Non-motor Symptoms Research Articles

Personalized Visualization of the Gestures of Parkinson’s Disease Patients with Virtual Reality

Parkinson’s disease is a neurological disorder characterized by motor and non-motor symptoms. Assessment methods, despite the many years of existence of the disease, lack individualized visualization. On the other hand, virtual reality promises immersion and realism. In this paper, we develop an integrated system for visualizing the gestures of Parkinson’s disease patients in a virtual reality environment. With this application, clinicians will have information about the unique motor patterns and challenges they must address in each individual patient’s case, while the collected data can travel and be easily and instantly visualized in any location. At the beginning of this research, the current terms of immersive technologies in conjunction with data visualization and Parkinson’s disease are described. Through an extensive systematic literature review, the technological developments in the field of Parkinson’s data visualization are presented. The findings of the review lead to the experimental procedure and implementation of the application. The conclusions drawn from this work fuel future extensions on the contribution of immersive technologies to various diseases.

Clinical Characteristics of Patients with De Novo Parkinson's Disease and a Positive Family History.

Background/Objectives: A family history of Parkinson's disease (PD) is an important risk factor for developing PD. Because only a few studies have investigated the clinical characteristics of PD patients based on family history, this study compared the clinical characteristics of PD patients with and without a family history of PD. Methods: The study involved 356 patients with de novo PD. The data on the patients' PD family histories were obtained from the patients and their caregivers. Motor and non-motor PD symptoms were assessed using the appropriate scales. Results: Out of the 356 PD patients, 26 (7.3%) had a family history of PD. Compared with patients without a family history of PD, those with a family history of PD tended to be younger at diagnosis (67.9 years vs. 62.2 years, respectively; p = 0.009) and exhibited significantly more severe rigidity (p = 0.036). Motor subtype was not different between the PD patients with and without a family history. PD patients with a family history experienced significantly fewer falls/cardiovascular symptoms within the Non-Motor Symptoms Scale domains (p = 0.001) compared to their counterparts, although this was not statistically significant upon adjusting for age (p = 0.119). Conclusions: In de novo PD patients, having a family history of PD is associated with a younger age at diagnosis and more severe rigidity.

Trial to assess the tolerability of using felodipine to upregulate autophagy as a treatment of Huntington’s disease (FELL-HD): a phase II, single-centre, open-label, dose-finding trial protocol

IntroductionHuntington’s disease (HD) is an autosomal dominant neurodegenerative disorder that presents with a progressive movement disorder along with cognitive and psychiatric problems. It is caused by a Cytosine-adenin-guanine (CAG) expansion...

Prevalence and impact of sleep-related breathing disorder in multiple system atrophy patients: a cross-sectional study and meta-analysis.

Sleep-related breathing disorder (SRBD) is a prevalent non-motor symptom in multiple system atrophy (MSA). However, the reported prevalence of SRBD in MSA from different studies has shown inconsistency. Additionally, only one study has examined the impact of SRBD on both motor and non-motor symptoms in MSA. Cross-sectional study of 66 patients with probable MSA from China. SRBD was ascertained with polysomnography (PSG). All the MSA individuals were assessed using the Epworth Sleepiness Scale (ESS), Unified Multiple-System Atrophy Rating Scale (UMSARS), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), the Mini-mental State Examination (MMSE), Non-Motor Symptoms Scale (NMSS), and Pittsburgh Sleep Quality Index (PSQI). Moreover, a meta-analysis was conducted by searching studies related to MSA and SRBD in PubMed, Web of Science, Embase, and Cochrane databases. Data were pooled as necessary to calculate prevalence of SBRD with 95% confidence intervals (CI). Our study included 66 patients with MSA, 52 of whom had a diagnosis of SRBD (78.8%). There were no significant differences between the MSA with SRBD and without SRBD groups on the age, sex, disease onset, disease duration, UMSARS I, II, and IV, the NMSS, the HAMA, HAMD, the ESS the FSS, the MMSE, and the PSQI scales. However, MSA patients with SRBD having a significant higher obstructive apnea index and percentage of snoring during sleep than MSA patients without SRBD [10.0 (4.1-10.6) vs. 0.1 (0-0.3), and 8.3 (5.1-12.2) vs. 4.2 (0-7.5)]. Also, between the two groups, the mean and minimum oxygen concentrations during sleep were lower in MSA patients with SRBD than in those without SRBD [93.7 (93-95) vs. 95.5 (95.8-97), p = 0.001] and [83.9 (81.2-89.0) vs. 90.3 (89.8-93.3), p = 0.000]. The primary search strategy identified 701 articles, with 10 meeting the inclusion criteria. The overall prevalence of SRBD in a combined sample of 295 MSA patients was found to be 60.5% (95% CI, 43.2-76.5%). Further analysis revealed that the prevalence of SRBD in MSA patients in Asia was 79.2% (95% CI, 54.7-96.3%), which was higher than that in Europe (41.6, 95% CI, 32-51.5%). The study found a prevalence of 78.8% of SRBD in MSA patients, with a notably higher prevalence in Asia compared to Europe. The majority of SRBD cases in MSA were attributed to obstructive apnea. Furthermore, the presence of SRBD did not show a significant impact on the motor and non-motor symptoms of MSA patients.

