{"title":"拉科沙胺在帕金森病大鼠模型中显示神经保护作用","authors":"Burcin Bilal , Mehmet Kirazlar , Mumin Alper Erdogan , Gurkan Yigitturk , Oytun Erbas","doi":"10.1016/j.jchemneu.2023.102311","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Parkinson's disease<span><span><span> (PD) is a chronic and progressive neurodegenerative disorder that primarily affects the motor system. Although there are several treatments available to alleviate PD symptoms, there is currently no cure for the disease. </span>Lacosamide<span>, an anti-epileptic drug, has shown promising results in preclinical studies as a potential </span></span>neuroprotective agent for PD. In this study, we aimed to investigate the neuroprotective effect of lacosamide in a murine model of PD.</span></p></div><div><h3>Methods</h3><p>Twenty-one adult male rats were randomly divided into the following three groups (<em>n</em><span><span><span> = 7): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1), and the others received stereotaxical infusion of </span>rotenone (groups 2 and 3). The apomorphine-induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered lacosamide (20 mg/kg,i.p.) for 28 days. Apomorphine-induced rotation tests were performed to assess the effect of lacosamide on motor function. In addition, </span>immunohistochemistry<span><span><span> and biochemistry<span> were used to assess the dopaminergic neuron loss in the </span></span>substantia nigra and MDA, TNF-α and </span>HVA levels, respectively.</span></span></p></div><div><h3>Results</h3><p>In rats with Parkinson's disease induced by rotenone, levels of malondialdehyde and TNF-α significantly increased and HVA levels decreased, whereas in mice treated with lacosamide, levels of malondialdehyde and TNF-α significantly decreased and HVA levels increased. The apomorphine-induced rotation test scores of lacosamide-treated mice were lower compared with the untreated group. Furthermore, treatment with lacosamide significantly mitigated the degeneration of dopaminergic projections within the striatum originating from the substantia nigra and increased tyrosine hydroxylase (TH) immunofluorescence, indicative of preserved dopaminergic neuronal function.</p></div><div><h3>Conclusion</h3><p>In conclusion, our study provides evidence that lacosamide has a neuroprotective effect on the rat model of PD. Further studies are required to investigate the underlying mechanisms and evaluate the potential clinical use of lacosamide as a neuroprotective agent for PD.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"132 ","pages":"Article 102311"},"PeriodicalIF":2.7000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lacosamide exhibits neuroprotective effects in a rat model of Parkinson's disease\",\"authors\":\"Burcin Bilal , Mehmet Kirazlar , Mumin Alper Erdogan , Gurkan Yigitturk , Oytun Erbas\",\"doi\":\"10.1016/j.jchemneu.2023.102311\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Parkinson's disease<span><span><span> (PD) is a chronic and progressive neurodegenerative disorder that primarily affects the motor system. Although there are several treatments available to alleviate PD symptoms, there is currently no cure for the disease. </span>Lacosamide<span>, an anti-epileptic drug, has shown promising results in preclinical studies as a potential </span></span>neuroprotective agent for PD. In this study, we aimed to investigate the neuroprotective effect of lacosamide in a murine model of PD.</span></p></div><div><h3>Methods</h3><p>Twenty-one adult male rats were randomly divided into the following three groups (<em>n</em><span><span><span> = 7): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1), and the others received stereotaxical infusion of </span>rotenone (groups 2 and 3). The apomorphine-induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered lacosamide (20 mg/kg,i.p.) for 28 days. Apomorphine-induced rotation tests were performed to assess the effect of lacosamide on motor function. In addition, </span>immunohistochemistry<span><span><span> and biochemistry<span> were used to assess the dopaminergic neuron loss in the </span></span>substantia nigra and MDA, TNF-α and </span>HVA levels, respectively.</span></span></p></div><div><h3>Results</h3><p>In rats with Parkinson's disease induced by rotenone, levels of malondialdehyde and TNF-α significantly increased and HVA levels decreased, whereas in mice treated with lacosamide, levels of malondialdehyde and TNF-α significantly decreased and HVA levels increased. The apomorphine-induced rotation test scores of lacosamide-treated mice were lower compared with the untreated group. Furthermore, treatment with lacosamide significantly mitigated the degeneration of dopaminergic projections within the striatum originating from the substantia nigra and increased tyrosine hydroxylase (TH) immunofluorescence, indicative of preserved dopaminergic neuronal function.