Journal of Neural Transmission最新文献

{"title":"Comparative efficacy of Mucuna pruriens and conventional levodopa in Parkinson's disease: a randomized controlled trial on pharmacokinetics and clinical perspectives from Asia.","authors":"Thanatat Boonmongkol, Onanong Phokaewvarangkul, Sornkanok Vimolmangkang, Thitima Wattanavijitkul, Virunya Komenkul, Roongroj Bhidayasiri","doi":"10.1007/s00702-025-02914-2","DOIUrl":"https://doi.org/10.1007/s00702-025-02914-2","url":null,"abstract":"<p><p>Levodopa remains central to Parkinson's disease (PD) treatment, but long-term use can cause motor complications, highlighting the need for additional therapies. Mucuna pruriens (MP), a natural source of levodopa, shows potential in managing these complications. Further research is needed to compare its pharmacokinetics (PK) and clinical outcomes with traditional levodopa formulations. This randomised, single-blind, crossover trial compared the PK, clinical outcomes, and safety of MP powder against levodopa/benserazide dispersible tablets (Levodopa DT) in PD patients with motor complications. Twelve participants were recruited to receive either 30 g of MP powder or two 100/25 levodopa DT in separate sessions with a two-week washout between sessions. Key PK parameters (AUC, Cmax, Tmax, and t_½) were measured. Clinical assessments used standard rating scales and adverse events were recorded. Data from 11 participants were analysed after one withdrawal. MP powder demonstrated significantly higher overall drug exposure, with a geometric mean AUC_0-∞ of 12,424.81 compared to 7981.69 ng·h/mL for levodopa DT. The geometric mean ratio was 155.67% (90% CI 134.59-180.04), exceeding the bioequivalence acceptance range of 80-125%. However, the two treatments exhibited similar Tmax and t₁/₂ values, indicating comparable rates of absorption and elimination. Clinically, MP provided a longer ON state without dyskinesia-232.2 min versus 161.8 min for levodopa DT (p = 0.01). Mild and transient adverse events, such as nausea and dizziness, were more frequently associated with MP. MP offers superior drug exposure and extends the ON state without increasing dyskinesia, positioning it as a promising alternative to synthetic levodopa for managing motor symptoms. These findings support MP's potential role in alleviating motor complications in PD treatment.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: The centenarian blueprint: lessons in defying Parkinson's disease.","authors":"Roongroj Bhidayasiri, Ikuko Aiba, Masahiro Nomoto","doi":"10.1007/s00702-025-02900-8","DOIUrl":"10.1007/s00702-025-02900-8","url":null,"abstract":"","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep brain stimulation in progressive supranuclear palsy: a dead-end story? A narrative review.","authors":"Gabriele Bellini, Giulia Di Rauso, Lorenzo Fontanelli, Elena Benevento, Lucrezia Becattini, Daniela Frosini, Roberto Ceravolo, Eleonora Del Prete","doi":"10.1007/s00702-025-02904-4","DOIUrl":"https://doi.org/10.1007/s00702-025-02904-4","url":null,"abstract":"<p><p>Progressive supranuclear palsy (PSP) is a rare, debilitating neurodegenerative disorder that significantly impairs both motor and cognitive functions. Current pharmacological treatments offer only transient symptomatic relief, driving interest in the past in alternative therapeutic strategies such as deep brain stimulation. Deep brain stimulation (DBS), known for its success in treating motor symptoms of Parkinson's disease, has been explored as a possible symptomatic treatment for PSP, considering the pedunculopontine nucleus (PPN), involved in motor control and postural stability, as a promising target for deep brain stimulation in PSP. However, its complex anatomy and the clinical variability of PSP complicate the prediction and generalization of the effectiveness of DBS. The present review examines the existing studies in the literature about DBS in PSP patients. Some studies highlighted modest benefits in motor symptoms, while others reported variable outcomes and inherent risks of the procedure. Generally, patients with a parkinsonism predominant phenotype have shown some subjective or clinical improvements in gait and balance when subjected to low-frequency stimulation. While DBS of the PPN holds promise for ameliorating gait and balance of PSP, current evidence does not yet establish clear criteria for ideal candidates, nor does it provide overwhelmingly supportive results in favor of PPN-DBS in PSP patients. Without any further systematic study is not possible to define accurate candidate selection parameters and understand long-term outcomes and safety profiles.