Lacosamide exhibits neuroprotective effects in a rat model of Parkinson's disease

IF 2.7 4区医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of chemical neuroanatomy Pub Date : 2023-10-01 DOI:10.1016/j.jchemneu.2023.102311

Burcin Bilal , Mehmet Kirazlar , Mumin Alper Erdogan , Gurkan Yigitturk , Oytun Erbas

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Abstract

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.

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拉科沙胺在帕金森病大鼠模型中显示神经保护作用

背景帕金森病（PD）是一种慢性进行性神经退行性疾病，主要影响运动系统。尽管有几种治疗方法可以缓解帕金森病症状，但目前还没有治愈方法。Lacosamide是一种抗癫痫药物，作为PD的潜在神经保护剂，在临床前研究中显示出了有希望的结果。在本研究中，方法将20只成年雄性大鼠随机分为以下三组（n=7）：1组接受二甲基亚砜立体定位输注（载体，第1组），另一组接受鱼藤酮立体定位输输注（第2组和第3组）。10天后对大鼠进行阿扑吗啡诱导的旋转试验。此后，第2组给予等渗盐水，而第3组给予拉沙酰胺（20mg/kg，腹腔注射）28天。进行阿扑吗啡诱导的旋转试验，以评估拉沙酰胺对运动功能的影响。此外，采用免疫组织化学和生物化学方法分别评估黑质多巴胺能神经元的损失和MDA、TNF-α和HVA水平。结果鱼藤酮诱导的帕金森病大鼠丙二醛和TNF-α水平显著升高，HVA水平降低，而lacosamide治疗的小鼠丙二醛、TNF-α含量显著降低，HVA含量升高。与未治疗组相比，经拉沙酰胺治疗的小鼠的阿扑吗啡诱导的旋转测试得分较低。此外，拉沙酰胺治疗显著减轻了源自黑质的纹状体内多巴胺能投射的变性，并增加了酪氨酸羟化酶（TH）免疫荧光，这表明多巴胺能神经元功能得以保留。结论我们的研究为拉沙酰胺对帕金森病大鼠模型具有神经保护作用提供了证据。需要进一步研究其潜在机制，并评估拉沙酰胺作为帕金森病神经保护剂的潜在临床应用。

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来源期刊

Journal of chemical neuroanatomy 医学-神经科学

CiteScore

4.50

自引率

3.60%

发文量

审稿时长

62 days

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.