{"title":"Neurodiversity and Autism Spectrum Disorder: An Ostriches' Head in the Sand?","authors":"Gerry Leisman","doi":"10.31083/j.jin2310186","DOIUrl":"https://doi.org/10.31083/j.jin2310186","url":null,"abstract":"","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"186"},"PeriodicalIF":2.5,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545846","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}
Xin Yu, Kang Wu, Yuanyuan Li, Chen Chen, Tianzhu Chen, Xinyue Shi, Zhongjian Tan, Yihuai Zou
{"title":"Dynamic Reorganization Patterns of Brain Modules after Stroke Reflecting Motor Function.","authors":"Xin Yu, Kang Wu, Yuanyuan Li, Chen Chen, Tianzhu Chen, Xinyue Shi, Zhongjian Tan, Yihuai Zou","doi":"10.31083/j.jin2310182","DOIUrl":"https://doi.org/10.31083/j.jin2310182","url":null,"abstract":"<p><strong>Objective: </strong>Advancements in neuroimaging technologies have significantly deepened our understanding of the neural physiopathology associated with stroke. Nevertheless, the majority of studies ignored the characteristics of dynamic changes in brain networks. The relationship between dynamic changes in brain networks and the severity of motor dysfunction after stroke needs further investigation. From the perspective of multilayer network module reconstruction, we aimed to explore the dynamic reorganization of the brain and its relationship with motor function in subcortical stroke patients.</p><p><strong>Methods: </strong>We recruited 35 healthy individuals and 50 stroke patients with unilateral limb motor dysfunction (further divided into mild-moderate group and severe group). Using dynamic multilayer network modularity analysis, we investigated changes in the dynamic modular reconfiguration of brain networks. Additionally, we assessed longitudinal clinical scale changes in stroke patients. Correlation and regression analyses were employed to explore the relationship between characteristic dynamic indicators and impairment and recovery of motor function, respectively.</p><p><strong>Results: </strong>We observed increased temporal flexibility in the Default Mode Network (DMN) and decreased recruitment of module reconfiguration in the Attention Network (AN), Sensorimotor Network (SMN), and DMN after stroke. We also observed reduced module loyalty following stroke. Additionally, correlation analysis showed that hyper-flexibility of the DMN was associated with better lower limb motor function performance in stroke patients with mild-to-moderate impairment. Regression analysis indicated that increased flexibility within the DMN and decreased recruitment coefficient within the AN may predict good lower limb function prognosis in patients with mild to moderate motor impairment.</p><p><strong>Conclusions: </strong>Our study revealed more frequent modular reconfiguration and hyperactive interaction of brain networks after stroke. Notably, dynamic modular remodeling was closely related to the impairment and recovery of motor function. Understanding the temporal module reconfiguration patterns in multilayer networks after stroke can provide valuable information for more targeted treatments.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"182"},"PeriodicalIF":2.5,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545841","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":"Key Synaptic Pathology in Autism Spectrum Disorder: Genetic Mechanisms and Recent Advances.","authors":"Yuan Zhang, Rui Tang, Zhi-Min Hu, Xi-Hao Wang, Xia Gao, Tao Wang, Ming-Xi Tang","doi":"10.31083/j.jin2310184","DOIUrl":"https://doi.org/10.31083/j.jin2310184","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions and verbal communication, accompanied by symptoms of restricted and repetitive patterns of behavior or interest. Over the past 30 years, the morbidity of ASD has increased in most areas of the world. Although the pathogenesis of ASD is not fully understood, it has been associated with over 1000 genes or genomic loci, indicating the importance and complexity of the genetic mechanisms involved. This review focuses on the synaptic pathology of ASD and particularly on genetic variants involved in synaptic structure and functions. These include <i>SHANK</i>, <i>NLGN</i>, <i>NRXN</i>, <i>FMR1</i>, and <i>MECP2</i> as well as other potentially novel genes such as <i>CHD8</i>, <i>CHD2</i>, and <i>SYNGAP1</i> that could be core elements in ASD pathogenesis. Here, we summarize several pathological pathways supporting the hypothesis that synaptic pathology caused by genetic mutations may be the pathogenic basis for ASD.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"184"},"PeriodicalIF":2.5,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545844","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}
