Utility of diffusion tensor imaging and generalized q-sampling imaging for predicting short-term clinical effect of deep brain stimulation in Parkinson's disease.

PURPOSE: To assess whether diffusion tensor imaging (DTI) and generalized q-sampling imaging (GQI) metrics could preoperatively predict the clinical outcome of deep brain stimulation (DBS) in patients with Parkinson's disease (PD). METHODS: In this single-center retrospective study, from September 2021 to March 2023, preoperative DTI and GQI examinations of 44 patients who underwent DBS surgery, were analyzed. To evaluate motor functions, the Unified Parkinson's Disease Rating Scale (UPDRS) during on- and off-medication and Parkinson's Disease Questionnaire-39 (PDQ-39) scales were used before and three months after DBS surgery. The study population was divided into two groups according to the improvement rate of scales: ≥ 50% and < 50%. Five target regions, reported to be affected in PD, were investigated. The parameters having statistically significant difference were subjected to a receiver operating characteristic (ROC) analysis. RESULTS: Quantitative anisotropy (qa) values from globus pallidus externus, globus pallidus internus (qa_Gpi), and substantia nigra exhibited significant distributional difference between groups in terms of the improvement rate of UPDRS-3 scale during on-medication (p = 0.003, p = 0.0003, and p = 0.0008, respectively). In ROC analysis, the best parameter in predicting DBS response included qa_Gpi with a cut-off value of 0.01370 achieved an area under the ROC curve, accuracy, sensitivity, and specificity of 0.810, 73%, 62.5%, and 85%, respectively. Optimal cut-off values of ≥ 0.01864 and ≤ 0.01162 yielded a sensitivity and specificity of 100%, respectively. CONCLUSION: The imaging parameters acquired from GQI, particularly qa_Gpi, may have the ability to non-invasively predict the clinical outcome of DBS surgery.

Non-HLA angiotensin-type-1 receptor autoantibodies mediate the long-term loss of grafted neurons in Parkinson's disease models.

BACKGROUND: Clinical trials have provided evidence that transplants of dopaminergic precursors, which may be replaced by new in vitro stem cell sources, can integrate into the host tissue, and alleviate motor symptoms in Parkinson´s disease (PD). In some patients, deterioration of graft function occurred several months after observing a graft-derived functional improvement. Rejection of peripheral organs was initially related to HLA-specific antibodies. However, the role of non-HLA antibodies is now considered also relevant for rejection. Angiotensin-II type-1 receptor autoantibodies (AT1-AA) act as agonists of the AT1 receptors. AT1-AA are the non-HLA antibodies most widely associated with graft dysfunction or rejection after transplantation of different solid organs and hematopoietic stem cells. However, it is not known about the presence and possible functional effects of AT1-AA in dopaminergic grafts, and the effects of treatment with AT1 receptor blockers (ARBs) such as candesartan on graft survival. METHODS: In a 6-hydroxydopamine PD rat model, we studied the short-term (10 days)- and long-term (3 months) effects of chronic treatment with the ARB candesartan on survival of grafted dopaminergic neurons and microglial graft infiltration, as well as the effects of dopaminergic denervation and grafting on serum and CSF AT1-AA levels. The expression of AT1 receptors in grafted neurons was determined by laser capture microdissection. RESULTS: At the early period post-grafting, the number of grafted dopaminergic neurons that survived was not significantly different between treated and untreated hosts (i.e., control rats and rats treated with candesartan), probably because, just after grafting, other deleterious factors are predominant for dopaminergic cell death, such as mechanical trauma, lack of growth factors/nutrients and ischemia. However, several months post-grafting, we observed a significantly higher number of surviving dopaminergic neurons and a higher density of striatal dopaminergic terminals in the candesartan-treated group. For several months, grafted rats showed blood and cerebrospinal fluid levels of AT1-AA higher than normal controls, and also higher AT1-AA levels than non-grafted parkinsonian rats. CONCLUSIONS: The results suggest the use of ARBs such as candesartan in PD patients, particularly before and after dopaminergic grafts, and the need to monitor AT1-AA levels in PD patients, particularly in those candidates for dopaminergic grafting.

Effects of electroacupuncture on Sirt3/NLRP3/GSDMD signaling pathway in the substantia nigra of midbrain of rats with Parkinson's disease. / ç”µé’ˆå¯¹å¸•é‡‘æ£®ç— å¤§é¼ ä¸­è„‘é»‘è´¨Sirt3/NLRP3/GSDMD信号通路的影响.

