Neurochemical Research最新文献

{"title":"GsMTx4 Combined with Exercise Exerts Neuroprotective Effects by Regulating Neuronal Autophagy in Rats with Spinal Cord Injury","authors":"Qianxi Li,&nbsp;Chenyu Li,&nbsp;Xinyan Li,&nbsp;Xinyu Liu,&nbsp;Jinghua Qian,&nbsp;Jianjun Li,&nbsp;Xuemei Li,&nbsp;Xin Zhang","doi":"10.1007/s11064-024-04304-8","DOIUrl":"10.1007/s11064-024-04304-8","url":null,"abstract":"<div><p>A sharp increase in intramedullary pressure after spinal cord injury (SCI) can aggravate secondary injury and lead to severe neurological deficits. Unfortunately, effective treatment options are currently lacking. The mechanosensitive ion channel Piezo1 plays an important role in the pathological process of SCI by transducing mechanical stress. The Piezo1 inhibitor GsMTx4 has been shown to have neuroprotective effects and may hold therapeutic potential for SCI. Given that single drug treatment strategy has limited effect on functional recovery after SCI, we explored the efficacy of combining GsMTx4 with exercise training in treating SCI in rats and investigated the underlying mechanisms. We used the T10 SCI rat model, administered GsMTx4 immediately after injury, and performed 4 weeks of body weight supported treadmill training starting (BWSTT) 2 weeks post injury. Subsequently, HE and LFB staining were used to observe the morphology of spinal cord tissue, WB was used to detect autophagy and apoptosis-related proteins, biochemical detection of calcium ion concentration and CTSD activity, IHC detection of LAMP1 expression, immunofluorescence labeling of NeuN and ChAT-positive motor neurons, as well as MBP and GFAP, and BBB scores were used to evaluate rat motor function. We found that the combined treatment of GsMTx4 drug and exercise training was more effective than single treatment alone. The combined treatment reduced calcium ion concentration, improved lysosomal function, enhanced autophagic flux, reduced cell apoptosis, and significantly improved the motor function of rats. This combined treatment regimen may pave the way for developing more comprehensive treatment strategies for SCI in the future.</p><h3>Graphical Abstract</h3><p><b>Mechanism diagram</b>. Piezo1 inhibitors combined with exercise exerts neuroprotective effects by regulating neuronal autophagy. Excessive mechanical stress following spinal cord injury (SCI) over activates the mechanosensitive Piezo1 channel in spinal neurons, leading to increased Ca²⁺ release and subsequent lysosomal dysfunction. This dysfunction decreases autophagic flux, potentially resulting in neuronal apoptosis, exacerbated glial scar formation, and demyelination. The application of Piezo1 inhibitors improves lysosomal function and enhances autophagic flux, thereby reducing cell apoptosis. Additionally, exercise training further amplifies the neuroprotective effects of Piezo1 inhibitors, contributing to overall neuronal recovery.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Assessment of Nutraceutical (Betanin) in Neuroblastoma Cell Line SHSY-5Y: An in-Vitro and in-Silico Approach","authors":"Kiruthiga Natarajan,&nbsp;Rajkuberan Chandrasekaran,&nbsp;Rajamanikandan Sundararaj,&nbsp;John Joseph,&nbsp;Kalaiselvi Asaithambi","doi":"10.1007/s11064-024-04312-8","DOIUrl":"10.1007/s11064-024-04312-8","url":null,"abstract":"<div><p>The cognitive dysfunction in the brain cause severe pathological consequences such as Alzheimer’s disease (AD), Parkinson’s disease. The current treatments are cost expensive and also cause negative side effects. Therefore it is inevitable to develop natural phyto-compounds as a drug like molecules to treat neurodegenerative diseases. In this context, we have assayed the neuroprotective effects of betanin, an indole derivative, in the neuroblastoma cell line SHSY-5Y cells. The neuroprotective effect was investigated in the β-amyloid (Aβ) - induced SHSY-5Y cells; betanin (25 µg) protected the SHSY-5Y cells from the toxic effects and maintained the cell viability. Moreover, the acridine orange and ethidum Bromide staining decipher that treatment of betanin in the Aβ-induced SHSY-5Y cells maintain the cell viablity sustainably. The Reactive Oxygen Species (ROS) assay infers that betanin quenches the generation of free radicals progressively in the Aβ-induced SHSY-5Y cells. In addition, the autophagy determination by flow cytometry revealed that betanin induces autophagy to remove the neurodegenerated cells. Further, we examined the docking and simulation patterns with the angiotensin-converting enzyme (ACE), TNF-α converting enzyme (TACE), glycogen synthase kinase 3 (GK3), and acetylcholinesterase enzymes (AChE) and amyloid precursor protein (APP). The <i>insilico</i> docking analysis denotes that betanin had a significant docking score with the target molecules. Thus, from the <i>invitro</i> and <i>insilico</i> studies, betanin strongly inhibit the toxic effects of Aβand protect the cells from degeneration.