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic innovations for the symptomatic treatment of Parkinson's disease: focus on technology-based therapies.","authors":"Jeryl Ritzi T Yu, Avery Kundrick, Enrique C Panganiban, Michelle Ann Sy, Saar Anis, Hubert H Fernandez","doi":"10.1007/s00702-025-02915-1","DOIUrl":"https://doi.org/10.1007/s00702-025-02915-1","url":null,"abstract":"<p><p>As Parkinson's disease (PD) progresses, patients experience motor fluctuations, which may manifest as motor and/or non-motor wearing off symptoms, delayed \"ON\" time, and/or levodopa-related dyskinesia. Deep brain stimulation (DBS) is an effective therapy but may not be suitable for all patients due to factors such as premorbid conditions age, or accessibility. We review technology-based therapeutic innovations for PD: infusion therapies and novel non-invasive neuromodulation methods using the following databases: PubMed, Cochrane, and Science Direct. Infusion therapies such as percutaneous (LCIG, LECIG) and subcutaneous options (ND0612, foslevodopa-foscarbidopa, CSAI) demonstrate significant benefits in reducing OFF time and enhancing ON time without troublesome dyskinesias. However, vigilance is required for procedural and skin adverse events. Neuromodulation approaches such as auricular, vagus nerve, and galvanic vestibular stimulation, as well as whole-body vibration, showed promising benefits in freezing of gait (FOG) and tremor. Infusion and non-invasive neuromodulation therapies provide additional treatment options for patients with refractory motor and non-motor symptoms and may be an alternative for those who experience limitations of traditional dopaminergic therapies and are not candidates for neurosurgical interventions.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world experience with continuous subcutaneous foslevodopa/foscarbidopa infusion: insights and recommendations.","authors":"Thomas Koeglsperger, Emir Berberovic, Christian Dresel, Sebastian Haferkamp, Jan Kassubek, Rahel Müller, Christian Oehlwein, Sebastian Paus, Peter Paul Urban","doi":"10.1007/s00702-025-02911-5","DOIUrl":"https://doi.org/10.1007/s00702-025-02911-5","url":null,"abstract":"<p><p>Traditional advanced therapies in Parkinson's disease (PD) with motor fluctuations and dyskinesias like continuous apomorphine infusion (CSAI), levodopa-carbidopa intestinal gel (LCIG), levodopa-carbidopa entacapone intestinal gel (LECIG), or deep brain stimulation (DBS) have played a central role in managing therapy-related complications. Recently, continuous subcutaneous foslevodopa/foscarbidopa infusion (CSFLI) has emerged as a novel therapeutic option. This manuscript provides insights from one year of real-world experience with CSFLI, addressing critical questions that clinicians face when selecting the most appropriate therapy for advanced PD. Our discussion centers on key considerations for patient selection, exploring which individuals may benefit more from CSFLI compared to other device-aided therapies. We highlight CSFLI's advantages in flexibility and ease of use but also consider limitations, particularly its side effects, such as skin-related issues. Recommendations are presented on how to prevent and manage these adverse effects to maximize patient compliance and therapeutic success. Additionally, the paper examines strategies for optimizing concurrent oral medications when combined with CSFLI, providing guidance on balancing pump infusion with necessary adjunctive oral treatments.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical characterization of Tau protein changes and amyloid dynamics in a novel non-transgenic rat model of tauopathy.","authors":"Lea Langer Horvat, Ena Španić Popovački, Mirjana Babić Leko, Klara Zubčić, Maja Mustapić, Patrick R Hof, Goran Šimić","doi":"10.1007/s00702-025-02909-z","DOIUrl":"https://doi.org/10.1007/s00702-025-02909-z","url":null,"abstract":"<p><p>In this study, we further characterized a non-transgenic model of tauopathy by examining tau protein changes using ELISA and Western blot upon inoculation of human tau oligomers (TO) and human tau synthetic pre-formed fibrils (TF) into the medial entorhinal cortex of Wistar rats. Our analyses showed that inoculation with TO did not significantly alter the ratio of phosphorylated tau at AT8 epitopes (pSer202/pThr205) to total tau protein in the hippocampus and entorhinal cortex, but only resulted in a decrease of phosphorylation at AT100 epitopes (pThr212/pSer214). As we previously observed an increase in AT8 immunostaining in both regions, this suggests method-dependent conformational alterations. In contrast, eleven months after inoculation, TF caused significant AT8 and PHF-1 (pSer396/pSer404) epitope-specific changes in tau phosphorylation in the hippocampus, but not in the entorhinal cortex, reflecting a more advanced stage of Alzheimer's disease (AD)-like changes compared to TO. Importantly, amyloid plaques appeared as early as four months post-inoculation with TO, preceding significant phosphorylation changes of tau, thus indicating that amyloid probably facilitates early tau seeding and spreading. This was corroborated by the observed dynamic changes in Aβ_1-42 levels in cerebrospinal fluid, with initial decreases followed by increases, similar to patterns seen in transgenic mouse models of AD and in AD patients. Altogether, these findings lead us to conclude that changes in tau protein induce amyloid changes and vice versa, which is actually what defines AD as a unique neurodegenerative disease.