Constipation is associated with emotional and cognitive impairment in patients with Parkinson’s disease: A clinical and brain functional study

ObjectiveConstipation frequently occurs in patients with Parkinson’s disease (PD) and may be related to cognitive and emotional disorders. The aim of this study is to investigate the clinical and brain functional characteristics of patients with PD presenting with constipation. MethodsThe motor and non-motor symptoms of patients with PD were evaluated, and a resting-state functional magnetic resonance imaging (RS-fMRI) study was conducted based on propensity score matching. Alterations in brain function were analyzed using regional homogeneity (ReHo) and functional connectivity (FC). ResultsCompared with patients without constipation (PD-NC group), patients with constipation (PD-C group) had more serious motor and non-motor symptoms (including cognitive and emotional disorders along with visual hallucinations). Further, emotional and cognitive disorders were correlated with the occurrence of constipation in patients with PD. Compared with the PD-NC group, the PD-C group showed a reduced ReHo of the right insula and bilateral orbitofrontal cortex (OFC), increased ReHo of the left postcentral gyrus, and enhanced FC between the right OFC and the left middle temporal gyrus (MTG) and middle occipital gyrus (MOG). Additionally, the activity of the OFC and insula was significantly correlated with the constipation, mood, and cognitive levels of patients with PD. ConclusionsConstipation in patients with PD is closely related to emotional and cognitive impairments, abnormal activity and FC of brain regions such as the right insula and bilateral OFC may play an important role in this.

Unveiling the link: hepatitis C virus and Parkinson’s disease

BackgroundParkinson disease (PD) is one of the disabling neurological disorders. The etiology of Parkinson disease is still unknown. Hepatitis C virus is one of the neurotropic viruses which is incriminated in the pathogenesis of Parkinson disease. Hepatitis C virus might affect the dopaminergic neurons, affecting the advancement of PD.MethodsThis study is observational, cross-sectional study done on 2 phases: one phase on PD patients without history of HCV and another phase on HCV patients with no history of PD. 104 PD patient were tested for HCV antibodies and 40 HCV patients with various grades of liver fibrosis were assessed for early pre-motor symptoms of parkinsonism.ResultsAmong patients with parkinsonism, HCV Abs testing was negative in all the studied patients. On the other hand, chronic HCV group included 40 patients, 27.5% were cirrhotic (11/40). Child C patients showed significantly higher percentages of non-motor parkinsonian symptoms, and regarding the HCV group, the majority (85%) of the patients show cognitive impairment, (27.5%) were at stage 1 of anxious mood, while half (50%) of the patients were at stage 1 of fatigue as evaluated by UPDRS Score. Cirrhosis was a significant factor for having non-motor (early) parkinsonism.ConclusionHere we show that advanced cirrhosis is associated with a variety of neurological symptoms including parkinsonian, which needs awareness for better preventive and therapeutic measures for early treatment of hepatitis avoiding the occurrence of cirrhosis, which can lead to parkinsonism.

Changes in the analgesic mechanism of oxytocin can contribute to hyperalgesia in Parkinson's disease model rats.