OBJECTIVES: To observe the effects on tyrosine hydroxylase (TH), α-synaptic nucleoprotein (α-syn), sirtuin 3 (Sirt3), NOD-like receptor 3 (NLRP3) and gasdermin-D (GSDMD) in the substantia nigra of midbrain after electroacupuncture (EA) at "Fengfu"(GV16), "Taichong" (LR3) and "Zusanli" (ST36) in rats of Parkinson's disease (PD), so as to explore the mechanism of EA in treatment of PD. METHODS: SD rats were randomly divided into control, model and EA groups, with 10 rats in each group. The PD model was established by injecting rotenone into the neck and back, lasting 28 days. In the EA group, EA was applied to GV16, LR3 and ST36, 30 min each time, once daily, consecutively for 28 days. The open-field test was adopted to detect the total distance of autonomic movement of rats, and the pole climbing test was used to detect the body coordination ability of rats. In the substania nigra of midbrain, the positive expression of TH was determined using immunohistochemistry, the mRNA expression levels of α - syn, Sirt3, NLRP3 and GSDMD were detected by quantitative real-time fluorescence PCR, and the protein expression levels of NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and cysteinyl aspartate specific proteinase (Caspase)-1 were detected by Western blot. RESULTS: Compared with the control group, the total distance of autonomous movement was decreased (P<0.01) in the model group, and the score of pole climbing experiment was increased (P<0.01)；in the midbrain substantia nigra the positive expression of TH was decreased (P<0.01)；the mRNA expression level of Sirt3 was decreased (P<0.01), and those of α-syn, NLRP3 and GSDMD were increased (P<0.01)；while the protein expression levels of NLRP3, ASC and Caspase-1 were increased (P<0.01). When compared with the model group, the total distance of autonomous movement in open field experiment was increased (P<0.01) in the EA group and the score of pole climbing experiment was lower (P<0.05)；in the midbrain substantia nigra the positive expression of TH was increased (P<0.01)；the mRNA expression level of Sirt3 in the midbrain substantia nigra was increased (P<0.01), and those of α-syn, NLRP3 and GSDMD were reduced (P<0.01)；while the protein expression levels of NLRP3, ASC and Caspase-1 decreased (P<0.01, P<0.05). CONCLUSIONS: EA at "GV16" "LR3" and "ST36" can repair the neuronal injury, clear the abnormal accumulation of α-syn in the substania nigra of midbrain, and ameliorate mitochondrial damage in PD rats, which may be obtained by regulating Sirt3/NLRP3/GSDMD signaling pathway, so as to delay the occurrence and development of Parkinson's disease.

Overcoming Methodological Challenges for Advancing Stem Cell Therapies in Parkinson's Disease.

The quest for new and improved therapies for Parkinson's disease (PD) remains of paramount importance, despite previous trial failures. There is a current debate regarding the potential of stem cell research as a therapeutic approach for PD. The studies of dopaminergic fetal stem cells for PD treatment, their design, and the results of the initial surgical placebo-controlled trials were reviewed in this study. Some of the fundamental methodological challenges and possible strategies to resolve them were proposed. In this article, we argue that the most important impact lies in the proof-of-principle demonstrated by clinical trials for cell replacement strategies in reconstructing the human brain. While some researchers argue that the considerable technical challenges associated with cell therapies for PD warrant the discontinuation of further development using stem cells, we believe that the opposing viewpoints are instrumental in identifying a series of methodological misunderstandings. Here, we propose to expose key challenges to ensure the advancement of the field and unlock the potential of stem cell therapies in PD treatment. Overall, this review underscores the need for further research and innovation to overcome the hurdles in realizing the potential of stem cell-based therapies for PD.

Asleep versus awake GPi DBS surgery for Parkinson's disease: A systematic review and meta-analysis.

