Acta neurobiologiae experimentalis最新文献

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Effects of chronic cuff electrode implantation and stimulation of the rat tibial nerve: ultrastructural analysis of myelinated axons and their microenvironment. 慢性袖带电极植入和刺激大鼠胫神经的影响:髓鞘轴突及其微环境的超微结构分析。
IF 1.4 4区 医学
Acta neurobiologiae experimentalis Pub Date : 2025-04-17 DOI: 10.55782/ane-2024-2660
Olga Gajewska-Woźniak, Julita Czarkowska-Bauch, Andrzej Szczepankiewicz, Małgorzata Skup
{"title":"Effects of chronic cuff electrode implantation and stimulation of the rat tibial nerve: ultrastructural analysis of myelinated axons and their microenvironment.","authors":"Olga Gajewska-Woźniak, Julita Czarkowska-Bauch, Andrzej Szczepankiewicz, Małgorzata Skup","doi":"10.55782/ane-2024-2660","DOIUrl":"https://doi.org/10.55782/ane-2024-2660","url":null,"abstract":"<p><p>Numerous experimental data point to therapeutic effects of electrical stimulation of peripheral nerves. Stimulation of low‑threshold proprioceptive afferents to motoneurons (MNs) innervating the ankle extensor muscles of the rat increases glutamatergic Ia MN inputs and spinal and muscle expression of neurotrophin‑3, instrumental for proprioceptive afferent‑MN connections. We aimed to examine morphological consequences of the cuff electrode implanted around the tibial nerve used for chronic stimulation which may cause unwanted effects through its long‑lasting contact with the nerve. We addressed also the questions if stimulation of low‑threshold proprioceptive afferents may contribute to neural damage, affect capillary vessels and macrophage morphology reflecting functional state of the nerve. Their consequences on axonal and nerve ultrastructure have not been previously evaluated. To examine the effect of cuff electrodes and of 7‑day low‑threshold stimulation applied in the 4th week post‑implantation on the tibial nerve, electrodes were implanted bilaterally, and a stimulation was added unilaterally. Non‑implanted group was the control. The counts of myelinated axons, their cross‑sectional area (>1 μm2) and circularity were measured on photomicrographs captured with use of light microscope from semi‑thin Epon sections stained with toluidine blue. Ultrastructural observations with TEM included myelin, axoplasm, Remak fibers, blood vessels, macrophages and fibroblasts. Four weeks after implantation of the cuff, the mean cross‑sectional area of the nerve, and counts, area and diameter of the myelinated fibers were lower compared to control. The largest fibers located in the external parts of the main nerve branches and dispersed in small branches were changed the most. No significant difference in either parameter between unstimulated (NS) and stimulated (S) nerve was found. Axons in Remak bundles were dispersed comparably in NS and S nerves. Thinly myelinated fibers demonstrating features of demyelination with remyelination were identified. We provide evidence that long-lasting presence of the cuff electrode is not neutral for nerve structure, causing mild shrinkage of large myelinated axons and impairment of organization of unmyelinated fibers. Since we demonstrated that low‑threshold proprioceptive stimulation of the tibial nerve results in a stable Hoffmann reflex and induces synaptic plasticity by increasing glutamatergic input to MNs, we conclude that the applied protocol maintains an adequate margin of safety.</p>","PeriodicalId":7032,"journal":{"name":"Acta neurobiologiae experimentalis","volume":"85 1","pages":"1-15"},"PeriodicalIF":1.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Status epilepticus‑induced neuronal degeneration in the immature rat zona incerta is confined to its rostral sector. 癫痫持续状态诱导的未成熟大鼠间带神经元变性局限于其吻侧区。
IF 1.4 4区 医学
Acta neurobiologiae experimentalis Pub Date : 2025-04-17 DOI: 10.55782/ane-2024-2447
Azzat Al-Redouan, Rastislav Druga, Martin Salaj, Hana Kubova