Pain is a major non-motor symptom of Parkinson's disease (PD). Alterations in the descending pain inhibitory system (DPIS) have been reported to trigger hyperalgesia in PD patients. However, the underlying mechanisms remain unclear. In the current study, dopaminergic nigrostriatal lesions were induced in rats by injecting 6-hydroxydopamine (6-OHDA) into their medial forebrain bundle. The neural mechanisms underlying changes in nociception in the orofacial region of 6-OHDA-lesioned rats was examined by injecting formalin into the vibrissa pad. The 6-OHDA-lesioned rats were seen to exhibit increased frequency of face-rubbing and more c-Fos immunoreactive (c-Fos-IR) cells in the trigeminal spinal subnucleus caudalis (Vc), confirming hyperalgesia. Examination of the number of c-Fos-IR cells in the DPIS nuclei [including the midbrain ventrolateral periaqueductal gray, the locus coeruleus, the nucleus raphe magnus, and paraventricular nucleus (PVN)] showed that 6-OHDA-lesioned rats exhibited a significantly lower number of c-Fos-IR cells in the magnocellular division of the PVN (mPVN) after formalin injection compared to sham-operated rats. Moreover, the 6-OHDA-lesioned rats also exhibited significantly lower plasma oxytocin (OT) concentration and percentage of oxytocin-immunoreactive (OT-IR) neurons expressing c-Fos protein in the mPVN and dorsal parvocellular division of the PVN (dpPVN), which secrete the analgesic hormone OT upon activation by nociceptive stimuli, when compared to the sham-operated rats. The effect of OT on hyperalgesia in 6-OHDA-lesioned rats was examined by injecting formalin into the vibrissa pad after intracisternal administration of OT, and the findings showed a decrease in the frequency of face rubbing and the number of c-Fos-IR cells in the Vc. In conclusion, these findings confirm presence of hyperalgesia in PD rats, potentially due to suppression of the analgesic effects of OT originating from the PVN.

Capturing subjective cognitive decline with a new combined index in low education patients with Parkinson's disease.

Subjective Cognitive Decline (SCD) refers to self-reported cognitive decline with normal global cognition. This study aimed to capture SCD among low educated patients with Parkinson's disease (PD) using a newly established indicator. We recruited 64 PD patients with low education levels (education ≤12 years) for the study. The presence of SCD was determined based on a Unified Parkinson's Disease Rating Scale Part I (1.1) score ≥ 1. Spearman analysis and multivariate binary logistic regression analyses were conducted to investigate factors associated with the PD-SCD group. The receiver operating characteristic (ROC) curve was used to evaluate the sensitivity and specificity of the new combined index. The prevalence of SCD in PD patients was 43.75%. Low educated PD-SCD patients had higher scores on the Non-Motor Symptoms Scale (NMSS), Parkinson's Fatigue Scale (PFS), Epworth Sleepiness Scale (ESS), as well as higher scores on the UPDRS-I and UPDRS-II, compared to PD patients without SCD. They also demonstrated poorer performance on the Montreal Cognitive Assessment (MoCA), particularly in the domains of executive abilities/attention/language. Multivariate binary regression confirmed the significant association between PD-SCD and MoCA-executive abilities/attention/language. Based on these findings, a combined index was established by summing the scores of MoCA-executive abilities, MoCA-attention, and MoCA-language. ROC analysis showed that the combined index could differentiate PD-SCD patients with an area under the curve (AUC) of 0.876. A score of 12 or less on the combined index had a sensitivity of 73.9% and a specificity of 76.2% for diagnosing PD-SCD. These low education patients with PD-SCD may exhibit potential PD-related pathological changes. It is important for clinicians to identify PD-SCD patients as early as possible. The newly combined index can help capture these low educated PD-SCD patients, with an AUC of 0.867, and is expected to assist clinicians in earlier identification and better management of PD patients.

Depression and Parkinson’s disease

Parkinson's disease is a progressive neurodegenerative disease with motor symptoms and non-motor impairments, including depression, observed in 2.7-90% of cases. Depression is frequently underestimated and diagnosed late due to its similarity with symptoms of Parkinson's disease, such as fatigue, sleep disturbances, hypomimia, etc. In approximately 25% of patients, depression precedes motor symptoms, which may indicate its connection with the pathogenesis of Parkinson's disease. The purpose of the study was to analyze current data on the pathophysiology, diagnosis, and treatment of depression in patients with Parkinson's disease. The study results have demonstrated that the pathophysiological mechanisms of depression in Parkinson's disease include neurodegeneration of dopaminergic, noradrenergic, and serotonergic neurons, neuroinflammation, and impaired neuroplasticity. For timely treatment, patients, especially those with changes in motor or non-motor symptoms, should be regularly examined. Treatment is based on a multimodal approach and includes the use of supportive psychotherapy and pharmacotherapy. Alternative methods such as exercise, cognitive behavioral therapy, transcranial magnetic stimulation, and electroconvulsive therapy are also being explored. Thus, treatment of patients with depression and Parkinson's disease requires an individualized approach. Further research into this problem is crucial to develop and improve patient management algorithms.