Louis Negri, Patrick Oliver, Rebecca Mitchell, Lavanya Sinha, Jacob Kearney, Dominic Saad, Fernando R Nodal, Victoria M Bajo
{"title":"Optimization of the Operant Silent Gap-in-Noise Detection Paradigm in Humans.","authors":"Louis Negri, Patrick Oliver, Rebecca Mitchell, Lavanya Sinha, Jacob Kearney, Dominic Saad, Fernando R Nodal, Victoria M Bajo","doi":"10.31083/j.jin2310183","DOIUrl":"https://doi.org/10.31083/j.jin2310183","url":null,"abstract":"<p><strong>Background: </strong>In the auditory domain, temporal resolution is the ability to respond to rapid changes in the envelope of a sound over time. Silent gap-in-noise detection tests assess temporal resolution. Whether temporal resolution is impaired in tinnitus and whether those tests are useful for identifying the condition is still debated. We have revisited these questions by assessing the silent gap-in-noise detection performance of human participants.</p><p><strong>Methods: </strong>Participants were seventy-one young adults with normal hearing, separated into preliminary, tinnitus and matched-control groups. A preliminary group (n = 18) was used to optimise the silent gap-in-noise detection two-alternative forced-choice paradigm by examining the effect of the position and the salience of the gap. Temporal resolution was tested in case-control observational study of tinnitus (n = 20) and matched-control (n = 33) groups using the previously optimized silent gap-in-noise behavioral paradigm. These two groups were also tested using silent gap prepulse inhibition of the auditory startle reflex (GPIAS) and Auditory Brain Responses (ABRs).</p><p><strong>Results: </strong>In the preliminary group, reducing the predictability and saliency of the silent gap increased detection thresholds and reduced gap detection sensitivity (slope of the psychometric function). In the case-control study, tinnitus participants had higher gap detection thresholds than controls for narrowband noise stimuli centred at 2 and 8 kHz, with no differences in GPIAS or ABRs. In addition, ABR data showed latency differences across the different tinnitus subgroups stratified by subject severity.</p><p><strong>Conclusions: </strong>Operant silent gap-in-noise detection is impaired in tinnitus when the paradigm is optimized to reduce the predictability and saliency of the silent gap and to avoid the ceiling effect. Our behavioral paradigm can distinguish tinnitus and control groups suggesting that temporal resolution is impaired in tinnitus. However, in young adults with normal hearing, the paradigm is unable to objectively identify tinnitus at the individual level. The GPIAS paradigm was unable to differentiate the tinnitus and control groups, suggesting that operant, as opposed to reflexive, silent gap-in-noise detection is a more sensitive measure for objectively identifying tinnitus.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 10","pages":"183"},"PeriodicalIF":2.5,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545856","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}
Jaimie Barr, Robert Vangel, Prabesh Kanel, Stiven Roytman, Chatkaew Pongmala, Roger L Albin, Peter J H Scott, Nicolaas I Bohnen
