帕金森病伴抑郁患者DBS 术后帕罗西汀治疗疗效观察

目的:研究丘脑底核(STN)脑深部电刺激(DBS)治疗帕金森病(PD)合并抑郁障碍术后服用帕罗西汀治疗的疗效。方法:将38例合并抑郁障碍的PD患者随机分为三组,行丘脑底核脑深部电极植入术,术后空白对照组不服用任何抗抑郁药物,药物治疗组服用帕罗西汀每日一次,每次20mg,安慰剂组服用安慰剂。术前一周,术后1个月、2个月和3个月进行随访和临床评价。结果:抑郁患者术后抑郁障碍症状如焦虑、绝望和激越症状也有不同程度好转,应用安慰剂后,患者术后抑郁障碍程度好转程度大于空白对照组(P<0.05),而应用帕罗西汀后术后3个月汉密尔顿抑郁量表评分(HAMD)下降程度显著低于空白对照组及安慰剂组(P<0.05)。结论:表明STN-DBS术后PD患者的抑郁症状有所改善,辅助抗抑郁药物治疗效果更佳。     

新型深部脑刺激模式的开发及研究进展

深部脑刺激(deep brain stimulation,DBS)已成为治疗帕金森病等运动障碍疾病的常规方法之一,并且在许多其他神经和精神疾病的治疗中也具有良好的应用前景.但是,目前常规DBS采用单通道恒定脉冲间隔的高频刺激(high frequency stimulation,HFS),刺激模式缺少多样化,限制了DBS在临床上的推广应用.为了开发更多DBS刺激模式,用于改善疗效、拓展应用范围、并节省刺激器的电能,近年来研究人员基于去同步调控机制,在脉冲序列的时间模式和空间排布两方面开发了DBS新模式.主要包括:变频序列(包括规则变频和随机变频)、不同空间位点上的多通道异步刺激以及变频和多通道两者的结合.这些新刺激模式能够提高DBS的临床疗效、降低刺激能耗,在帕金森病以及癫痫、强迫症和微意识障碍等其他脑疾病的治疗中都展现了良好的应用前景.更值得关注的是,多通道异步刺激不仅在刺激期间具有更好的即时疗效,而且刺激结束后还能长时间保持疗效,具有刺激后效应.这个特性突破了常规DBS主要为即时效应的局限性,展现了DBS新前景.本文在概述常规DBS模式及其去同步调控机制的基础上,综述变频脉冲刺激和...     

Deep brain stimulation: Challenges at the tissue-electrode interface and current solutions

Deep brain stimulation (DBS) is used to treat the motor symptoms of Parkinson's disease patients by stimulating the subthalamic nucleus. However, optimization of DBS is still needed since the performance of the neural electrodes is limited by the body's response to the implant. This review discusses the issues with DBS, such as placement of electrodes, foreign body response, and electrode degradation. The current solutions to these technical issues include modifications to electrode material, coatings, and geometry.     

The clinical efficacy of -DOPA and STN-DBS share a common marker: reduced GABA content in the motor thalamus

At odd with traditional views, effective sub-thalamic nucleus (STN) deep brain stimulation (DBS), in Parkinson''s disease (PD) patients, may increase the discharge rate of the substantia nigra pars reticulata and the internal globus pallidus (GPi), in combination with increased cyclic guanosine monophosphate (cGMP) levels. How these changes affect the basal ganglia (BG) output to the motor thalamus, the crucial structure conveying motor information to cortex, is critical. Here, we determined the extracellular GABA concentration in the ventral anterior nucleus (VA) during the first delivery of STN-DBS (n=10) or following levodopa (LD) (n=8). Both DBS and subdyskinetic LD reversibly reduced (−30%) VA GABA levels. A significant correlation occurred between clinical score and GABA concentration. By contrast, only STN-DBS increased GPi cGMP levels. Hence, STN-ON and MED-ON involve partially different action mechanisms but share a common target in the VA. These findings suggest that the standard BG circuitry, in PD, needs revision as relief from akinesia may take place, during DBS, even in absence of reduced GPi excitability. However, clinical amelioration requires fast change of thalamic GABA, confirming, in line with the old model, that VA is the core player in determining thalamo-cortical transmission.     