{"title":"Status epilepticus‑induced neuronal degeneration in the immature rat zona incerta is confined to its rostral sector.","authors":"Azzat Al-Redouan, Rastislav Druga, Martin Salaj, Hana Kubova","doi":"10.55782/ane-2024-2447","DOIUrl":"https://doi.org/10.55782/ane-2024-2447","url":null,"abstract":"<p><p>The distribution and morphology of neuronal degeneration were observed and analyzed in each sector of the zona incerta in a lithium‑pilocarpine (LiCl) Wistar rat model of status epilepticus in 12, 15, 18, 21, and 25‑day‑old rats and survival intervals of 4, 8, 12, 24, and 48 hours. Status epilepticus was induced via intraperitoneal (IP) injection of LiCl (3 mmol/kg) 24 hours before an injection of pilocarpine (40 mg/kg, IP). Motor seizures were suppressed by paraldehyde (0.3‑0.6 ml/kg, IP) two hours after status epilepticus onset. Animals were anesthetized using urethane and perfused with phosphate‑buffered saline followed by 4% paraformaldehyde. Brains were sectioned and Nissl stained for map guidance, with fluoro‑Jade B fluorescence used to detect degenerated neurons. Fluoro‑jade B‑positive neurons were plotted to a standard stereotaxic atlas, their distribution was quantified, and their long‑axis diameter was measured. Fluoro‑jade B‑positive neurons were found in pups aged 15 days and older 24 hours after status epilepticus, in which their numbers increased, and their perikaryon size decreased with advancing age. Thus, neuronal damage severity was dependent on age and survival interval. Neuronal damage was only found in the rostral sector of the zona incerta, a region that exhibits a small number of inhibitory neurons and is reciprocally connected to the limbic cortex. This system of hyperactivity, coupled with inhibitory neurons, may be the underlying cause of the neuronal degeneration and explain why it was confined to the rostral sector of the zona incerta.</p>","PeriodicalId":7032,"journal":{"name":"Acta neurobiologiae experimentalis","volume":"85 1","pages":"38-48"},"PeriodicalIF":1.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effects of co‑exposure to caffeine and heavy metals on learning and oxidative stress in mice. 咖啡因和重金属对小鼠学习和氧化应激的影响。
IF 1.4 4区 医学
Acta neurobiologiae experimentalis Pub Date : 2025-04-17 DOI: 10.55782/ane-2024-2647
Katarzyna Zygan-Filipiak, Piotr Adamczuk, Krzysztof Łukawski
{"title":"The effects of co‑exposure to caffeine and heavy metals on learning and oxidative stress in mice.","authors":"Katarzyna Zygan-Filipiak, Piotr Adamczuk, Krzysztof Łukawski","doi":"10.55782/ane-2024-2647","DOIUrl":"https://doi.org/10.55782/ane-2024-2647","url":null,"abstract":"<p><p>Caffeine, a widely consumed psychoactive substance, may affect the neurotoxicity of environmental toxins. The study aimed to investigate the effects of the combined administration of caffeine and heavy metal compounds (cadmium chloride and lead acetate) on brain tissue function, focusing on memory processes and oxidative stress parameters. Adult male Swiss mice were administered substances intraperitoneally for 10 days. A passive avoidance test evaluated long‑term memory, while the Y‑maze assessed spatial working memory. In addition, lipid peroxidation and glutathione levels, as well as superoxide dismutase, catalase, and acetylcholinesterase activity, were determined in mouse brains. The results showed that exposure to caffeine and cadmium or lead caused different neurotoxic effects. Unlike lead, cadmium interacted with caffeine in memory tests. Caffeine protected mice against cadmium‑induced spatial working memory impairment. The combination of caffeine and cadmium impaired learning in the passive avoidance test. Cadmium and lead caused oxidative stress in the brain, and caffeine had a preventive effect against it. The study showed that co‑exposure to caffeine and cadmium could affect learning and memory. The antioxidant activity of caffeine may play a protective role in cadmium‑induced spatial memory impairment.</p>","PeriodicalId":7032,"journal":{"name":"Acta neurobiologiae experimentalis","volume":"85 1","pages":"49-57"},"PeriodicalIF":1.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hydroxycinnamates alleviate chronic unpredictable mild stress‑induced depressive‑like behavior and neuroinflammation in mice. 羟基肉桂酸缓解小鼠慢性不可预测的轻度应激诱导的抑郁样行为和神经炎症。