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiological and Pathological Role of mTOR Signaling in Astrocytes","authors":"Luise Hochmuth,&nbsp;Johannes Hirrlinger","doi":"10.1007/s11064-024-04306-6","DOIUrl":"10.1007/s11064-024-04306-6","url":null,"abstract":"<div><p>The mammalian target of rapamycin (mTOR) signaling pathway is one of the key regulators of cellular energy metabolism. It senses diverse alterations in the extracellular environment such as availability of nutrients and growth factors, and mediates the corresponding intracellular response. In the brain, astrocytes crucially contribute to energy and neurotransmitter metabolism, and numerous other functions. However, the relevance of physiological, astrocytic mTOR signaling in maintaining brain homeostasis and function is not well understood. Pathophysiological mTOR signaling is involved in manifold diseases in the central nervous system and most of the knowledge about astrocytic mTOR signaling has been derived from observations on these disorders. Dysregulation of the mTOR signaling pathway impairs important functions of astrocytes including neurotransmitter uptake and -signaling as well as energy metabolism. Some of these alterations could trigger neuropathological conditions such as epilepsy. This review focuses on how mTOR signaling regulates properties of astrocytes, and how these signaling events might contribute to the physiological function of the brain.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-024-04306-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiparametric Chemical Exchange Saturation Transfer MRI Detects Metabolic Changes in Mild Cognitive Impairment Cases at 3.0 Tesla","authors":"Dongyong Zhu,&nbsp;Xiaona Fu,&nbsp;Jia Liu,&nbsp;Xiaoming Liu,&nbsp;Lan Cheng,&nbsp;Xinli Zhang,&nbsp;Jue Lu,&nbsp;Qian Qin,&nbsp;Peng Sun,&nbsp;Zhenyu Zhou,&nbsp;Yiming Feng,&nbsp;Jing Wang","doi":"10.1007/s11064-024-04307-5","DOIUrl":"10.1007/s11064-024-04307-5","url":null,"abstract":"<div><p>This study aimed to assess the potential of multiparametric chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) for MCI detection. Twenty-eight patients with MCI and 31 age- and gender-matched normal controls (NCs) were enrolled. CEST MRI was performed with a gradient and spin-echo sequence on a 3T scanner. Multi-parametric CEST parameters were analyzed, such as amide CEST, amine CEST, amine and amide concentration independent assay (AACID), magnetization transfer ratio yielding rex (MTR_rex-amide), and downfield rNOE suppressed apparent exchange-dependent relaxation amide proton (DNS-AREX-amide). Statistical analyses of CEST parameters were performed to evaluate group differences, their correlations with Montreal cognitive assessment (MoCA) score, and diagnostic performance for MCI. Compared with NC group, amide CEST as well as MTR_rex-amide decreased in the left hippocampus and amine CEST as well as AACID increased in the right hippocampus in the MCI group; In both hippocampi, the DNS-AREX-amide were significantly lower in the MCI group versus the NC group (all <i>P</i> &lt; 0.05). Amine CEST in the right hippocampus was negatively correlated with MoCA score (<i>r</i> = − 0.457, <i>p</i> = 0.017); DNS-AREX-amide in the bilateral hippocampus was positively correlated with MoCA score (left: <i>r</i> = 0.449, <i>P</i> = 0.019; right: AUC = 0.529, <i>P</i> = 0.05). DNS-AREX-amide in the bilateral hippocampus have a good ability to identify MCI (left: AUC = 0.756, <i>P</i> &lt; 0.01; right: AUC = 0.762, <i>P</i> &lt; 0.01). CEST MRI provides a potential imaging diagnostic strategy for MCI, which may promote early detection of MCI and provide novel insights into the pathological progress toward AD.