Annals of Clinical and Experimental Neurology最新文献

{"title":"Changes in contractile characteristics of rat skeletal muscles associated with P2-receptor activation after spinal cord transection","authors":"A. E. Khairullin, D. V. Efimova, M. A. Mukhamedyarov, M. Baltin, T. Baltina, S. Grishin, A. Ziganshin","doi":"10.17816/acen.1012","DOIUrl":"https://doi.org/10.17816/acen.1012","url":null,"abstract":"Introduction. Traumatic spinal cord and peripheral-nerve injury is associated with release of proinflammatory cytokines and chemokines, which may stimulate neuronal activity. Adenosine triphosphoric acid (ATP) is an important pain mediator involved in the acute and chronic neuropathic pain development. Its excessive release from primary injured tissue leads to activation of P2-receptors, which may further start secondary injury mechanisms. Although the effects of ATP on the peripheral nervous system are relatively well studied, the pathophysiological role of purinergic signaling after spinalization remains unclear. \u0000The study was aimed at assessing the post-spinalization effects of P2-receptors on the contractile characteristics of rat skeleton muscles. \u0000Materials and methods. The objects of the study were the soleus muscle, the extensor digitorum longus (EDL) muscle, and diaphragm in intact rats and spinalized rats. Seven days after laminectomy followed by spinal cord transection, animals were anesthetized, exsanguinated, and their muscles with nerve stumps were isolated. Contractile response parameters were recorded using mechanomyography (MMG). To study effects of ATP on ligand binding, ATP was added to a bath and mechanical responses in the rat muscles were assessed 7 min after. After washing with Krebs–Henseleit solution, the preparations were incubated with suramin solution for 20 min with subsequent ATP application. Then the mechanical responses in the muscles were again recorded. Statistical significance was assessed using Student's t-test for independent (unpaired) and paired samples. \u0000Results. We found a significant (p 0.05) decrease in the modulating activity of ATP, as the main endogenous signaling agent, in the cholinergic synapse of the soleus muscle from 32.4 to 5.8% and from 13.7 to 5.6% for the EDL muscle after the spinalization (spinal cord injury at the Th6–Th7 level) compared with intact animals. No such dramatic changes were observed in the diaphragm. \u0000Conclusions. Abnormal ATP-mediated modulation of neuromuscular transmission demonstrated in this study supports the involvement of purinergic signaling in the neurotrophic control and functioning of various motor units.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":" 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141670451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgical Treatment Options for Degenerative Lumbosacral Spinal Stenosis","authors":"Adilya R. Yusupova, A. Gushcha, S. Arestov, D. Petrosyan, R. Kartavykh, A. Simonyan, Andrey A. Kiselev","doi":"10.54101/acen.2024.1.9","DOIUrl":"https://doi.org/10.54101/acen.2024.1.9","url":null,"abstract":"Degenerative spinal stenosis is the most common type of degenerative and dystrophic spine disease. The clinical picture of stenosis, which may include axial pain syndrome, leg pain, intermittent claudication syndrome, weakness and loss of sensitivity in the legs, and impaired pelvic functions, can significantly worsen patients’ quality of life and reduce their ability to work and lead an active lifestyle. \u0000Degenerative spinal stenosis mostly affects the elderly. Therapeutic and neurological communities have stereotypes about spine surgery being too traumatic and invasive, and, therefore, they believe that their use should be contraindicated to and limited in elderly patients. However, surgeons are increasingly giving preference to minimally invasive interventions with high efficacy and safety together with a low risk of complications. \u0000We aimed at reviewing current treatment methods for degenerative lumbosacral spinal stenosis with an emphasis on surgical treatment methods.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":"16 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140740099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in Clinical and Network Functional Connectivity Parameters in Motor Networks and Cerebellum Based on Resting-State Functional Magnetic Resonance Imaging Data in Patients with Post-Stroke Hemiparesis Receiving Interactive Brain Stimulation Neurotherapy","authors":"Nadezhda A. Khrushcheva, K. Kalgin, Andrey A. Savelov, A. V. Shurunova, E. V. Predtechenskaya, M. Shtark","doi":"10.54101/acen.2024.1.4","DOIUrl":"https://doi.org/10.54101/acen.2024.1.4","url":null,"abstract":"Introduction. Interactive brain stimulation (IBS) neurotherapy is an advanced neurofeedback