IF 1.4 4区 医学
Acta neurobiologiae experimentalis Pub Date : 2025-04-17 DOI: 10.55782/ane-2024-2681
Manas Kinra, Niraja Ranadive, Madhavan Nampoothiri, Jayesh Mudgal, Devinder Arora
{"title":"Hydroxycinnamates alleviate chronic unpredictable mild stress‑induced depressive‑like behavior and neuroinflammation in mice.","authors":"Manas Kinra, Niraja Ranadive, Madhavan Nampoothiri, Jayesh Mudgal, Devinder Arora","doi":"10.55782/ane-2024-2681","DOIUrl":"https://doi.org/10.55782/ane-2024-2681","url":null,"abstract":"<p><p>The polyphenolic compounds ferulic acid (FA) and p‑coumaric acid (PCA) have been extensively studied for their free radical scavenging and anti‑inflammatory properties. Both compounds are present in food and beverages commonly consumed globally. Our molecular modeling, in‑vitro, and in‑vivo studies suggest that the compounds may be neuroprotective by modulating the nucleotide‑binding domain, leucine‑rich‑containing family, pyrin domain‑containing‑3 (NLRP3) inflammasome pathway. The current study explored the dose‑dependent neuroprotective potential of FA and PCA in a chronic unpredictable mild stress (CUMS) mouse model. Male Swiss albino mice were divided into nine groups consisting of control (CON), CUMS, FA10 (10 mg/kg FA), FA40 (40 mg/kg FA), FA160 (160 mg/kg FA), PCA10 (10 mg/kg PCA), PCA40 (40 mg/kg PCA), PCA160 (160 mg/kg PCA), and FLX (10 mg/kg fluoxetine). All animals, except the CON group, received random mild stressors for 21 days, and from day 22‑42, the treatments were administered alongside the stressors. Behavioral assessments were performed on day 42, followed by sample collection. Brain homogenates from CUMS‑exposed animals expressed elevated levels of the pro‑inflammatory cytokines interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑alpha (TNF‑α), and oxidative stress markers. Treatment with FA and PCA effectively reduced cytokine release and oxidative stress, alleviating the depressive‑like behavior.</p>","PeriodicalId":7032,"journal":{"name":"Acta neurobiologiae experimentalis","volume":"85 1","pages":"58-66"},"PeriodicalIF":1.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regional cerebral blood flow correlated with aphasia in dementia of the Alzheimer's type and frontotemporal lobar degeneration. 区域脑血流量与阿尔茨海默氏型痴呆和额颞叶变性失语症相关。
IF 1.4 4区 医学
Acta neurobiologiae experimentalis Pub Date : 2025-04-17 DOI: 10.55782/ane-2024-2621
Miho Ota, Yuko Koshibe, Ayako Kitabatake, Masashi Tamura, Takumi Takahashi, Kiyotaka Nemoto, Tetsuaki Arai
{"title":"Regional cerebral blood flow correlated with aphasia in dementia of the Alzheimer's type and frontotemporal lobar degeneration.","authors":"Miho Ota, Yuko Koshibe, Ayako Kitabatake, Masashi Tamura, Takumi Takahashi, Kiyotaka Nemoto, Tetsuaki Arai","doi":"10.55782/ane-2024-2621","DOIUrl":"https://doi.org/10.55782/ane-2024-2621","url":null,"abstract":"<p><p>Individuals with neurocognitive disorders such as dementia of the Alzheimer's type (DAT) and frontotemporal lobar degeneration sometimes show characteristic language dysfunctions. As neurocognitive disorders progress, different types of aphasia may present. To evaluate the disease‑related changes of language functions, and to determine the correlation between the regional cerebral blood flow (rCBF) and language dyfunctions in patients with DAT or the behavioral variant of frontotemporal dementia (bvFTD) or semantic dementia (SD), we used a scale for speech and reading impairment in Japanese (the Standard Language Test for Aphasia [SLTA]), and perfusion single photon emission computed tomography, and we analyzed the relationships among them. Significant differences were identified among the DAT, SD, and bvFTD groups in the SLTA subscales concerning kanji (morphographic) words. There were positive correlations between the SLTA subscales concerning kanji words and the rCBF in left temporo‑occipital regions. The patients with bvFTD showed relative rCBF preservation in the posterior cerebrum compared with the DAT and SD patients. Our results indicate that aphasia for Japanese kanji words might be related to the dysfunction of temporo‑occipital regions, and they suggest that in patients with bvFTD, preserving the CBF in the posterior cerebrum might help maintain the ability to handle morphographic words such as kanji.</p>","PeriodicalId":7032,"journal":{"name":"Acta neurobiologiae experimentalis","volume":"85 1","pages":"29-37"},"PeriodicalIF":1.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dysregulation of miR‑24‑3p and miR‑186‑5p and GABAA receptor expression in focal cortical dysplasia. 局灶性皮质发育不良中miR‑24‑3p、miR‑186‑5p和GABAA受体表达的失调。