Impulsivities and Parkinson's Disease: Delay Aversion Is Not Worsened by Deep Brain Stimulation of the Subthalamic Nucleus

Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN) improves motor symptoms in Parkinson''s disease (PD), but can exert detrimental effects on impulsivity. These effects are especially related to the inability to slow down when high-conflict choices have to be made. However, the influence that DBS has on delay aversion is still under-investigated. Here, we tested a group of 21 PD patients on and off stimulation (off medication) by using the Cambridge Gamble Task (CGT), a computerized task that allows the investigation of risk-related behaviours and delay aversion, and psychological questionnaires such as the Barratt Impulsiveness Scale (BIS), the Sensitivity to Punishment and to Reward Questionnaire (SPSRQ), and the Quick Delay Questionnaire (QDQ). We found that delay aversion scores on the CGT were no higher when patients were on stimulation as compared to when they were off stimulation. In contrast, PD patients reported feeling more impulsive in the off stimulation state, as revealed by significantly higher scores on the BIS. Higher scores on the sensitivity to punishment subscale of the SPSRQ highlighted that possible punishments influence patients'' behaviours more than possible rewards. Significant correlations between delay aversion scores on the CGT and QDQ delay aversion subscale suggest that these two instruments can be used in synergy to reach a convergent validity. In conclusion, our results show that not all impulsivities are detrimentally affected by DBS of the STN and that the joint use of experimental paradigms and psychological questionnaires can provide useful insights in the study of impulsivity.     

Coordinate-Based Lead Location Does Not Predict Parkinson's Disease Deep Brain Stimulation Outcome

Background

Effective target regions for deep brain stimulation (DBS) in Parkinson''s disease (PD) have been well characterized. We sought to study whether the measured Cartesian coordinates of an implanted DBS lead are predictive of motor outcome(s). We tested the hypothesis that the position and trajectory of the DBS lead relative to the mid-commissural point (MCP) are significant predictors of clinical outcomes. We expected that due to neuroanatomical variation among individuals, a simple measure of the position of the DBS lead relative to MCP (commonly used in clinical practice) may not be a reliable predictor of clinical outcomes when utilized alone.

Methods

55 PD subjects implanted with subthalamic nucleus (STN) DBS and 41 subjects implanted with globus pallidus internus (GPi) DBS were included. Lead locations in AC-PC space (x, y, z coordinates of the active contact and sagittal and coronal entry angles) measured on high-resolution CT-MRI fused images, and motor outcomes (Unified Parkinson''s Disease Rating Scale) were analyzed to confirm or refute a correlation between coordinate-based lead locations and DBS motor outcomes.

Results

Coordinate-based lead locations were not a significant predictor of change in UPDRS III motor scores when comparing pre- versus post-operative values. The only potentially significant individual predictor of change in UPDRS motor scores was the antero-posterior coordinate of the GPi lead (more anterior lead locations resulted in a worse outcome), but this was only a statistical trend (p<.082).

Conclusion

The results of the study showed that a simple measure of the position of the DBS lead relative to the MCP is not significantly correlated with PD motor outcomes, presumably because this method fails to account for individual neuroanatomical variability. However, there is broad agreement that motor outcomes depend strongly on lead location. The results suggest the need for more detailed identification of stimulation location relative to anatomical targets.     

Effects of subthalamic nucleus stimulation on emotional prosody comprehension in Parkinson's disease

Background

Although impaired decoding of emotional prosody has frequently been associated with Parkinson''s disease (PD), to date only few reports have sought to explore the effect of Parkinson''s treatment on disturbances of prosody decoding. In particular, little is known about how surgical treatment approaches such as high frequency deep brain stimulation (DBS) affect emotional speech perception in patients with PD. Accordingly, the objective of this study was to evaluate the effect of subthalamic nucleus (STN) stimulation on prosody processing.

Methodology/Principal Findings

To this end the performance of 13 PD patients on three tasks requiring the decoding of emotional speech was assessed and subsequently compared to the performance of healthy control individuals. To delineate the effect of STN-DBS, all patients were tested with stimulators turned on as well as with stimulators turned off. Results revealed that irrespective of whether assessments were made “on” or “off” stimulation, patients'' performance was less accurate as compared to healthy control participants on all tasks employed in this study. However, while accuracy appeared to be unaffected by stimulator status, a facilitation of reactions specific to highly conflicting emotional stimulus material (i.e. stimulus material presenting contradicting emotional messages on a verbal and non-verbal prosodic level) was observed during “on” stimulation assessments.