Construct, Face, and Predictive Validity of Parkinson's Disease Rodent Models.

Parkinson's disease (PD) is the second most common neurodegenerative disease globally. Current drugs only alleviate symptoms without halting disease progression, making rodent models essential for researching new therapies and understanding the disease better. However, selecting the right model is challenging due to the numerous models and protocols available. Key factors in model selection include construct, face, and predictive validity. Construct validity ensures the model replicates pathological changes seen in human PD, focusing on dopaminergic neurodegeneration and a-synuclein aggregation. Face validity ensures the model's symptoms mirror those in humans, primarily reproducing motor and non-motor symptoms. Predictive validity assesses if treatment responses in animals will reflect those in humans, typically involving classical pharmacotherapies and surgical procedures. This review highlights the primary characteristics of PD and how these characteristics are validated experimentally according to the three criteria. Additionally, it serves as a valuable tool for researchers in selecting the most appropriate animal model based on established validation criteria.

Genetic Polymorphisms in the HMGCR Gene and Associations with Cognitive Decline in Parkinson's Disease Patients.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by motor and non-motor symptoms including cognitive impairment and dementia. The etiopathogenesis of PD, as well as its protective and susceptibility factors, are still elusive. 3-Hydroxy-3-methyglutaryl coenzyme A reductase (HMGCR) is an enzyme regulating cholesterol synthesis. Single-nucleotide polymorphisms (SNPs) in the gene coding HMGCR have recently been correlated with the risk of Alzheimer's disease. Alternative splicing of exon 13 of the HMGCR transcript and its strongly associated HMGCR haplotype 7 (H7: rs17244841, rs3846662, rs17238540) may downregulate protein activity and cholesterol synthesis, with lower low-density lipoprotein cholesterol (LDL) levels associated with PD that may affect cognitive abilities. We genotyped three SNPs in the H7 HMGCR gene in 306 PD patients divided into three groups-without cognitive decline, with mild cognitive impairment (MCI), and with PD dementia-and in 242 healthy participants. A correlation between the rs17238540 genotype and PD susceptibility as well as a minor association between rs3846662 and cognitive status in PD patients was observed; however, the two-sided analysis of these groups did not reveal any significance. We observed a statistically significant elevated high-density lipoprotein cholesterol (HDL) plasma level in the minor allele carriers of rs17238540 and rs17244841 among PD patients. This study should be replicated in a larger population.

The pathogenesis and treatment of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disease that primarily affects middle-aged and older adults. Its incidence is second only to that of Alzheimer's disease. The primary source of clinical symptoms is the degradation and death of dopaminergic neurons in the substantia nigra-striatum. Patients mainly show motor symptoms such as static tremor, rigidity, bradykinesia and postural instability, and non-motor symptoms such as sensory disturbance, autonomic nervous dysfunction and mental cognitive impairment. There is no proven way to cure the disease or to slow its progression through neuroprotection, therefore treatment focuses mostly on treating symptoms. This study examines the shared pathophysiology of PD, which includes inflammation, abnormalities in protein handling, oxidative stress, and mitochondrial dysfunction. Next it discusses the available PD treatment options, which include standard medication therapy, promising surgical procedures, gene therapy, and new approaches to individualized PD care. The safety and usefulness of many treatments are still unknown, though. Hope that as life science and technology advance, the etiology of Parkinson's disease will become clearer and more dependable treatment options will be created to enhance sufferers' quality of life.

Burden of non-motor symptoms in Parkinson’s disease and atypical parkinsonism syndromes: A single-center cross-sectional comparison study

Burden of non-motor symptoms in Parkinson’s disease and atypical parkinsonism syndromes: A single-center cross-sectional comparison study

Upregulation of γ-synuclein in the prefrontal cortex and hippocampus following dopamine depletion: A study using the striatal 6-hydroxydopamine hemiparkinsonian rat model