IF 1.4 4区 医学
Acta neurobiologiae experimentalis Pub Date : 2025-04-17 DOI: 10.55782/ane-2024-2656
Arpna Srivastava, Yogesh Agarwal, Soumil Dey, Ramesh Doddamani, Mehar Chand Sharma, Manjari Tripathi, Poodipedi Sarat Chandra, Sanjeev Lalwani, Aparna Banerjee Dixit, Jyotirmoy Banerjee
{"title":"Dysregulation of miR‑24‑3p and miR‑186‑5p and GABA<sub>A</sub> receptor expression in focal cortical dysplasia.","authors":"Arpna Srivastava, Yogesh Agarwal, Soumil Dey, Ramesh Doddamani, Mehar Chand Sharma, Manjari Tripathi, Poodipedi Sarat Chandra, Sanjeev Lalwani, Aparna Banerjee Dixit, Jyotirmoy Banerjee","doi":"10.55782/ane-2024-2656","DOIUrl":"https://doi.org/10.55782/ane-2024-2656","url":null,"abstract":"<p><p>Spontaneous synaptic activity mediated by GABAA receptor is associated with epileptogenicity in focal cortical dysplasia (FCD). miRNAs are potentially involved in the regulation of GABAA receptor subunit expression and activity. This study aimed to determine the expression of miRNAs in FCD and correlate their expression level with mRNA levels of GABAA receptor subunits. Expression of GABAA receptor subunits (α1 and α4) and miRNAs (miR‑155‑5p, miR‑186‑5p, and miR‑24‑3p) were evaluated using real‑time PCR in resected brain samples from FCD patients. miRNA levels were also determined in the serum of FCD patients. Spontaneous GABAA receptor‑mediated synaptic activity was measured using patch clamp technique. Significant increase in α1 and α4 subunit expression and miR‑155‑5p levels, while decrease in miR‑24‑3p and miR‑186‑5p levels, was observed in the brain samples of FCD. In the serum of FCD patients, miR‑155‑5p levels were increased, whereas miR‑24‑3p and miR‑186‑5p levels remained unaltered. Increased α4 subunit expression in FCD might be due to reduced levels of miR‑24‑3p and miR‑186‑5p. In addition, reduced miR‑186‑5p levels might be responsible for increased expression of α1 subunit. We also observed an increase in the spontaneous GABAA receptor‑mediated synaptic transmission in FCD. In conclusion, dysregulation of miRNAs and GABAA receptor expression suggest that these miRNAs may contribute to altered GABAA receptor‑mediated synaptic activity in FCD.</p>","PeriodicalId":7032,"journal":{"name":"Acta neurobiologiae experimentalis","volume":"85 1","pages":"16-28"},"PeriodicalIF":1.4,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The phenomenon of sensory processing: historical overview, theoretical models, and neurophysiological underpinnings. 感觉加工现象:历史概述、理论模型和神经生理学基础。
IF 1.4 4区 医学
Acta neurobiologiae experimentalis Pub Date : 2025-01-14 DOI: 10.55782/ane-2024-2556
Natalia Grobelna, Radosław Rutkowski, Filip Rybakowski, Janusz Rybakowski, Ewa Ferensztajn-Rochowiak
{"title":"The phenomenon of sensory processing: historical overview, theoretical models, and neurophysiological underpinnings.","authors":"Natalia Grobelna, Radosław Rutkowski, Filip Rybakowski, Janusz Rybakowski, Ewa Ferensztajn-Rochowiak","doi":"10.55782/ane-2024-2556","DOIUrl":"10.55782/ane-2024-2556","url":null,"abstract":"<p><p>The article provides a review of the sensory processing (SP) phenomenon, its origins, theoretical models, and neurophysiological foundations. Initiated by A. Jean Ayres' research on sensory integration in the 1960s and 70s, this field has evolved, leading to the development of concepts such as Winnie Dunn's four quadrant model and Miller's ecological model of sensory modulation. Over the years, based on theoretical considerations, the concepts of sensory processing disorder and