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Effects of STAT3 Inhibitor on Hydrogen Peroxide-Induced Neuronal Cell Death via the ERK/CREB Signaling Pathway","authors":"Seul-Ki Kim,&nbsp;Yong-Jin Kwon,&nbsp;Eun-Bi Seo,&nbsp;Hyun-Seung Lee,&nbsp;Jie Ohn Sohn,&nbsp;Hyun Mu Shin,&nbsp;Sung Joon Kim,&nbsp;Sang-Kyu Ye","doi":"10.1007/s11064-024-04252-3","DOIUrl":"10.1007/s11064-024-04252-3","url":null,"abstract":"<div><p>This study investigates the neuroprotective potential of STAT3 inhibition in reducing oxidative stress-induced neuronal damage and apoptosis, a major factor contributing to the onset and progression of neurodegenerative diseases, including Alzheimer’s disease (AD). Our findings demonstrate that STAT3 inhibitors significantly enhance cell survival and reduce apoptosis in SH-SY5Y cells exposed to hydrogen peroxide. These protective effects are mediated through the ERK/CREB signaling pathway rather than direct suppression of STAT3 phosphorylation. Further analysis revealed that the ERK pathway is a critical mediator of CREB activation following STAT3 inhibition. The protective effects of STAT3 inhibitors were significantly reduced in the presence of the ERK inhibitor PD98059, underscoring the importance of the ERK/CREB axis in neuroprotection. We observed that STAT3 inhibitors promote CREB phosphorylation, leading to the upregulation of immediate early genes such as c-Fos, c-Jun, Arc, Egr-1, NR4A1, and Homer1a, as well as BDNF. These genes are crucial for synaptic plasticity and long-term memory formation, suggesting that STAT3 inhibition may ameliorate cognitive impairments in neurodegenerative conditions. Our results highlight the potential of STAT3 inhibitors to counteract oxidative stress and enhance cognitive functions by modulating the ERK/CREB signaling pathway. These findings provide valuable insights into the molecular mechanisms of STAT3 inhibition and support its therapeutic potential for treating neurodegenerative diseases.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-024-04252-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Neural Circuits in Cognitive Impairment","authors":"Li Zhang,&nbsp;Guodong Liu,&nbsp;Yaonan Peng,&nbsp;Jinqi Gao,&nbsp;Mi Tian","doi":"10.1007/s11064-024-04309-3","DOIUrl":"10.1007/s11064-024-04309-3","url":null,"abstract":"<div><p>Cognitive impairment refers to abnormalities in learning, memory and cognitive judgment, mainly manifested as symptoms such as decreased memory, impaired orientation and reduced computational ability. As the fundamental unit of information processing in the brain, neural circuits have recently attracted great attention due to their functions in regulating pain, emotion and behavior. Furthermore, a growing number of studies have suggested that neural circuits play an important role in cognitive impairment. Neural circuits can affect perception, attention and decision-making, they can also regulate language skill, thinking and memory. Pathological conditions crucially affecting the integrity and preservation of neural circuits and their connectivity will heavily impact cognitive abilities. Nowadays, technological developments have led to many novel methods for studying neural circuits, such as brain imaging, optogenetic techniques, and chemical genetics approaches. Therefore, neural circuits show great promise as a potential target in mitigating cognitive impairment. In this review we discuss the pathogenesis of cognitive impairment and the regulation and detection of neural circuits, thus highlighting the role of neural circuits in cognitive impairment. Hence, therapeutic agents against cognitive impairment may be developed that target neural circuits important in cognition.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Potential of Aminonaphthoquinone Derivatives Against Amyloid Beta-Induced Neuronal Cell Death Through Modulation of SIRT1 and BACE1","authors":"Setthawut Apiraksattayakul,&nbsp;Ratchanok Pingaew,&nbsp;Veda Prachayasittikul,&nbsp;Waralee Ruankham,&nbsp;Tanawut Tantimongcolwat,&nbsp;Virapong Prachayasittikul,&nbsp;Supaluk Prachayasittikul,&nbsp;Kamonrat Phopin","doi":"10.1007/s11064-024-04281-y","DOIUrl":"10.1007/s11064-024-04281-y","url":null,"abstract":"<div><p>Alzheimer’s disease (AD) is characterized by the accumulation of tau protein tangles and amyloid-β (Aβ) plaques in the central nervous system (CNS), leading to progressive neurodegeneration. Hence, the discovery of disease-modifying agents capable of delaying the