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antinociceptive properties of intravesical/needle-free administration of abobotulinumtoxinA in a rodent model of chronic visceral pain: in vivo and histological evidence.","authors":"Céline Augé, Mathieu Vogt, Vincent Martin, Stéphane Lezmi, Xavier Gamé, Philippe Lluel, Jacquie Maignel","doi":"10.1007/s00702-025-02906-2","DOIUrl":"https://doi.org/10.1007/s00702-025-02906-2","url":null,"abstract":"<p><p>While interstitial cystitis along with bladder pain syndrome (IC/BPS) is still poorly treated, published clinical evidence suggests that onabotulinumtoxinA (natural botulinum neurotoxin type A (BoNT/A)) intradetrusor injections is efficient in IC/BPS. However, as bladder instillation could be a safer and more convenient administration route, we aimed to investigate the effect of BoNT/A needle-free administration in an IC/BPS rodent model. Cyclophosphamide (CYP) was used to induce IC/BPS in rats. The resulting symptoms mimicked the main key features of human non-ulcerative IC/BPS. AbobotulinumtoxinA (aboBoNT-A) or reference compounds used in the clinic were delivered as a single intravesical administration into the bladder via the urethra. Visceral allodynia and hyperalgesia were assessed at the abdominal level with von Frey filaments before and after bladder pain induction. The levels of BoNT/A-cleaved SNAP25 (c-SNAP25), total SNAP25 (SNAP25^N-ter), beta-3 tubulin and CGRP in bladders were also quantified using immunohistochemistry (IHC), as well as the histopathological lesions. AboBoNT-A was well tolerated up to 30 U/rat. Allodynia and hyperalgesia were significantly decreased after aboBoNT-A dosing, with higher efficacy compared to references. c-SNAP25 IHC levels were low and similar in the detrusor for the 3 aboBoNT-A groups. Neither CYP or aboBoNT-A induced any change in the amount of SNAP25, beta-3 tubulin or CGRP. Some CYP-induced histopathological lesions showed a trend in improvement under aboBoNT-A. AboBoNT-A displayed analgesic properties that could translate into better therapies for visceral pain. Interestingly, intravesical (needle-free) administration seems like a promising and reproducible route for botulinum toxin therapy in patients with IC/BPS.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-motor fluctuations in Parkinson's disease: frequency and clinical correlate.","authors":"Baig Ilyas Mirza Mujahid, Vikram V Holla, Nitish Kamble, Ravi Yadav, Pramod Kumar Pal, Rohan R Mahale","doi":"10.1007/s00702-025-02908-0","DOIUrl":"https://doi.org/10.1007/s00702-025-02908-0","url":null,"abstract":"<p><p>Non-motor symptoms (NMS) occur in 60-97% of Parkinson's disease (PD) patients. NMS show fluctuations over the course of the day referred to as non-motor fluctuations (NMF). To assess the frequency, severity, predictors and effect of the NMF on the quality of life in PD patients. This was a cross-sectional, hospital based, single-centre study. A total of 150 patients with PD were recruited. NMF was assessed using the MDS-Non-motor rating scale (MDS-NMS) and the Non-motor fluctuation assessment questionnaire (NoMoFA). The mean age at presentation and age at onset was 51.3 ± 10.8 years and 44.6 ± 11.1 years respectively and male predominance (75.3%). The mean duration of parkinsonism was 5.3 ± 3.7 years. Motor fluctuations (MF) were seen in 97 patients. A total of 143 patients (95.3%) had at least single NMS. Depression, cognition and pain was the most common NMS domain. NMF was seen in 57 patients (39.8%). NMF occurred in 50.5% in PD patients with MF. Pain was the most frequent NMS which showed NMF followed by fatigue, anxiety and depression. Pain had greater degree of change from ON to OFF period as compared to other NMS domains. NMF was associated with longer disease duration, higher levodopa dose and longer levodopa intake, greater motor severity, MF, higher NMS burden and poor quality of life. NMF is seen in association with MF. Pain, anxiety, depression and fatigue was the common NMS showing NMF. Pain had a large degree of fluctuation in the severity.