sensory processing sensitivity were formulated. The article highlights the role of temperament and its impact on sensory processing, suggesting that individual differences can significantly affect how people respond to sensory stimuli. The neurophysiological basis including sensory gating, electrodermal responses, and neuroimaging methods is presented. There has been an interest in the relationship between SP and mental disorders in adults, despite the lack of a formal diagnosis in DSM‑5 and ICD classifications. The literature analysis reveals the complexity of the subject, indicating the need for further research in this field.</p>","PeriodicalId":7032,"journal":{"name":"Acta neurobiologiae experimentalis","volume":"84 4","pages":"359-370"},"PeriodicalIF":1.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Piperine relieves neuropathic pain induced by paclitaxel in mice. 胡椒碱可减轻紫杉醇所致小鼠神经性疼痛。
IF 1.4 4区 医学
Acta neurobiologiae experimentalis Pub Date : 2025-01-14 DOI: 10.55782/ane-2024-2590
Toktam Sahranavard, Vahideh Ghorani, Fatemeh Forouzanfar, Samaneh Sadat Asadi Kakhki, Ebrahim Nikfar Dastaki, Ebrahim Golmakani, Ramin Rezaee
{"title":"Piperine relieves neuropathic pain induced by paclitaxel in mice.","authors":"Toktam Sahranavard, Vahideh Ghorani, Fatemeh Forouzanfar, Samaneh Sadat Asadi Kakhki, Ebrahim Nikfar Dastaki, Ebrahim Golmakani, Ramin Rezaee","doi":"10.55782/ane-2024-2590","DOIUrl":"10.55782/ane-2024-2590","url":null,"abstract":"<p><p>Piperine is an amide alkaloid isolated from the black pepper plant. This study examined the pain‑relieving activity of piperine against paclitaxel (PTX)‑induced neuropathy. Male mice were divided into 6 groups: Sham‑operated group (remained intact), PTX group (PTX‑treated mice receiving normal saline), PTX+ piperine 10, 25, and 50 mg/kg groups (PTX‑treated mice receiving piperine) and positive control group (PTX‑treated mice receiving imipramine 10 mg/kg). Neuropathic pain was induced by PTX 2 mg/kg/day on days 1, 3, 5 and 7. On day 7, behavioral tests were conducted and serum levels of interleukin‑6 (IL‑6), tumor necrosis factor‑alpha (TNF‑α), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were assayed. PTX produced significant thermal hyperalgesia compared to the sham group. Piperine at all doses alleviated neuropathic pain, and significantly decreased IL‑6, TNF‑α, and MDA, but induced CAT and SOD activities compared to the control group. Piperine could confer beneficial effects against neuropathic pain, at least partially, via reduction of inflammatory and oxidative stress markers.</p>","PeriodicalId":7032,"journal":{"name":"Acta neurobiologiae experimentalis","volume":"84 4","pages":"332-340"},"PeriodicalIF":1.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Leflunomide exerts neuroprotective effects in an MPTP‑treated mouse model of Parkinsonism. 来氟米特在MPTP治疗的帕金森小鼠模型中发挥神经保护作用。
IF 1.4 4区 医学
Acta neurobiologiae experimentalis Pub Date : 2025-01-14 DOI: 10.55782/ane-2024-2579
Yeşim Civil Ürkmez, Seda Kirmizikan, Caner Günaydin, Esra Cikler, Sirri Bilge, Bahattin Avci, Sebati Sinan Ürkmez
{"title":"Leflunomide exerts neuroprotective effects in an MPTP‑treated mouse model of Parkinsonism.","authors":"Yeşim Civil Ürkmez, Seda Kirmizikan, Caner Günaydin, Esra Cikler, Sirri Bilge, Bahattin Avci, Sebati Sinan Ürkmez","doi":"10.55782/ane-2024-2579","DOIUrl":"10.55782/ane-2024-2579","url":null,"abstract":"<p><p>Neuroinflammation and the immune response are recognized as significant mechanisms contributing to the progression and pathophysiology of Parkinson's disease (PD). Consequently, extensive research is being conducted on drugs targeting inflammation and immune response. Leflunomide, known for its anti‑inflammatory and immunomodulatory properties, is currently used as a disease‑modifying agent for the treatment of rheumatoid arthritis. The objective of this study was to investigate the effect of leflunomide on PD. The PD model was established by administering 18 mg/kg of 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine (MPTP) intraperitoneally for 5 consecutive days. Leflunomide