BACKGROUND: Patients with Parkinson's Disease (PD) who receive either asleep image-guided subthalamic nucleus deep brain stimulation (DBS) or the traditional awake technique have comparable motor outcomes. However, there are fewer studies regarding which technique should be chosen for globus pallidus internus (GPi) DBS. This systematic review and meta-analysis aims to compare the accuracy of lead placement and motor outcomes of asleep versus awake GPi DBS PD population. METHODS: We systematically searched PubMed, Embase, and Cochrane for studies comparing asleep vs. awake GPi DBS lead placement in patients with PD. Outcomes were spatial accuracy of lead placement, measured by radial error between intended and actual location, motor improvement measured using (UPDRS III), and postoperative stimulation parameters. Statistical analysis was performed with Review Manager 5.1.7. and OpenMeta [Analyst]. RESULTS: Three studies met inclusion criteria with a total of 247 patients. Asleep DBS was used to treat 192 (77.7 %) patients. Follow-up ranged from 6 to 48 months. Radial error was not statistically different between groups (MD -0.49 mm; 95 % CI -1.0 to 0.02; I2 = 86 %; p = 0.06), with a tendency for higher target accuracy with the asleep technique. There was no significant difference between groups in change on motor function, as measured by UPDRS III, from pre- to postoperative (MD 8.30 %; 95 % CI -4.78 to 21.37; I2 = 67 %, p = 0.2). There was a significant difference in postoperative stimulation voltage, with the asleep group requiring less voltage than the awake group (MD -0.27 V; 95 % CI -0.46 to - 0.08; I2 = 0 %; p = 0.006). CONCLUSION: Our meta-analysis indicates that asleep image-guided GPi DBS presents a statistical tendency suggesting superior target accuracy when compared with the awake standard technique. Differences in change in motor function were not statistically significant between groups.

Auditory oddball responses in the human subthalamic nucleus and substantia nigra pars reticulata.

The auditory oddball is a mainstay in research on attention, novelty, and sensory prediction. How this task engages subcortical structures like the subthalamic nucleus and substantia nigra pars reticulata is unclear. We administered an auditory OB task while recording single unit activity (35 units) and local field potentials (57 recordings) from the subthalamic nucleus and substantia nigra pars reticulata of 30 patients with Parkinson's disease undergoing deep brain stimulation surgery. We found tone modulated and oddball modulated units in both regions. Population activity differentiated oddball from standard trials from 200 ms to 1000 ms after the tone in both regions. In the substantia nigra, beta band activity in the local field potential was decreased following oddball tones. The oddball related activity we observe may underlie attention, sensory prediction, or surprise-induced motor suppression.

Making a difference: neurological support in the community.

Nearly 3 million people in the UK have a neurological condition; stroke, traumatic brain injury, Parkinson's disease, multiple sclerosis, brain tumour, motor neurone disease, among others - all affecting the person for the rest of their life. The NHS provides treatment at the onset of a condition but after that, there is a huge need for ongoing support. Research shows that those who are supported and know more about their condition are less likely to have to call on further in-hospital and GP care. There is enormous scope for improving the quality of life for those with neurological conditions. The right support-therapeutic and social-makes all the difference. The book, which this article is based on, shows how those with neurological conditions benefit from integrated ongoing support provided in the local community and self-help, and how lives can be improved. It explains good practice and encouraging methods in the support and treatment of those with life changing conditions.

Fundamentals of deep brain stimulation for Parkinson's disease in clinical practice: part 1.

Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.

Nas últimas três décadas, a estimulação cerebral profunda (ECP) se tornou um tratamento bem estabelecido para doença de Parkinson (DP) e outros transtornos do movimento. A eficácia a longo prazo na DP foi bem documentada para a melhora dos sintomas motores cardinais da DP e das complicações induzidas pelo uso do levodopa, como as flutuações motoras e as discinesias. O momento da seleção do paciente é crucial para se obter os benefícios ideais da ECP, antes que as complicações da DP se tornem irreversíveis. O objetivo desta primeira parte da revisão é examinar os conceitos fundamentais da ECP na prática clínica, discutindo os aspectos históricos, a seleção de pacientes, os potenciais efeitos da ECP nos sintomas motores e não motores da doença e o manejo prático dos pacientes após a cirurgia.

Long-term benefits of hematopoietic stem cell-based macrophage/microglia delivery of GDNF to the CNS in a mouse model of Parkinson's disease.

Glial cell line-derived neurotrophic factor (GDNF) protects dopaminergic neurons in various models of Parkinson's disease (PD). Cell-based GDNF gene delivery mitigates neurodegeneration and improves both motor and non-motor functions in PD mice. As PD is a chronic condition, this study aims to investigate the long-lasting benefits of hematopoietic stem cell (HSC)-based macrophage/microglia-mediated CNS GDNF (MMC-GDNF) delivery in an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model. The results indicate that GDNF treatment effectively ameliorated MPTP-induced motor deficits for up to 12 months, which coincided with the protection of nigral dopaminergic neurons and their striatal terminals. Also, the HSC-derived macrophages/microglia were recruited selectively to the neurodegenerative areas of the substantia nigra. The therapeutic benefits appear to involve two mechanisms: (1) macrophage/microglia release of GDNF-containing exosomes, which are transferred to target neurons, and (2) direct release of GDNF by macrophage/microglia, which diffuses to target neurons. Furthermore, the study found that plasma GDNF levels were significantly increased from baseline and remained stable over time, potentially serving as a convenient biomarker for future clinical trials. Notably, no weight loss, altered food intake, cerebellar pathology, or other adverse effects were observed. Overall, this study provides compelling evidence for the long-term therapeutic efficacy and safety of HSC-based MMC-GDNF delivery in the treatment of PD.