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress in lockdown: exploring the interplay and effects of cortisol and psychological distress in parent-child dyads.","authors":"Alexe Bilodeau-Houle, Félix Duplessis-Marcotte, Catherine Raymond, Rachel Primiani, Marie-France Marin","doi":"10.1007/s00702-025-02898-z","DOIUrl":"https://doi.org/10.1007/s00702-025-02898-z","url":null,"abstract":"<p><p>During the COVID-19 pandemic, some children experienced psychological distress. Moreover, pandemic-related stressors were associated with changes in hair cortisol concentrations (HCC) in youth. Research has shown that parental distress influenced children's well-being during the pandemic, but it remains unclear whether parental distress is associated with children's HCC during the pandemic. Furthermore, as some preliminary evidence suggests that children's HCC may predict their emotional response to the pandemic, it is essential to assess whether children's HCC provides insight into their susceptibility to developing symptoms associated with stress-related psychopathologies. The present study aimed to (1) examine the association between parental pandemic-related distress and children's HCC; (2) investigate the moderating role of parental distress on the association between parent and child HCC; and (3) explore the association between children's HCC and their distress longitudinally. In June 2020, 71 parent-child (8-15 y/o) dyads provided a hair sample to assess pre-pandemic HCC (December 2019-March 2020) and pandemic HCC (March-June 2020) in Quebec, Canada. Post-traumatic stress, anxiety, depression, and stress symptoms were also assessed in dyads every three months from June 2020 to March 2021. Results showed that parental stress symptoms and HCC were positively associated with children's HCC during the pandemic. Moreover, children's pre-pandemic and pandemic HCC were independently negatively associated with children's anxiety symptoms during the pandemic. These results provide evidence of an association between parental physiological and psychological stress and their children's HCC during the pandemic and suggest that HCC may help identify youth at risk of developing anxiety symptoms during chronic stressful events.</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Botulinum toxin effects on biochemical biomarkers related to inflammation-associated head and neck chronic conditions: a systematic review of clinical research.","authors":"Ines Novo Pereira, Sara Durão, Haidar Hassan, Ana Cristina Braga, André Mariz Almeida, Ana Cristina Manso, Ricardo Faria-Almeida, Giancarlo De la Torre Canales","doi":"10.1007/s00702-024-02869-w","DOIUrl":"https://doi.org/10.1007/s00702-024-02869-w","url":null,"abstract":"<p><p>Botulinum toxin type A (BoNT) has emerged as a potential alternative to conventional therapies to many debilitating chronic diseases characterised by inflammatory states. However, the biological rationale remains ambiguous. Our review aimed to systematically assessed which biochemical biomarkers have been reported in clinical research to evaluate BoNT analgesic and mood-lifting effects in head and neck chronic conditions related to inflammation. We searched databases and registries between inception and September 29, 2023. Of the nine included studies, there were concerns about risk of bias for six studies. The leading biomarker with five studies was the calcitonin gene-related peptide (CGRP), followed by serotonin with two studies. Oxidative stress biomarkers were only reported in one study. Several important players in inflammatory processes and different immune cell classes have been evaluated in four studies. There was only one trial measuring changes in beta Tubulin and SNAP-25, and another study evaluating cutaneous neuropeptide substance-P. After BoNT, a significant effect was reported in six studies, including decrease in plasma levels of CGRP in chronic migraine and trigeminal neuralgia; serotonin decrease when collected from human tears in refractory intractable dry eye disease and increase in peripheral blood platelets in painful cervical dystonia associated to depression and anxiety; decrease in plasma concentration of markers of oxidative damage to proteins and increase in biomarkers for antioxidant power; decrease in expression of gene sets involved in inflammatory pathways and immune cells classes in the periosteum and metalloproteinase-9 molecule in the tears. BoNT seems to affect some biomarkers present in chronic inflammatory conditions. However, the certainty evidence found was very low to moderate. This study is registered on PROSPERO (CRD42023432131).</p>","PeriodicalId":16579,"journal":{"name":"Journal of Neural Transmission","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}