progression is essential for effective management. Aminonaphthoquinone (ANQ) is an attractive pharmacophore with various biological effects. This study explores the neuroprotective potentials of ANQ derivatives (<b>1</b>–<b>18</b>) using in vitro models of AD pathology (i.e., Aβ₄₂-induced SH-SY5Y cells). Findings demonstrated that all compounds mitigated Aβ₄₂-induced cellular damage by preserving cell viability and morphology. Among all, four compounds (<b>10</b>, <b>12</b>, <b>16</b>, and <b>18</b>) showed potent antioxidant activities as well as abilities to minimize AD-related damages (i.e. decreasing intracellular reactive oxygen species (ROS) production, preserving mitochondrial membrane potential (MMP), protecting membrane damage, and modulating beta-secretase 1 (BACE1) activity) with comparable protective effects to the well-known neuroprotectant, resveratrol (RSV). A molecular docking study indicated these compounds could suitably bind to sirtuin 1 (SIRT1) protein with preferable affinity. Key amino acid residues and key functional groups essential for binding interactions were revealed. Target prediction identified a list of possible AD-related targets of these compounds offering insights into their mechanisms of action and suggesting their multifunctional potentials. Additionally, in silico predictions revealed that these candidates showed favorable drug-like properties. Overall, this study highlighted the therapeutic potential of ANQ derivatives in AD treatment, emphasizing the need for further experimental validation and comprehensive investigations to fully realize their therapeutic benefits.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-024-04281-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring New and Promising Genetic Biomarkers for Evaluating Traumatic Brain Injuries: A Case-Control Study","authors":"Yasmin Kamal Abd Rabou,&nbsp;Abeer Ahmed Zayed,&nbsp;Sally A. Fahim,&nbsp;Marwa Abdelgwad,&nbsp;Ahmed El Fiki,&nbsp;Nermin Nabil Fayed","doi":"10.1007/s11064-024-04292-9","DOIUrl":"10.1007/s11064-024-04292-9","url":null,"abstract":"<div><p>Traumatic brain injury (TBI) is a common cause of morbidity and death in all age groups, with an estimated 50 million people having brain injury due to trauma each year. Accurate blood-based biomarkers are needed to assist with diagnosis of patients across the spectrum of time and severity. Our objectives were to explore the diagnostic precision of time- and severity- related four blood-based biomarkers: AKT3, GSK-3β, hsa-miR-16-5p, and MALAT-1 for TBI for the purpose of diagnosis, prognosis, and follow-up. 40 samples were recruited as the following: 30 TBI patients and 10 healthy volunteers as controls with matched age and sex. They were divided according to the Glasgow Coma Scale into mild (mTBI), moderate (modTBI), and severe(sTBI) TBI. Blood samples were withdrawn at entry, and after 5 and 30 days, RT-PCR was used for measuring the expression level. The results showed upregulated expression levels of AKT3, hsa-miR-16-5p and significantly downregulated expression levels of GSK-3β in TBI patients compared to controls at all timings measured. mTBI patients showed a higher expression level of hsa-miR-16-5p compared with modTBI, and sTBI patients. MALAT-1 level showed a significant increase in severe cases only. We concluded that AKT3, hsa-miR-16-5p, and GSK-3β are excellent diagnostic biomarkers in TBI patients at initial assessment, as well as at 5 and 30 days following the injury. Moreover, MALAT-1 had good diagnostic value in sTBI patients, and its prognostic value extends to 30 days. GSK-3β was an excellent biomarker for detecting mTBI.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s11064-024-04292-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Nuclear Peripheral Chromatin Lamin LMNB1 Gene in the Proliferation and Migration of Glioma Cells","authors":"Xiang-Cheng Shi,&nbsp;Ting Zhang,&nbsp;Cheng Li,&nbsp;Chen-Jia Guo,&nbsp;Qin Yang,&nbsp;Yao Feng,&nbsp;Jie Wang,&nbsp;Chong-Xiao Qu","doi":"10.1007/s11064-024-04298-3","DOIUrl":"10.1007/s11064-024-04298-3","url":null,"abstract":"<div><p>The goal of this study is to explore the role of the LMNB1 gene in glioma. A cohort of 160 patients who underwent glioma surgery were randomly selected of this study. The LMNB1 expression was assessed employing immunohistochemical and real-time quantitative polymerase