Synucleins, including α-synuclein (α-syn), β-syn, and γ-syn, have been implicated in various synucleinopathies, notably Parkinson’s disease (PD), which has generated increased interest in understanding their roles. Although α-syn and β-syn have contrasting neuropathological consequences, the precise role of γ-syn remains unclear. This study validated non-motor symptoms, specifically anxiety-like behavior, along with the degradation of dopaminergic (DAergic) neurons in the nigrostriatal system and DAergic neurites in the prefrontal cortex and hippocampus of rats infused with striatal 6-hydroxydopamine (6-OHDA). Our study further investigated the alterations in γ-syn expression levels in the prefrontal cortices and hippocampi of these 6-OHDA–treated rats, aiming to establish foundational insights into the neuropathophysiology of DA depletion, a central feature of PD. Our findings revealed a significant increase in the expression of γ-syn mRNA and protein in these brain regions, in contrast to unaltered α- and β-syn expression levels. This suggests a distinct role of γ-syn within the neurobiological milieu under conditions of DA deficiency. Overall, our data shed light on the neurobiological changes observed in the hemiparkinsonian rat model induced with 6-OHDA, underscoring the potential significance of γ-syn in PD pathology.

Disease progression in Parkinson's disease patients with mild cognitive impairment: 5-year longitudinal study from the early Parkinson's disease longitudinal Singapore (PALS) cohort.

To investigate motor, non-motor and cognitive progression in early Parkinson's disease (PD) patients with Mild Cognitive Impairment (MCI). PD patients were recruited within 1 year of diagnosis and were classified into PD-MCI group and PD with normal cognition (PD-NC) group. H&Y staging scale, MDS-UPDRS part III were used to assess disease severity and motor progression. Non-motor symptom scale (NMSS) was used to evaluate the NMS progression. Cognitive progression was assessed from 5 cognitive domains. Annual progression changes in the longitudinal outcomes were examined via linear mixed model with random intercept effect. False discovery rate (FDR) method was performed to control for multiple testing comparison and q-value was calculated. We set the threshold of q-values as 0.1. A total of 205 PD patients, including 107 PD-MCI and 98 PD-NC patients were assessed prospectively over a 5-year period. PD-MCI patients, compared to PD-NC group, had a significantly higher progression rate in H&Y score (0.11 vs. 0.06, p=0.03, q=0.08), MDS-UPDRS motor score (3.11 vs. 1.90 p<0.001, q=0.06) and postural instability gait difficulty (PIGD) score (0.40 vs. 0.20, p=0.02, q=0.07). PD-MCI group also exhibited significantly faster deterioration in NMSS perceptual domain (PD-MCI vs. PD-NC: 0.38 vs. -0.04, p=0.01, q=0.06) and cognitive visuospatial domain (PD-MCI vs. PD-NC: 0.13 vs. -0.06, p=0.048, q=0.09) after adjustment for confounders and multiple comparisons. PD-MCI patients had faster decline in motor functions, visuo-perceptual and visuospatial performance. These findings provide a more comprehensive prognosis of PD-MCI, which could be helpful for clinician to manage PD-MCI patients.

Impact of the Anticholinergic Burden on Disease-Specific Symptoms in Parkinsonian Syndromes.

Background: Anticholinergic adverse effects pose a relevant threat to patients, in particular elderly and cognitively impaired patients. Patients with Parkinsonian syndromes are especially at risk from anticholinergic adverse effects due to the often-required complex drug therapy. Aims: The aim of this study was to evaluate the potential effect of the anticholinergic burden on motor and non-motor symptoms in Parkinson's disease and atypical Parkinsonian syndromes. Methods: This cross-sectional, monocentric retrospective data analysis included 151 patients with Parkinson's disease (PD), 63 with progressive supranuclear palsy (PSP), and 36 with multiple system atrophy (MSA). The anticholinergic burden of patients' medications was determined using two established scores: the Anticholinergic Drug Scale (ADS) and the German Anticholinergic Burden Scale (GABS). These scores were compared between the different diseases and correlated with several disease-specific scores. Results: Anticholinergic burden was higher in patients with PD, in particular, compared to PSP. In the PD group, anticholinergic burden showed a weak correlation with almost all analyzed clinical scores and the number of administered drugs. The UMSARS I and II showed a significant correlation with the anticholinergic burden in MSA patients. In general, the GABS-measured anticholinergic burden was significantly higher compared to the ADS-measured. Conclusions: The calculated anticholinergic burden affected motor and non-motor symptoms in patients with various Parkinsonian syndromes poorly. Since the GABS also contains basic anti-parkinsonian drugs, this score tended to overestimate the anticholinergic burden in patients with Parkinsonian syndromes and, therefore, seemed less appropriate for this application.