Anti-alpha synuclein and anti-tau immunotherapies: Can a cocktail approach work?

The hypothesis that neurodegenerative diseases are proteinopathies due to toxic effect of different underlying proteins, such as amyloid-beta and 3+4R-tau in Alzheimer's disease (AD) and alpha-synuclein in Parkinson's disease (PD), while still controversial is supported by several studies in the literature. This has led to conduct clinical trials attempting to reduce the load of these allegedly toxic proteins by immunotherapy, mostly but not solely based on antibodies against these proteins. Already completed clinical trials have ranged from initially negative results to recently partial positive outcomes, specifically for anti-amyloid antibodies in AD but also albeit to lesser degree for anti-synuclein antibodies in PD. Currently, there are several ongoing clinical trials in degenerative parkinsonisms with anti-synuclein approaches in PD and multiple system atrophy (MSA), as well as with anti-tau antibodies in 4R-tauopathies such as progressive supranuclear palsy (PSP). While it can be argued that expectations that part of these clinical trials will be positive can be hope or hype, it is reasonable to consider the future possibility of "cocktail" combination of different antibodies after the available experimental evidence of cross-talk between these proteins and neuropathological evidence of coexistence of these proteinopathies more frequently than expected by chance. Moreover, such "cocktail" approaches are widespread and accepted common practice in other fields such as oncology, and the complexity of neurodegenerative parkinsonisms makes reasonable the option for testing and eventually applying such combined approaches, should these prove useful separately, in the setting of patients with evidence of underlying concomitant proteinopathies, for example through biomarkers.

Survival and maturation of human induced pluripotent stem cell-derived dopaminergic progenitors in the parkinsonian rat brain is enhanced by transplantation in a neurotrophin-enriched hydrogel.

Objective.Although human induced pluripotent stem cell (iPSC)-derived cell replacement for Parkinson's disease has considerable reparative potential, its full therapeutic benefit is limited by poor graft survival and dopaminergic maturation. Injectable biomaterial scaffolds, such as collagen hydrogels, have the potential to address these issues via a plethora of supportive benefits including acting as a structural scaffold for cell adherence, shielding from the host immune response and providing a reservoir of neurotrophic factors to aid survival and differentiation. Thus, the aim of this study was to determine if a neurotrophin-enriched collagen hydrogel could improve the survival and maturation of iPSC-derived dopaminergic progenitors (iPSC-DAPs) after transplantation into the rat parkinsonian brain.Approach.Human iPSC-DAPs were transplanted into the 6-hydroxydopamine-lesioned striatum either alone, with the neurotrophins GDNF and BDNF, in an unloaded collagen hydrogel, or in a neurotrophin-loaded collagen hydrogel.Post-mortem, human nuclear immunostaining was used to identify surviving iPSC-DAPs while tyrosine hydroxylase immunostaining was used to identify iPSC-DAPs that had differentiated into mature dopaminergic neurons.Main results.We found that iPSC-DAPs transplanted in the neurotrophin-enriched collagen hydrogel survived and matured significantly better than cells implanted without the biomaterial (8 fold improvement in survival and 16 fold improvement in dopaminergic differentiation). This study shows that transplantation of human iPSC-DAPs in a neurotrophin-enriched collagen hydrogel improves graft survival and maturation in the parkinsonian rat brain.Significance.The data strongly supports further investigation of supportive hydrogels for improving the outcome of iPSC-derived brain repair in Parkinson's disease.

Bridging the Gap: Local Field Potentials Offer a Peek Into the Brain of a Person With Parkinson Disease.