Conclusion

In sum, presented results suggest that the processing of emotional speech is indeed modulated by STN-DBS. Observed alterations might, on the one hand, reflect a more efficient processing of highly conflicting stimulus material following DBS. However, on the other hand, given the lack of an improvement in accuracy, increased impulsivity associated with STN stimulation needs to be taken into consideration.     

经颅直流电刺激对帕金森病伴快速眼动相睡眠行为障碍患者认知功能及神经功能的影响

摘要 目的：探讨经颅直流电刺激对帕金森病伴快速眼动相睡眠行为障碍患者认知功能及神经功能的影响。方法：选择2018年9月-2019年9月在我院接受治疗的69例帕金森病伴快速眼动相睡眠行为障碍患者,采用随机数表法分为电刺激组（n=35）和对照组（n=34）。对照组给予常规抗帕金森病治疗,观察组在对照组的基础上给予经颅直流电刺激治疗。比较两组临床疗效、蒙特利尔认知评估量表（MoCA）、自主神经症状量表（SCOPA-AUT）、睡眠情况、汉密尔顿抑郁量表(HAMD)、Epworth嗜睡量表（ESS）评分、匹兹堡睡眠指数（PSQI）、帕金森氏病综合评分量表（UPDRS）变化情况。结果：治疗后,电刺激组有效率91.43%（32/35）较对照组70.59%（24/34）显著升高,差异显著（P<0.05）;治疗前,电刺激组与对照组之间认知功能及神经功能结果无差异;治疗后,电刺激组与对照组MoCA均随着时间的推移均呈上升趋势,且电刺激组上升程度较较组更低,SCOPA-AUT均随着时间的推移均呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）;治疗前,电刺激组与对照组之间临床睡眠情况结果无差异;治疗后,电刺激组与对照组总睡眠时间、睡眠效率均随着时间的推移均呈上升趋势,且电刺激组上升程度较对照组更低,醒觉指数均随着时间的推移呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）;治疗前,电刺激组与对照组之间抑郁、嗜睡情况无差异;治疗后,电刺激组与对照组抑郁、嗜睡均随着时间的推移均呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）;治疗前,电刺激组与对照组之间PSQI、UPDRS评分无差异;治疗后,电刺激组与对照组PSQI、UPDRS评分均随着时间的推移均呈下降趋势,且电刺激组下降程度较对照组更低（P<0.05）。结论：在帕金森病伴快速眼动相睡眠行为障碍患者中应用经颅直流电刺激效果显著,可有效改善认知功能及神经功能水平。     

Pathogenic Mutation in VPS35 Impairs Its Protection against MPP+ Cytotoxicity

Parkinson''s disease primarily results from progressive degeneration of dopaminergic neurons in the substantia nigra. Both neuronal toxicants and genetic factors are suggested to be involved in the disease pathogenesis. The mitochondrial toxicant 1-methyl-4-phenylpyridinium (MPP⁺) shows a highly selective toxicity to dopaminergic neurons. Recent studies indicate that mutation in the vacuolar protein sorting 35 (vps35) gene segregates with Parkinson''s disease in some families, but how mutation in the vps35 gene causes dopaminergic cell death is not known. Here, we report that enhanced VPS35 expression protected dopaminergic cells against MPP⁺ toxicity and that this neuroprotection was compromised by pathogenic mutation in the gene. A loss of neuroprotective functions contributes to the pathogenesis of VPS35 mutation in Parkinson''s disease.     