technology (NFB) that involves the organization of a feedback “target” based on signals recorded by functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). The NFB allows patients to volitionally self-regulate their current brain activity and may therefore be a useful treatment option for diseases with altered activation and functional connectivity (FC) patterns. \u0000Our objective was to assess the effects of IBS on the FC changes in motor networks and correlations between clinical and network parameters in patients with post-stroke hand paresis. \u0000Materials and methods. Patients with a history of stroke 2 months were randomized into a main group (n = 7) and a control group (n = 7). All the patients followed the stroke physical rehabilitation for 3 weeks. The main group received IBS training, where the patients learned to imagine movements of the paretic hand trying to amplify the fMRI signal from the primary motor cortex (M1) and the supplementary motor area (SMA) on the lesion side with simultaneous desynchronizing the μ- and β-2 EEG rhythms in the central leads. Clinical tests and MRI were performed prior to and immediately after the treatment. FC matrices were constructed using CONN software based on resting-state fMRI data. \u0000Results. By the end of the training, M1–M1 functional connectivity in the control group weakened, while no changes were observed in the main group. The FC strength was positively correlated with the grip strength (ρ = 0.69; p 0.01) and with the results of the Box and Blocks test (BBT score, ρ = 0.72; p 0.01) and the Fugl-Meyer assessment for upper extremity (FM-UE score, ρ = 0.87; p 0.005). Ipsilesional SMA connectivity with contralesional cerebellum weakened (p 0.05 in the main group). Its strength was negatively correlated with the BBT and FM-UE scores (both tests ρ = –0.44; p 0.05). \u0000Conclusions. Volitional control of M1 and SMA activity in the lesion hemisphere during the post-stroke IBS training alters the architecture of the entire motor network affecting clinically significant FC types. We studied a possible mechanism of this technology and its potential use in treatment programs.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":"24 24","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140738810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of PEGylated Interferons for Relapsing-Remitting Multiple Sclerosis in Adult Patients: Results of Matching-Adjusted Indirect Comparison","authors":"T. Simaniv, M. Zakharova, K. V. Sapozhnikov, D. Tolkacheva, Valeriia D. Sokolova, N. Sableva, O. Mironenko, Taras V. Khimich","doi":"10.54101/acen.2024.1.5","DOIUrl":"https://doi.org/10.54101/acen.2024.1.5","url":null,"abstract":"Introduction. Beta interferons are effective and safe agents for the treatment of relapsing-remitting multiple sclerosis (RRMS). PEGylated interferons have been developed in order to increase patient adherence. Direct comparisons of the efficacy and safety of PEGylated interferons have not yet been conducted. \u0000Our objective was to evaluate the efficacy and safety of SamPEG-IFN-β1a versus PEG-IFN-β1a in adult patients with RRMS. \u0000Materials and methods. We conducted a systematic search of randomized clinical trials (RCTs) using the PubMed, Embase and eLIBRARY.RU databases. Efficacy was assessed based on the proportion of patients with disease relapses and the annualized relapse rate (ARR) during the 1st and the 2nd years of treatment. Safety was assessed by the number of patients with adverse events (AEs), serious AEs (SAEs), and any AEs that led to the treatment discontinuation. We conducted pairwise matching-adjusted indirect comparison (MAIC) to assess comparative efficacy of PEGylated IFNs. To evaluate the efficacy, hypotheses of non-inferiority of SamPEG-IFN-β1a to PEG-IFN-β1a and superiority of SamPEG-IFN-β1a over PEG-IFN-β1a were tested. \u0000Results. Based on results of the systematic review, four articles were selected wherein the results of phase 3 clinical trial of PEG-IFN-β1a and phase 2–3 clinical trial of SamPEG-IFN-β1a were described. In PEG-IFN-β1a group (n = 512) the agent was administered once every 2 weeks, in SamPEGIFN-β1a group (n = 114) the agent was administered at a dose of 240 μg. The analysis results confirmed the hypothesis of SamPEG-IFN-β1a non-inferiority to PEG-IFN-β1a in efficacy, while SamPEG-IFN-β1a superiority over PEG-IFN-β1a in efficacy was not confirmed. The hypothesis of SamPEG-IFN-β1a superiority over PEG-IFN-β1a in safety was also confirmed based on a significantly lower incidence of SAEs and any AEs that led to treatment discontinuation. \u0000Conclusions. The proportion of patients with relapses and the ARR in 1 year and in 2 years of therapy indicates that SamPEG-IFN-β1a is non-inferior to PEG-IFN-β1a in efficacy. SamPEG-IFN-B1a demonstrated a more favourable safety profile than PEG-IFN-B1a as showing less odds of SAEs and AEs leading to treatment discontinuation.