Clinically available deep brain recordings in patients with Parkinson disease (PD) offer insights into disease mechanisms and create a pathway for personalized treatment strategies. This case illustrates the transformative potential of recordings of neuronal firing in the form of local field potentials (LFPs) by detailing a patient's clinical trajectory for 6 months after deep brain stimulation (DBS) surgery to treat their PD symptoms. LFPs, obtained easily in clinic with a tablet interface to measure and track brain rhythms across the disease course, enriched the patient's clinical picture. Specifically, strong beta peaks were captured at initial programming, and, as the beta peaks diminished over the course of optimizing settings, symptoms improved. These signals may also reveal insights into the neural dynamics of PD such as hypersynchrony in basal ganglia circuitry. Furthermore, the ability to record chronically may unlock new understanding of neuronal dysfunction in PD, possibly enabling future adaptive DBS. In conclusion, identification, tracking, and modulation of LFPs correlated with subjective and objective clinical improvement in the case presented. The use of neurophysiologic signals in the future may lead to therapeutic innovations for our patients with PD.

Statistical segmentation model for accurate electrode positioning in Parkinson's deep brain stimulation based on clinical low-resolution image data and electrophysiology.

BACKGROUND: Deep Brain Stimulation (DBS), applying chronic electrical stimulation of subcortical structures, is a clinical intervention applied in major neurologic disorders. In order to achieve a good clinical effect, accurate electrode placement is necessary. The primary localisation is typically based on presurgical MRI imaging, often followed by intra-operative electrophysiology recording to increase the accuracy and to compensate for brain shift, especially in cases where the surgical target is small, and there is low contrast: e.g., in Parkinson's disease (PD) and in its common target, the subthalamic nucleus (STN). METHODS: We propose a novel, fully automatic method for intra-operative surgical navigation. First, the surgical target is segmented in presurgical MRI images using a statistical shape-intensity model. Next, automated alignment with intra-operatively recorded microelectrode recordings is performed using a probabilistic model of STN electrophysiology. We apply the method to a dataset of 120 PD patients with clinical T2 1.5T images, of which 48 also had available microelectrode recordings (MER). RESULTS: The proposed segmentation method achieved STN segmentation accuracy around dice = 0.60 compared to manual segmentation. This is comparable to the state-of-the-art on low-resolution clinical MRI data. When combined with electrophysiology-based alignment, we achieved an accuracy of 0.85 for correctly including recording sites of STN-labelled MERs in the final STN volume. CONCLUSION: The proposed method combines image-based segmentation of the subthalamic nucleus with microelectrode recordings to estimate their mutual location during the surgery in a fully automated process. Apart from its potential use in clinical targeting, the method can be used to map electrophysiological properties to specific parts of the basal ganglia structures and their vicinity.

How to manage catatonia, Parkinson and dementia in ICU.

PURPOSE OF REVIEW: The rising prevalence of neurodegenerative and mental disorders, combined with the challenges posed by their frailty, has presented intensivists with complex issues in the intensive care unit (ICU). This review article explores specific aspects of care for patients with catatonia, Parkinson's disease (PD), and dementia within the context of the ICU, shedding light on recent developments in these fields. RECENT FINDINGS: Catatonia, a neuropsychiatric syndrome with potentially life-threatening forms, remains underdiagnosed, and its etiologies are diverse. PD patients in the ICU present unique challenges related to admission criteria, dopaminergic treatment, and respiratory care. Dementia increases the risk of delirium. Delirium is associated with long-term cognitive impairment and dementia. SUMMARY: While evidence is lacking, further research is needed to guide treatment for ICU patients with these comorbidities.

[The role of occupational therapy in Parkinson's disease]. / La place de l'ergothérapie dans la maladie de Parkinson.

Occupational therapy works with Parkinson's sufferers and their caregivers to help them maintain or resume their activities of daily living and their independence, by recommending environmental adaptations, technical aids, compensation strategies and functional training.

[Parkinson's disease: intrinsically palliative care]. / La maladie de Parkinson, une prise en soins intrinsèquement palliative.

Multidimensional, chronic, progressive and incurable, Parkinson's disease is, by definition, a palliative disease, and this from the moment of diagnosis. This vision, relatively new to neurology, calls for a paradigm shift, as well as a dual medical-paramedical and home-hospital alliance. This approach allows us to better understand the specificities of Parkinson's disease and its treatments in terms of palliative issues.

Effects of subthalamic nucleus deep brain stimulation using different frequency programming paradigms on axial symptoms in advanced Parkinson's disease.