</p></div><div><h3>Conclusion</h3><p>In conclusion, our study provides evidence that lacosamide has a neuroprotective effect on the rat model of PD. Further studies are required to investigate the underlying mechanisms and evaluate the potential clinical use of lacosamide as a neuroprotective agent for PD.</p></div>\",\"PeriodicalId\":15324,\"journal\":{\"name\":\"Journal of chemical neuroanatomy\",\"volume\":\"132 \",\"pages\":\"Article 102311\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2023-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of chemical neuroanatomy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0891061823000819\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of chemical neuroanatomy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0891061823000819","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Lacosamide exhibits neuroprotective effects in a rat model of Parkinson's disease
Background
Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder that primarily affects the motor system. Although there are several treatments available to alleviate PD symptoms, there is currently no cure for the disease. Lacosamide, an anti-epileptic drug, has shown promising results in preclinical studies as a potential neuroprotective agent for PD. In this study, we aimed to investigate the neuroprotective effect of lacosamide in a murine model of PD.
Methods
Twenty-one adult male rats were randomly divided into the following three groups (n = 7): 1 group received stereotaxical infusion of dimethyl sulfoxide (vehicle, group 1), and the others received stereotaxical infusion of rotenone (groups 2 and 3). The apomorphine-induced rotation test was applied to the rats after 10 days. Thereafter, group 2 was administered isotonic saline, whereas group 3 was administered lacosamide (20 mg/kg,i.p.) for 28 days. Apomorphine-induced rotation tests were performed to assess the effect of lacosamide on motor function. In addition, immunohistochemistry and biochemistry were used to assess the dopaminergic neuron loss in the substantia nigra and MDA, TNF-α and HVA levels, respectively.
Results
In rats with Parkinson's disease induced by rotenone, levels of malondialdehyde and TNF-α significantly increased and HVA levels decreased, whereas in mice treated with lacosamide, levels of malondialdehyde and TNF-α significantly decreased and HVA levels increased. The apomorphine-induced rotation test scores of lacosamide-treated mice were lower compared with the untreated group. Furthermore, treatment with lacosamide significantly mitigated the degeneration of dopaminergic projections within the striatum originating from the substantia nigra and increased tyrosine hydroxylase (TH) immunofluorescence, indicative of preserved dopaminergic neuronal function.
Conclusion
In conclusion, our study provides evidence that lacosamide has a neuroprotective effect on the rat model of PD. Further studies are required to investigate the underlying mechanisms and evaluate the potential clinical use of lacosamide as a neuroprotective agent for PD.
期刊介绍：
The Journal of Chemical Neuroanatomy publishes scientific reports relating the functional and biochemical aspects of the nervous system with its microanatomical organization. The scope of the journal concentrates on reports which combine microanatomical, biochemical, pharmacological and behavioural approaches.
Papers should offer original data correlating the morphology of the nervous system (the brain and spinal cord in particular) with its biochemistry. The Journal of Chemical Neuroanatomy is particularly interested in publishing important studies performed with up-to-date methodology utilizing sensitive chemical microassays, hybridoma technology, immunocytochemistry, in situ hybridization and receptor radioautography, to name a few examples.
The Journal of Chemical Neuroanatomy is the natural vehicle for integrated studies utilizing these approaches. The articles will be selected by the editorial board and invited reviewers on the basis of their excellence and potential contribution to this field of neurosciences. Both in vivo and in vitro integrated studies in chemical neuroanatomy are appropriate subjects of interest to the journal. These studies should relate only to vertebrate species with particular emphasis on the mammalian and primate nervous systems.
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