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":"13 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140740037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroplasticity, music, and human brain","authors":"I. Bogolepova, M. Krotenkova, R. N. Konovalov, P. A. Agapov, I. G. Malofeeva, A. T. Bikmeev","doi":"10.54101/acen.2024.1.8","DOIUrl":"https://doi.org/10.54101/acen.2024.1.8","url":null,"abstract":"Introduction. Studying the influence of music on the human brain is one of the key topics in neuroscience as it allows extending our understanding of brain neuroplasticity. \u0000This study aimed to investigate structural brain organization in professional musicians. \u0000Materials and methods. We investigated 27 brains (i.e. 54 hemispheres) of male musicians, female musicians, male non-musicians, and female non-musicians by magnetic resonance imaging. All study participants were aged 20 to 30 years and did not have any mental or neurological disorders. Gray matter volume and cortex thickness in different cortical structures of the right and left hemispheres were measured. \u0000Results. We found major changes in the brain structure in professional musicians (both male and female) vs. non-musicians. We found differences in the macroscopic structure of the triangular region in the Broca’s motor speech area in musicians’ brain. Increases in gray matter volume in the brain of musicians and its individual cortical structures were shown in the superior temporal region, Broca’s motor speech area, hippocampus, superior parietal lobule, and other structures. We found increased thickness of cortical structures in musicians vs. non-musicians. \u0000Conclusions. Practicing music regularly was shown to change structural brain organization; we found significant increases in gray matter volume and cortex thickness in various cortical structures in the right and left brain hemispheres of musicians vs. non-musicians.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":"92 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140736200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroimaging Markers for Differential Diagnosis Between Multifocal Motor Neuropathy and Multifocal Acquired Demyelinating Sensory and Motor Neuropathy","authors":"T. Tumilovich, V. V. Sinkova, D. Grishina, N. Suponeva, S. Morozova, M. Krotenkova, Anna V. Mansurova, A. Chechetkin","doi":"10.54101/acen.2024.1.3","DOIUrl":"https://doi.org/10.54101/acen.2024.1.3","url":null,"abstract":"Introduction. Similar asymmetric patterns of motor disorders and neurophysiological changes complicate the differential diagnosis between multifocal motor neuropathy (MMN) and multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) as two chronic dysimmune neuropathies with significantly different treatment approaches. The lack of specific paraclinical markers often result in misdiagnosis and selection of ineffective specific therapy. Identification of specific neuroimaging biomarkers to differentiate these conditions may improve diagnostic approaches. \u0000Objective: To identify neuroimaging markers for the differential diagnosis between MMN and MADSAM. \u0000Materials and methods. The study included 65 participants, particularly 30 individuals with MMN and 35 individuals with MADSAM followed up in the Center of Peripheral Nervous System Diseases, Research Center of Neurology, Moscow, Russia. We retrospectively analyzed their clinical and epidemiological characteristics as well as ultrasonography and magnetic resonance imaging (MRI) findings. \u0000Results. Ultrasonography was performed on the peripheral nerves of the upper extremities, the spinal nerves, and the brachial plexus. The results showed that participants with MADSAM had significantly greater cross-sectional areas (CSAs) and a higher incidence of intraneural ultrasonographic abnormalities compared to participants with MMN. CSA thresholds of the median nerves were identified using ROC analysis to differentiate between MMN and MADSAM. MRI scans of the brachial plexus revealed no abnormalities in 41.4% of the individuals with MMN and 27.3% of the individuals with MADSAM. Meanwhile, STIR hyperintense signal from the brachial plexus was most typical ( 70%) for the MADSAM group. \u0000Conclusions. This was the first detailed comparative analysis of neuroimaging findings in a large sample of patients with either MMN or MADSAM in Russia. Ultrasonographic markers for differential diagnosis have been determined. The advantages and limitations of ultrasonography and MRI of the brachial plexus and the spinal and peripheral nerves in diagnosing multifocal chronic dysimmune neuropathies have been demonstrated.