BACKGROUND: In advanced Parkinson's disease (PD), axial symptoms are common and can be debilitating. Although deep brain stimulation (DBS) significantly improves motor symptoms, conventional high-frequency stimulation (HFS) has limited effectiveness in improving axial symptoms. In this study, we investigated the effects on multiple axial symptoms after DBS surgery with three different frequency programming paradigms comprising HFS, low-frequency stimulation (LFS), and variable-frequency stimulation (VFS). METHODS: This study involved PD patients who had significant preoperative axial symptoms and underwent bilateral subthalamic nucleus (STN) DBS. Axial symptoms, motor symptoms, medications, and quality of life were evaluated preoperatively (baseline). One month after surgery, HFS was applied. At 6 months post-surgery, HFS assessments were performed, and HFS was switched to LFS. A further month later, we conducted LFS assessments and switched LFS to VFS. At 8 months after surgery, VFS assessments were performed. RESULTS: Of the 21 PD patients initially enrolled, 16 patients were ultimately included in this study. Regarding HFS, all axial symptoms except for the Berg Balance Scale (p < 0.0001) did not improve compared with the baseline (all p > 0.05). As for LFS and VFS, all axial symptoms improved significantly compared with both the baseline and HFS (all p < 0.05). Moreover, motor symptoms and medications were significantly better than the baseline (all p < 0.05) after using LFS and VFS. Additionally, the quality of life of the PD patients after receiving LFS and VFS was significantly better than at the baseline and with HFS (all p < 0.0001). CONCLUSION: Our findings indicate that HFS is ineffective at improving the majority of axial symptoms in advanced PD. However, both the LFS and VFS programming paradigms exhibit significant improvements in various axial symptoms.

Immunotherapy: An emerging treatment option for neurodegenerative diseases.

Accumulation of misfolded proteins and protein aggregates leading to degeneration of neurons is a hallmark of several neurodegenerative diseases. Therapy mostly relies on symptomatic relief. Immunotherapy offers a promising approach for the development of disease-modifying routes. Such strategies have shown remarkable results in oncology, and this promise is increasingly being realized for neurodegenerative diseases in advanced preclinical and clinical studies. This review highlights cases of passive and active immunotherapies in Parkinson's and Alzheimer's diseases. The reasons for success and failure, wherever available, and strategies to cross the blood-brain barrier, are discussed. The need for conditional modulation of the immune response is also reflected on.

Sham surgery for the trialing of cell-based therapies to the CNS may not be necessary.

Sham surgery is often required for cell therapies adopting a randomized placebo-controlled double-blinded trial design. Using the case of dopamine neuron therapy for Parkinson's disease, we argue that alternative trial designs should be considered instead, for several reasons relating to ethics, patient burden, ease of unblinding, and cost.

Investigating the neuroprotective potential of rAAV2-PCBP1-EGFP gene therapy against a 6-OHDA-induced model of Parkinson's disease.

OBJECTIVES: Previous studies have suggested a potential link between poly(rC)-binding protein 1 (PCBP1) and neurodegenerative diseases, including Parkinson's disease (PD). However, the precise role of PCBP1 in the pathogenesis of PD remains unclear. Therefore, the main objective of this study was to investigate the neuroprotective effects of PCBP1 in a PD model. METHODS: To evaluate the neuroprotective potential of PCBP1, we conducted cell count assays and observed the expression of heat shock protein 70 (HSP70) in SH-SY5Y cells exposed to 6-OHDA-induced neurotoxicity. Additionally, we utilized recombinant adeno-associated virus (rAAV2) vectors encoding PCBP1 or EGFP, which were injected into the rat striatum. After 2 weeks of vector or saline injection, 6-OHDA was administered to the rat striatum. Behavioral assessments using the open field test (OFT) were performed weekly for 7 weeks. At the seventh week after 6-OHDA injection, immunohistochemistry and protein expression analyses were conducted in the three groups. RESULTS: The results indicated that PCBP1 treatment significantly reduced the proliferation of 6-OHDA-induced SH-SY5Y cells. Additionally, in surviving cells, overexpression of PCBP1 enhanced the expression of HSP70. Similarly, rAAV2 vectors effectively delivered PCBP1 into the brain, resulting in sustained expression of rAAV2-PCBP1-EGFP. In the OFT, PCBP1 exhibited significant improvements in behavioral abnormalities and reduced anxiety in the PD model rats (p < .01). Moreover, PCBP1 effectively prevented the decrease of tyrosine hydroxylase and HSP70 expression in the lesioned side induced by 6-OHDA (p < .01). Consistent with expectations, PCBP1 efficiently protected against cell death caused by 6-OHDA (p < .01). CONCLUSIONS: In conclusion, our findings provide compelling evidence for the beneficial effects of PCBP1 in the PD model, suggesting that PCBP1 could be a potential therapeutic target for PD.