chain reaction methods. Initially, RNA interference technology was applied to suppress gene expression, followed by the evaluation of tumor cell proliferation, apoptosis, cell cycle dynamics, and migration. The underlying molecular mechanisms of LMNB1 function were examined by a human phospho-kinase array and immunoblotting. And we established the xenograft models to determine the effect of tumor growth as well as the degree of invasion in shLMNB1 mice. Elevated LMNB1 expression correlated with unfavorable overall survival and disease-free survival. A substantial inhibition in cell growth was observed subsequent to LMNB1 knockdown in SHG-44 and U251 glioma cells. SHG-44-shLMNB1 cells exhibited a reduction in the S phase population, along with an increase in cells in G1 and G2 phases. Similarly, shLMNB1 U251 cells showed fewer cells in the S phase and an elevation in cells in G1 phase. Notably, increased apoptosis was observed in U251-shLMNB1 cells and SHG-44-shLMNB1 cells. Wound healing and Transwell migration assays demonstrated a significant decrease in the migration rate of both SHG-44-shLMNB1 and U251-shLMNB1 cells. The phosphorylation levels of Akt1/2/3, as well as the expressions of PI3K, AKT, and p-AKT proteins, were reduced in the shLMNB1 group. Downregulation of LMNB1 repressed tumor progress in vivo. The silencing of LMNB1 was found to significantly reduce the proliferation of human glioma cells, induce apoptosis in tumor cells, impede the progression of the cell cycle, and inhibit the migration of tumor cells. Consequently, we hypothesize that LMNB1 promotes glioma cell proliferation through mechanisms involving the inhibition of tumor cell apoptosis, acceleration of the cell cycle, and enhancement of tumor cell migration. We found that LMNB1 exert critical roles in glioma progression may via regulation of PI3K/Akt signaling pathway. These observations suggest that LMNB1 holds clinical potential for diagnostic and prognostic applications in glioma, presenting novel targets for drug development.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Serotonin Levels and Unchanged Glutamate and GABA Levels in Thalamic Microdialysates Despite Reduced Cell Numbers in a Valproic Acid-Induced Autism Model","authors":"Hakan Ay,&nbsp;Erdal Horata,&nbsp;Elif Mine Öncü Kaya,&nbsp;Orhan Tansel Korkmaz","doi":"10.1007/s11064-024-04299-2","DOIUrl":"10.1007/s11064-024-04299-2","url":null,"abstract":"<div><p>Autism spectrum disorders (ASDs) are increasingly prevalent neurodevelopmental disorders characterized by deficits in social skills, abnormal sensory responses and a loss of neuronal cells. A key factor in these differences is thought to be an imbalance between excitation and inhibition. The aim of this study was to measure the levels of γ-aminobutyric acid (GABA), glutamate (GLU) and serotonin (5-HT) in the thalamus of a rat valproic acid (VPA)-induced ASD model and to correlate these levels with the number of thalamic cells. Ten pregnant Wistar rats were injected with 600 mg/kg VPA on Day 12.5 of gestation, whereas five control rats received saline. After the behavioral tests, the male pups were divided into ASD and control groups with ten animals each. At 55 days of age, pups underwent microdialysis under anesthesia, and thalamic samples were analyzed for GABA, GLU and 5-HT levels by ultrahigh-performance liquid chromatography (UHPLC). After microdialysis, the brain sections were stained, and the volumes of the thalamus and hemispheres were calculated using the Cavalieri method, with the number of neurons and glia determined using the optical fractionator method. Compared with the control group, the ASD group presented increased 5-HT levels, an increased hemispheric volume, a decreased thalamic volume and decreased numbers of thalamic neurons and glia. A negative correlation was observed between the GLU content and glial number in the control group but not in the ASD group. These results indicate a disturbed thalamic neurotransmitter balance. We suggest that the increased thalamic 5-HT levels in ASD rats indicates that 5-HT reuptake is inhibited by the GLU content, which remains unchanged, despite the reduced cell number.</p></div>","PeriodicalId":719,"journal":{"name":"Neurochemical Research","volume":"50 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142778475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}