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140737760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-Mediated Immunity in Multiple Sclerosis Patients Who Discontinued Therapy with an Integrin Inhibitor","authors":"Yuliana A. Belova, Y. Chuksina, S. V. Kotov, I. A. Vasilenko","doi":"10.54101/acen.2024.1.2","DOIUrl":"https://doi.org/10.54101/acen.2024.1.2","url":null,"abstract":"Introduction. Natalizumab (NTZ) is a humanized monoclonal antibody (mAb) that selectively inhibits α4-integrin adhesion molecule located on the surface of lymphocytes and prevents their trafficking into the central nervous system (CNS). \u0000The aim of this study was to identify characteristics of lymphocyte population and subpopulation pattern in the peripheral blood (PB) of multiple sclerosis (MS) patients who discontinued NTZ due to an increased risk of developing developing progressive multifocal leukoencephalopathy. \u0000Materials and methods. We conducted an open-label prospective observational study in 26 MS patients. Of those, 6 patients had rapidly progressive MS, 10 patients discontinued NTZ and had confirmed relapses afterwards, and 10 patients received NTZ and had no relapses during the washout period. Ten apparently healthy individuals were used as controls. Cell-mediated immunity parameters were evaluated by flow cytometry using a panel of mAbs to differentiation antigens of PB lymphocytes. \u0000Results. Patients who discontinued NTZ had significantly decreased absolute lymphocyte counts in PB, decreased T-cytotoxic, NKT and B1 lymphocyte subpopulation levels, and decreased activated T-cell (CD3+HLA–DR+) levels, which may be related to their redistribution, passing through the blood-brain barrier, and trafficking into the central nervous system. CD20+ В-cell levels did not differ from normal. Additional immune predictors of MS relapses after NTZ discontinuation can include decreased absolute count of PB lymphocytes and decreased percentage of CD3+CD8+ T-cell, NKT-cell, and B1-cell (CD19+CD5+) subpopulations. Significantly increased levels of CD25+- and CD38+-activated B-cells compared with the normal levels in naïve patients and subjects without relapses after NTZ discontinuation may suggest a high activation potential of the circulating B-cell pool and, therefore, a high risk of MS relapses. \u0000Conclusions. The changes in the lymphocyte subpopulation pattern in the PB of MS patients after NTZ discontinuation may have a prognostic value for assessing the risk of relapses; they justified switching patients to anti-B-cell therapy.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":"41 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140739318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PreventS-MD®: a New Digital Technology to Maintain Cardiovascular Prevention in Routine Clinical Practice","authors":"Mikhail A. Kravchenko, E. Gnedovskaya, Valery L. Feigin, M. Piradov","doi":"10.54101/acen.2024.1.10","DOIUrl":"https://doi.org/10.54101/acen.2024.1.10","url":null,"abstract":"Stroke, myocardial infarction (MI), and other main non-communicable diseases (NCDs) remain major causes of mortality and disability globally. Up to 80% of cardiovascular events and up to 60% of NCDs are associated with potentially controlled risk factors (RFs). State-of-the-art digital technologies can help bridge the gap between evidence-based prevention methods and their critically low availability in routine clinical practice. \u0000An innovative digital platform named PreventS-MD® is a specially developed tool for healthcare professionals to be used under time constraints. With PreventS-MD®, clinicians can estimate patient's 10-year cardiovascular risk within several minutes. Then, they automatically get adapted results and recommendations to address identified RFs as well as graphical representation of specific RF contribution to overall stroke and MI risks. If some additional time is available, the clinician and the patient can collaboratively set customized achievable goals to correct modifiable RFs. An integrated analytical module provides healthcare managers with current digital risk profiles of the relevant population to evaluate prevention effectiveness and to forecast the load throughout the healthcare levels. \u0000PreventS-MD® has several unique advantages, including time-saving design, the function to activate motivated RF correction, individually tailored recommendations, and information on personally changed digital profiles of vascular risks. As cardiovascular diseases and main NCDs have a lot of common RFs, PreventS-MD® implemented into routine clinical practice will utilize a complex approach to the prevention of main NCDs, decreasing both stroke and MI burden and addressing complications of chronic pulmonary and kidney disease, tumors of any type, dementia, etc.