was administered intraperitoneally at doses of 1, 5, and 10 mg/kg for 14 days. Motor and behavioral deficits were assessed using the rotarod test, locomotor activity assessment, hanging wire test, and pole test. MPTP administration impaired motor function and locomotor activity, and caused muscle weakness and bradykinesia. Leflunomide at a dose of 10 mg/kg mitigated the severity of motor deficits and muscle weakness. Furthermore, leflunomide at a dose of 10 mg/kg suppressed the MPTP‑induced elevation of interleukin‑2, interleukin‑6, and tumor necrosis factor‑alpha levels in the brain tissue. Similarly, leflunomide attenuated the increased expression of nuclear factor kappa B and inducible nitric oxide synthase caused by MPTP treatment. Moreover, leflunomide at a dose of 10 mg/kg preserved neuronal integrity and prevented the loss of tyrosine hydroxylase expression induced by MPTP administration. Based on our findings, leflunomide exhibited a beneficial effect on the MPTP‑induced PD model, potentially through modulation of anti‑inflammatory mechanisms.</p>","PeriodicalId":7032,"journal":{"name":"Acta neurobiologiae experimentalis","volume":"84 4","pages":"319-331"},"PeriodicalIF":1.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The integral role of PTEN in brain function: from neurogenesis to synaptic plasticity and social behavior. PTEN在脑功能中的整体作用:从神经发生到突触可塑性和社会行为。
IF 1.4 4区 医学
Acta neurobiologiae experimentalis Pub Date : 2025-01-14 DOI: 10.55782/ane-2024-2657
Natalia Chwin, Anna Kiryk
{"title":"The integral role of <i>PTEN</i> in brain function: from neurogenesis to synaptic plasticity and social behavior.","authors":"Natalia Chwin, Anna Kiryk","doi":"10.55782/ane-2024-2657","DOIUrl":"10.55782/ane-2024-2657","url":null,"abstract":"<p><p>The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene is a critical tumor suppressor that plays an essential role in the development and functionality of the central nervous system. Located on chromosome 10 in humans and chromosome 19 in mice, PTEN encodes a protein that regulates cellular processes such as division, proliferation, growth, and survival by antagonizing the PI3K‑Akt‑mTOR signaling pathway. In neurons, PTEN dephosphorylates phosphatidylinositol‑3,4,5‑trisphosphate (PIP3) to PIP2, thereby modulating key signaling cascades involved in neurogenesis, neuronal migration, and synaptic plasticity. PTEN is crucial for embryonic neurogenesis, controlling the proliferation of neural progenitor cells and guiding the migration and proper lamination of neurons in cortical and hippocampal structures. It also regulates dendritic growth and axon guidance, ensuring correct neuronal connectivity. In postnatal neurogenesis, PTEN maintains the balance of stem cell proliferation and integration of new neurons into existing circuits, particularly in the hippocampal dentate gyrus. Animal models with PTEN deletion or mutation exhibit significant structural and functional neuronal abnormalities, including enlarged soma and dendritic hypertrophy, increased synaptic density, and altered synaptic plasticity mechanisms such as long‑term potentiation and long‑term depression. These changes lead to deficits in learning and memory tasks, as well as impairments in social behaviors. PTEN mutations are associated with neurodevelopmental disorders like intellectual disability, epilepsy, and autism spectrum disorders accompanied by macrocephaly. Understanding PTEN's mechanisms offers valuable insights into its contributions to neurodevelopmental disorders and presents potential therapeutic targets for cognitive impairments and neurodegenerative diseases. Future research should focus on elucidating PTEN's functions in mature neurons and its influence on established neuronal networks, which may have significant implications for memory enhancement and behavioral modifications.</p>","PeriodicalId":7032,"journal":{"name":"Acta neurobiologiae experimentalis","volume":"84 4","pages":"309-318"},"PeriodicalIF":1.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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