TECHNOLOGY-BASED EVALUATION IN PARKINSONISM

Parkinson's disease is a neurodegenerative disorder characterized by motor and non-motor symptoms that worsen over time. Today, traditional clinical assessment methods are used to monitor disease progression and evaluate treatment responses. However, these methods are subjective and may fail to measure specific conditions. In recent years, thanks to advances in wearable technologies, smart sensors, and data analysis, technology-based approaches to the assessment of patients with Parkinson's disease have gained more attention. With these technologies, objective data can be obtained by monitoring patients' daily activities, motor functions, and symptoms. Motor symptoms such as tremor severity, rigidity, bradykinesia, postural instabilities, freezing phenomenon, and motor parameters of speech impairment can be objectively measured through these technologies. Furthermore, the ability to remotely transmit these data allows patients to be assessed in their own homes and provides continuous feedback to healthcare professionals. This review highlights the importance and potential of technology-based assessment methods in Parkinson's patients and aims to guide future research.

L-theanine, the unique constituent of tea, improves neuronal survivability by curtailing inflammatory responses in MPTP model of Parkinson's disease

Discrete components of tea possess multitude of health advantages. Escalating evidence advocate a consequential association between habitual tea consumption and a subsided risk of Parkinson's disease (PD). l-theanine is a non-protein amino acid inherent in tea plants, which exhibits structural resemblance with glutamate, the copious excitatory neurotransmitter in brain. Neuromodulatory effects of l-theanine are evident from its competency in traversing the blood brain barrier, promoting a sense of calmness beyond enervation, and enhancing cognition and attention. Despite the multifarious reports on antioxidant properties of l-theanine and its potential to regulate brain neurotransmitter levels, it is obligatory to understand its exact contribution in ameliorating the pathophysiology of PD. In this study, MPTP-induced mouse model was established and PD-like symptoms were developed in test animals where an increasing dosage of l-theanine (5, 25, 50, 100 and 250 mg/kg) was intraperitoneally administered for 23 days. 50 and 100 mg/kg dosage of l-theanine alleviated motor impairment and specific non-motor symptoms in Parkinsonian mice. The dosage of 100 mg/kg of l-theanine also improved striatal dopamine and serotonin level and tyrosine-hydroxylase positive cell count in the substantia nigra. Most crucial finding of the study is the proficiency of l-theanine to diminish astroglial injury as well as nitric oxide synthesis, which suggests its possible credential to prevent neurodegeneration by virtue of its anti-inflammatory attribute.

Clinical characteristics and treatment of psychosis in Parkinson's disease: A narrative review.

Parkinson's disease (PD) is a chronic, progressive, neurodegenerative disorder whose clinical presentation consists of motor and non-motor signs and symptoms. Among the non-motor symptoms, psychosis can occur in the later stages of the disease. Psychosis in PD (PDP) is a common, complex, and significantly disabling disorder associated with poorer quality of life, accelerated cognitive decline, need for hospitalization or institutionalization, and mortality. Hallucinations are a significant symptom of PDP, sporadic at first but more frequent in the later course of the disease, and significantly disrupt daily activities. Appropriate and timely screening of psychotic manifestations is necessary for adequate therapeutic procedures. After the exclusion of comorbid conditions as a possible cause of psychosis, correction of antiparkinsonian therapy may be required, and if necessary, the introduction of antipsychotics. The latest therapeutic recommendations include the use of pimavanserin, if available, otherwise second-generation or atypical antipsychotics. Although PDP has long been recognized as a possible complication in the course of the disease, further clinical studies are needed to fully understand its etiopathogenesis and pathophysiological mechanisms.

Central Role of Hypothalamic Circuits for Acupuncture's Anti-Parkinsonian Effects.

Despite clinical data stretching over millennia, the neurobiological basis of the effectiveness of acupuncture in treating diseases of the central nervous system has remained elusive. Here, using an established model of acupuncture treatment in Parkinson's disease (PD) model mice, we show that peripheral acupuncture stimulation activates hypothalamic melanin-concentrating hormone (MCH) neurons via nerve conduction. We further identify two separate neural pathways originating from anatomically and electrophysiologically distinct MCH neuronal subpopulations, projecting to the substantia nigra and hippocampus, respectively. Through chemogenetic manipulation specifically targeting these MCH projections, their respective roles in mediating the acupuncture-induced motor recovery and memory improvements following PD onset are demonstrated, as well as the underlying mechanisms mediating recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, these MCH neurons constitute not only a circuit-based explanation for the therapeutic effectiveness of traditional acupuncture, but also a potential cellular target for treating both motor and non-motor PD symptoms.