美多芭联合息宁对帕金森病患者症状波动 及便秘的影响

目的评价美多芭联合息宁分服对帕金森病患者症状波动和便秘的影响。方法选取我院帕金森病患者104例,随机分为分服组与对照组各52例。分服组患者采用美多芭联合息宁治疗,对照组患者单纯采用美多芭治疗。在患者入组时、治疗第4周和治疗第8周时分别比较两组患者日记记录的"开"和"关"时间以及帕金森病统一评分量表Ⅲ(UPDRS-Ⅲ)、PAC-SYM评分和PDQ-39评分结果。结果治疗后两组患者均延长了"开"时间,缩短"关"时间。分服组在治疗第4周和第8周时延长"开"时间、缩短"关"时间情况优于对照组,差异均有统计学意义(均P0.05)。治疗后两组患者UPDRS-Ⅲ评分均有所改善。治疗第4周时分服组患者UPDRS-Ⅲ评分、PAC-SYM评分与对照组比较差异无统计学意义(均P0.05);治疗第8周时分服组患者UPDRS-Ⅲ和PAC-SYM评分均低于对照组,差异有统计学意义(均P0.05)。两组患者治疗后PDQ-39评分均降低,治疗第4周时分服组患者PDQ-39评分与对照组相比差异无统计学意义(P0.05);治疗第8周时分服组患者PDQ-39评分低于对照组,差异有统计学意义(P0.05)。结论美多芭联合息宁分服对帕金森病患者症状波动和便秘的改善均优于单用美多芭治疗,能提高患者生活质量,值得临床推广。     

基于益生菌治疗帕金森病的研究进展

帕金森病是常见的神经退行性疾病,其发病原因至今尚未明确,目前的治疗方法价格昂贵、效果差且副作用大。帕金森病患者常见胃肠道功能障碍,帕金森病和肠道菌群之间的关联已得到实验证实,患者有望通过益生菌改善肠道菌群达到治疗的目的。工程益生菌的出现使得人们可以按照自己的意愿改造益生菌,提高其稳定性和靶向性,展现出其特有的应用潜力。本文将从益生菌治疗帕金森病的研究现状出发,阐述益生菌治疗帕金森病的可能机制,进一步分析工程益生菌治疗帕金森病的可行性,为该疾病的安全治疗提供新的思路。     

盐酸普拉克索联合美多巴对老年帕金森病的临床疗效及对运动功能的影响

目的:研究盐酸普拉克索联合美多巴对老年帕金森病的临床疗效及对运动功能的影响。方法:选择2014年3月~2015年8月在我院进行诊治的老年帕金森病患者210例,随机分为观察组和对照组,对照组给予美多巴,观察组给予盐酸普拉克索联合美多巴,比较两组的临床疗效,治疗前后运动功能、生活质量的变化情况和不良反应的发生情况。结果:观察组的治疗有效率为85.71%,明显高于对照组的65.71%(P0.05);治疗12周后,观察组UPDRS评分与治疗前和对照组相比均明显降低(P0.05);治疗12周后,观察组生理、心理、独立性、社会关系和环境等方面的评分与治疗前和对照组相比均明显升高(P0.05);两组间恶心、呕吐、开关现象、精神症状等不良反应发生率相比无明显差异(P0.05)。结论:盐酸普拉克索联合美多巴对老年帕金森病疗效显著,能明显改善运动功能,且用药安全,值得推广应用。     

Development of an Alpha-synuclein Based Rat Model for Parkinson's Disease via Stereotactic Injection of a Recombinant Adeno-associated Viral Vector

In order to study the molecular pathways of Parkinson''s disease (PD) and to develop novel therapeutic strategies, scientific investigators rely on animal models. The identification of PD-associated genes has led to the development of genetic PD models. Most transgenic α-SYN mouse models develop gradual α-SYN pathology but fail to display clear dopaminergic cell loss and dopamine-dependent behavioral deficits. This hurdle was overcome by direct targeting of the substantia nigra with viral vectors overexpressing PD-associated genes. Local gene delivery using viral vectors provides an attractive way to express transgenes in the central nervous system. Specific brain regions can be targeted (e.g. the substantia nigra), expression can be induced in the adult setting and high expression levels can be achieved. Further, different vector systems based on various viruses can be used. The protocol outlines all crucial steps to perform a viral vector injection in the substantia nigra of the rat to develop a viral vector-based alpha-synuclein animal model for Parkinson''s disease.     