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":"59 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140739475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key Risk Factors for Intracerebral Hemorrhage According to Regional Population-Based Stroke Registry","authors":"M. Yu. Maksimova, S. A. Chugunova","doi":"10.54101/acen.2024.1.1","DOIUrl":"https://doi.org/10.54101/acen.2024.1.1","url":null,"abstract":"Introduction. Intracerebral hemorrhage (ICH) registry data allow assessing epidemiological parameters and risk factors in different age, gender, race, ethnicity, and other subgroups. \u0000This study aimed to evaluate the prevalence of key risk factors in a group of Yakutsk residents with primary hypertensive ICH included in the regional population-based stroke registry from 2015 to 2017. \u0000Materials and methods. This study of risk factors was conducted in patients with hypertensive ICH (n = 251) from the regional population-based stroke registry, including 133 (53%) men and 118 (47%) women of Asian or Caucasian races. We performed statistical analysis of data. \u0000Results. The analysis of risk factors showed that the prevalence of smoking and excessive alcohol consumption was higher in men with ICH compared with women (p 0.001). There were no statistically significant differences in the incidence of hypertension, history of myocardial infarction, dyslipidemia, or diabetes mellitus in patients with ICH in gender or ethnicity subgroups. Fibrillation and other heart diseases were more common in Caucasian patients than in Asian (p = 0.005). ICH was associated with high levels of low-density lipoproteins and triglycerides with low levels of total cholesterol and high-density lipoproteins compared with healthy individuals. \u0000Conclusions. We described gender and ethnic differences in the prevalence of risk factors in patients with hypertensive ICH.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":"22 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140740084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3,5-Dimethyladamantan-1-amine Restores Short-term Synaptic Plasticity by Changing Function of Excitatory Amino Acid Transporters in Mouse Model of Spinocerebellar Ataxia Type 1","authors":"O. Belozor, A. A. Vasilev, Alexandra G. Mileiko, Liudmila D. Mosina, Ilya G. Mikhailov, A. Shuvaev, A. Shuvaev","doi":"10.54101/acen.2024.1.7","DOIUrl":"https://doi.org/10.54101/acen.2024.1.7","url":null,"abstract":"Introduction. Memantine is an agent that used for treatment of Alzheimer's type dementia. Memantine considerably reduces the effects of neurodegeneration, may potentially slow down the neurodegenerative changes in the cerebellum and may act as treatment of choice for spinocerebellar ataxia type 1 (SCA 1). \u0000Our objective was to study molecular mechanisms of the short-term synaptic plasticity improvement associated with long-term memantine use in SCA 1 transgenic mice. \u0000Materials and methods. The experiments were performed on 12-week-old CD1 mice. We created a mouse model of cerebellar astrogliosis after expression of mutant ataxin-1 (ATXN1[Q85]) in the Bergmann glia (BG). To model the astrocyte-mediated neurodegeneration in the cerebellum, the mice were injected with LVV GFAP-Flag-ATXN1[Q85] lentiviral vector (LVV) constructs intracortically. Some of the mice received 0.35 mg/kg memantine dissolved in drink water once daily for 9 weeks. The control animals were administered LVV GFAP-ATXN1[Q2]-Flag. Changes of the excitatory postsynaptic currents amplitudes from Purkinje cells (PC) were recorded by patch clamp. Expression of anti-EAAT1 in the cerebellar cortex was assessed using immunohistochemistry. \u0000Results. The reactive glia of the cerebellar cortex in SCA1 mice is characterized by a decrease in the immunoreactivity of anti-EAAT1, while chronic memantine use restores this capacity. The decay time of the excitatory postsynaptic current amplitude in the parallel fiber-Purkinje cell (PF-PC) synapses of the SCA1 mice is considerably longer, which indicates the slowing of glutamate reuptake and EAAT1 dysfunction. The prolonged presence of increased neurotransmitter levels in the synaptic cleft facilitates activation of the mGluR1 signaling and restoration of mGluR1-dependent synaptic plasticity in Purkinje cells of the SCA1 mice. \u0000Conclusions. The slowing of neurotransmitter reuptake associated with long-term memantine treatment improves mGluR1-dependent short-term synaptic plasticity of the Purkinje cells in the SCA1 mice. Restoration of synaptic plasticity in these animals may underlie partial reduction of ataxic syndrome.","PeriodicalId":36946,"journal":{"name":"Annals of Clinical and Experimental Neurology","volume":"5 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140736947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}