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA-mRNA Interaction Involvement.

Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA-mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viabi

Ligand-Gated Ion Channels as Targets for Treatment and Management of Cancers.

Ligand-gated ion channels are an ionotropic receptor subtype characterized by the binding of an extracellular ligand, followed by the transient passage of ions through a transmembrane pore. Ligand-gated ion channels are commonly subcategorized into three superfamilies: purinoreceptors, glutamate receptors, and Cys-loop receptors. This classification is based on the differing topographical morphology of the receptors, which in turn confers functional differences. Ligand-gated ion channels have a diverse spatial and temporal expression which implicate them in key cellular processes. Given that t

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… Transcript levels of GAD are thus frequently used as a proxy for the identification of GABAergic neurons. The action of GABA is abrogated by its metabolism by GABA transaminase ( Olsen and DeLorey, 1999 ; Young and Bordey, 2009 ). … Neman et al. (2014) showed that breast-to-brain metastatic cells displayed increased GABA metabolism and a strong association between HER2 and reelin, a protein expressed by GABAergic neurons, implicating this phenotype with control over cell motility and cytoskeletal shape. …

Пересадка глиальных клеток человека в муринные мозги: систематический обзор эффективности и безопасности в нейродегенеративных расстройствах.

Справочная информация: Нейродегенеративные заболевания затрагивают миллионы людей во всем мире. С годами исследования мозга были сосредоточены главным образом на нейронах, но сейчас внимание перемещается на глиальные клетки, вспомогательные клетки мозга, которые играют жизненно важную роль в нейродегенеративных расстройствах. Таким образом, трансплантация глиальных клеток представляет собой новаторский подход к лечению различных нейродегенеративных расстройств, способных восстановить нейронную функцию. Мы провели оценку терапевтической эффективности трансплантации человеческих глиальных клеток

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… GDAs BMP transplantation rescues both dopaminergic neurons and parvalbumin-expressing GABAergic neurons, which are typically lost in PD. 31 Furthermore, Song et al. used co-grafted astrocytes particularly cultured from the ventral midbrain engineered with transcription factors Nurr1 and Foxa2 to investigate … Dopaminergic neurons and parvalbumin-expressing GABAergic neurons, which are destroyed in PD, are both uniquely restored by this one therapy strategy. …

Neurotropin alleviates rat osteocarcinoma pain via P2X3 receptor activation in the midbrain periaqueductal gray.

ObjectivesClinically effective analgesia treatment for patients afflicted with osteocarcinoma lessens the intensity of pain. The midbrain periaqueductal gray (PAG) plays a critical role in pain modulation, and activation of P2X3 receptors in this region mediates pain processing. Neurotropin is a small molecule drug used for analgesic treatment of a number of chronic pain conditions. The present study aims at determining whether P2X3 receptor activation in PAG is responsible for the analgesic effect of neurotropin in rats with osteocarcinoma pain.Materials and methodsThe tibia of female Sprague

Нацеливание на природные полифенолы антиоксидантов в целях защиты от нейроинфламмации и нейродегенеративных заболеваний: всеобъемлющий обзор.

Полифенолы, природные фитонутриенты, встречающиеся в растительных продуктах питания, привлекли значительное внимание к их потенциальному терапевтическому воздействию в неврологических заболеваниях и нейроинфламмации. Эти соединения обладают различными возможностями нейрозащиты, включая антиоксидантные, антивоспалительные и антиамильоидные свойства, которые способствуют смягчению развития таких нейродегенеративных заболеваний, как болезнь Альцгеймера (AD), болезнь Паркинсона (PD), деменция, множественный склероз (MS), Строк и болезнь Хантингтона (HD). Полифенолы были тщательно изучены на предме

Воздействие лечения на стероидом у женщин с множественным склерозом.

Множественный склероз (MS) — хроническое воспалительное нейродегенеративное заболевание центральной нервной системы. Происхождение MS связано с стероидными изменениями во время менструального цикла и беременности. Поскольку данных о воздействии лечения противомоскитных препаратов на стероидом недостаточно, мы провели оценку стерейдомичных изменений (79 стероидов) у 61 женщины-психолога репродуктивного возраста 39 лет (29, 47 лет) после лечения с помощью антимиосных препаратов на платформе GC-MS/MS и иммуномассы (кортизол и эстрадиол). Эти изменения были оценены с использованием уровней стероид

Cannabinoids: an Effective Treatment for Chemotherapy-Induced Peripheral Neurotoxicity?

Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the most frequent side effects of antineoplastic treatment, particularly of lung, breast, prostate, gastrointestinal, and germinal cancers, as well as of different forms of leukemia, lymphoma, and multiple myeloma. Currently, no effective therapies are available for CIPN prevention, and symptomatic treatment is frequently ineffective; thus, several clinical trials are addressing this unmet clinical need. Among possible pharmacological treatments of CIPN, modulation of the endocannabinoid system might be particularly promising, espe

АКНП 60th Ежегодное совещание: выдержки из плакатов P276 - P550.

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