文拉法辛联合认知行为疗法治疗帕金森病抑郁、认知功能障碍的临床疗效评价

目的:探讨文拉法辛联合认知行为疗法治疗帕金森病(PD)抑郁、认知功能障碍的临床疗效和安全性。方法:选择我院收治的60例PD合并抑郁、认知功能障碍患者并将其随机分为三组,分别为对照组(单用文拉法辛治疗),联合奥氮平组(文拉法辛联合奥氮平),联合认知行为疗法组(文拉法辛联合认知行为疗法),每组20例,于治疗前及治疗后4、8周末采用汉密尔顿抑郁量表(HAMD)进行抑郁程度评定,简易精神状态评价量表(MMSE)和事件相关电位(event-related potentials,ERPs)P300进行认知功能评定。结果:治疗4、8周时,三组的HAMD评分均较治疗前有不同程度下降,P300潜伏期较治疗前有不同程度缩短,P300波幅、MMSE评分有不同程度升高(P0.05),联合奥氮平组和联合认知行为疗法组HAMD评分较对照组明显下降,P300潜伏期较对照组明显缩短,P300波幅、MMSE评分明显升高(P0.05),联合认知行为疗法组HAMD评分较联合奥氮平组明显下降,P300潜伏期明显缩短,P300波幅、MMSE评分明显升高(P0.05)。三组均无特殊不良反应。结论:文拉法辛联合认知行为疗法治疗PD抑郁、认知功能障碍疗效确切,能显著改善患者抑郁症状,提高患者的认知功能,疗效较单用文拉法辛或文拉法辛联合奥氮平治疗更好,且安全性高。     

Deep brain stimulation amplitude alters posture shift velocity in Parkinson’s disease

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is now widely used to alleviate symptoms of Parkinson’s disease (PD). The specific aim of this study was to identify posture control measures that may be used to improve selection of DBS parameters in the clinic and this was carried out by changing the DBS stimulation amplitude. A dynamic posture shift paradigm was used to assess posture control in 4 PD STN-DBS subjects. Each subject was tested at 4 stimulation amplitude settings. Movements of the center of pressure and the position of the pelvis were monitored and several quantitative indices were calculated. The presence of any statistically significant changes in several normalized indices due to reduced/no stimulation was tested using the one-sample t test. The peak velocity and the average movement velocity during the initial and mid phases of movement towards the target posture were substantially reduced. These results may be explained in terms of increased akinesia and bradykinesia due to altered stimulation conditions. Thus, the dynamic posture shift paradigm may be an effective tool to quantitatively characterize the effects of DBS on posture control and should be further investigated as a tool for selection of DBS parameters in the clinic.     

Response of Human Thalamic Neurons to High-Frequency Stimulation

Thalamic deep brain stimulation (DBS) is an effective treatment for tremor, but the mechanisms of action remain unclear. Previous studies of human thalamic neurons to noted transient rebound bursting activity followed by prolonged inhibition after cessation of high frequency extracellular stimulation, and the present study sought to identify the mechanisms underlying this response. Recordings from 13 thalamic neurons exhibiting low threshold spike (LTS) bursting to brief periods of extracellular stimulation were made during surgeries to implant DBS leads in 6 subjects with Parkinson''s disease. The response immediately after cessation of stimulation included a short epoch of burst activity, followed by a prolonged period of silence before a return to LTS bursting. A computational model of a population of thalamocortical relay neurons and presynaptic axons terminating on the neurons was used to identify cellular mechanisms of the observed responses. The model included the actions of neuromodulators through inhibition of a non-pertussis toxin sensitive K⁺ current (I_KL), activation of a pertussis toxin sensitive K⁺ current (I_KG), and a shift in the activation curve of the hyperpolarization-activated cation current (I_h). The model replicated well the measured responses, and the prolonged inhibition was associated most strongly with changes in I_KG while modulation of I_KL or I_h had minimal effects on post-stimulus inhibition suggesting that neuromodulators released in response to high frequency stimulation are responsible for mediating the post-stimulation bursting and subsequent long duration silence of thalamic neurons. The modeling also indicated that the axons of the model neurons responded robustly to suprathreshold stimulation despite the inhibitory effects on the soma. The findings suggest that during DBS the axons of thalamocortical neurons are activated while the cell bodies are inhibited thus blocking the transmission of pathological signals through the network and replacing them with high frequency regular firing.     

Therapeutic Subthalamic Nucleus Deep Brain Stimulation Reverses Cortico-Thalamic Coupling during Voluntary Movements in Parkinson's Disease

Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted treatment for patients experiencing the motor complications of Parkinson''s disease (PD). While its successes are becoming increasingly apparent, the mechanisms underlying its action remain unclear. Multiple studies using radiotracer-based imaging have investigated DBS-induced regional changes in neural activity. However, little is known about the effect of DBS on connectivity within neural networks; in other words, whether DBS impacts upon functional integration of specialized regions of cortex. In this work, we report the first findings of fMRI in 10 subjects with PD and fully implanted DBS hardware receiving efficacious stimulation. Despite the technical demands associated with the safe acquisition of fMRI data from patients with implanted hardware, robust activation changes were identified in the insula cortex and thalamus in response to therapeutic STN DBS. We then quantified the neuromodulatory effects of DBS and compared sixteen dynamic causal models of effective connectivity between the two identified nodes. Using Bayesian model comparison, we found unequivocal evidence for the modulation of extrinsic (between region), i.e. cortico-thalamic and thalamo-cortical connections. Using Bayesian model parameter averaging we found that during voluntary movements, DBS reversed the effective connectivity between regions of the cortex and thalamus. This casts the therapeutic effects of DBS in a fundamentally new light, emphasising a role in changing distributed cortico-subcortical interactions. We conclude that STN DBS does impact upon the effective connectivity between the cortex and thalamus by changing their sensitivities to extrinsic afferents. Furthermore, we confirm that fMRI is both feasible and is tolerated well by these patients provided strict safety measures are adhered to.     

The epigenetic component of the brain response to electromagnetic stimulation in Parkinson's Disease patients: A literature overview

Modulations of epigenetic machinery, namely DNA methylation pattern, histone modification, and non‐coding RNAs expression, have been recently included among the key determinants contributing to Parkinson's Disease (PD) aetiopathogenesis and response to therapy. Along this line of reasoning, a set of experimental findings are highlighting the epigenetic‐based response to electromagnetic (EM) therapies used to alleviate PD symptomatology, mainly Deep Brain Stimulation (DBS) and Transcranial Magnetic Stimulation (TMS). Notwithstanding the proven efficacy of EM therapies, the precise molecular mechanisms underlying the brain response to these types of stimulations are still far from being elucidated. In this review we provide an overview of the epigenetic changes triggered by DBS and TMS in both PD patients and neurons from different experimental animal models. Furthermore, we also propose a critical overview of the exposure modalities currently applied, in order to evaluate the technical robustness and dosimetric control of the stimulation, which are key issues to be carefully assessed when new molecular findings emerge from experimental studies. Bioelectromagnetics. 39:3–14, 2018. © 2017 Wiley Periodicals, Inc.     

Neuroprotective Effects of Tetramethylpyrazine against Dopaminergic Neuron Injury in a Rat Model of Parkinson's Disease Induced by MPTP

Parkinson''s disease (PD) is the second most prevalent progressive neurodegenerative disease. Although several hypotheses have been proposed to explain the pathogenesis of PD, apoptotic cell death and oxidative stress are the most prevalent mechanisms. Tetramethylpyrazine (TMP) is a biological component that has been extracted from Ligusticum wallichii Franchat (ChuanXiong), which exhibits anti-apoptotic and antioxidant roles. In the current study, we aimed to investigate the possible protective effect of TMP against dopaminergic neuron injury in a rat model of Parkinson''s disease induced by MPTP and to elucidate probable molecular mechanisms. The results showed that TMP could notably prevent MPTP-induced dopaminergic neurons damage, reflected by improvement of motor deficits, enhancement of TH expression and the content of dopamine and its metabolite, DOPAC. We observed MPTP-induced activation of mitochondrial apoptotic death pathway, evidenced by up-regulation of Bax, down-regulation of Bcl-2, release of cytochrome c and cleavage of caspase 3, which was significantly inhibited by TMP. Moreover, TMP could prevent MPTP-increased TBARS level and MPTP-decreased GSH level, indicating the antioxidant role of TMP in PD model. And the antioxidant role of TMP attributes to the prevention of MPTP-induced reduction of Nrf2 and GCLc expression. In conclusion, in MPTP-induced PD model, TMP prevents the down-regulation of Nrf2 and GCLc, maintaining redox balance and inhibiting apoptosis, leading to the attenuation of dopaminergic neuron damage. The effectiveness of TMP in treating PD potentially leads to interesting therapeutic perspectives.