{"title":"Topography of Cholinergic Nerve Terminal Vulnerability and Balance Self-Efficacy in Parkinson's Disease.","authors":"Jaimie Barr, Robert Vangel, Prabesh Kanel, Stiven Roytman, Chatkaew Pongmala, Roger L Albin, Peter J H Scott, Nicolaas I Bohnen","doi":"10.31083/j.jin2309178","DOIUrl":"https://doi.org/10.31083/j.jin2309178","url":null,"abstract":"<p><strong>Background: </strong>Postural instability and gait disturbances (PIGD) represent a significant cause of disability in Parkinson's disease (PD). Cholinergic system dysfunction has been implicated in falls in PD. The occurrence of falls typically results in fear of falling (FoF) that in turn may lead to poorer balance self-efficacy. Balance self-efficacy refers to one's level of confidence in their ability to balance while completing activities of daily living like getting dressed, bathing, and walking. Lower self-efficacy, or greater FoF during these activities is a function of motor, cognitive, and emotional impairments and may impact quality of life in PD. Unlike known cholinergic reduction, especially in the right lateral geniculate and caudate nuclei, little is known about the role of cholinergic transporters in FoF or mobility self-efficacy in PD.</p><p><strong>Methods: </strong>[<sup>18</sup>F]fluoroethoxybenzovesamicol ([<sup>18</sup>F]FEOBV) positron emission tomography (PET) studies were conducted to assess vesicular acetylcholine transporter (VAChT) expression in 126 patients with PD (male (m) = 95, female (f) = 31). Participants had a mean age of 67.3 years (standard deviation (SD) = 7.1) and median Hoehn Yahr stage of 2.5. Patients also completed the Short Falls Efficacy Scale (sFES-I) as a survey measure of concerns about falling. [<sup>18</sup>F]FEOBV data were processed in Statistical Parametric Mapping (SPM) using a voxel-wise regression model with sFES-I scores as the outcome measure.</p><p><strong>Results: </strong>Reduced [<sup>18</sup>F]FEOBV binding in tectum, metathalamic (lateral more than medial geniculate nuclei), thalamus proper, bilateral mesiotemporal (hippocampal, parahippocampal, fusiform gyri and fimbriae), and right cerebellar lobule VI significantly associated with higher sFES-I scores (<i>p</i> < 0.05, family-wise error (FWE) correction after Threshold-Free Cluster Enhancement (TFCE)).</p><p><strong>Conclusions: </strong>Unlike the more limited involvement of the brainstem-thalamic complex and caudate nuclei cholinergic topography associated with falls in PD, cholinergic reductions in the extended connectivity between the thalamic complex and the temporal limbic system via the fimbriae associates with FoF. Additional cholinergic changes were seen in the cerebellum. The temporal limbic system plays a role not only in episodic memory but also in spatial navigation, scene and contextual (<i>e.g.</i>, emotional) processing. Findings may augur novel therapeutic approaches to treat poor mobility self-efficacy in PD.</p><p><strong>Clinical trial registration: </strong>No: NCT02458430. Registered 18 March, 2015, https://www.</p><p><strong>Clinicaltrials: </strong>gov/study/NCT02458430; No: NCT05459753. Registered 01 July, 2022, https://www.</p><p><strong>Clinicaltrials: </strong>gov/study/NCT05459753.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 9","pages":"178"},"PeriodicalIF":2.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348289","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":"Abnormal Weakening of DNA Methylation around the <i>SLC6A1</i> Gene Promoter in Temporal Lobe Epilepsy.","authors":"Hua Tao, Zhengjuan Wu, Yang Liu, Xiaolu Zhang, Keshen Li, Xu Zhou","doi":"10.31083/j.jin2309181","DOIUrl":"10.31083/j.jin2309181","url":null,"abstract":"<p><strong>Background: </strong>The solute carrier (SLC) superfamily, which transports solutes across biological membranes, includes four members (SLC2A1, SLC6A1, SLC9A64, and SLC35A2) that have been linked to epilepsy. This study sought to examine the DNA methylation patterns near the promoters of these genes in temporal lobe epilepsy (TLE), as DNA methylation is a crucial epigenetic modification that can impact gene expression.</p><p><strong>Methods: </strong>The study comprised 38 individuals with TLE and 38 healthy controls. Methylation experiments were performed using peripheral blood, while demethylation experiments were carried out using SH-SY5Y cells with the DNA methylation inhibitor decitabine.</p><p><strong>Results: </strong>A significant difference was observed in the DNA methylation rate of <i>SLC6A1</i> between TLE patients and controls, with TLE patients showing a lower rate (4.81% vs. 5.77%, <i>p</i> = 0.0000), which remained significant even after Bonferroni correction (<i>p</i> = 0.0000). Based on the hypomethylated <i>SLC6A1</i> in TLE, a predictive model was established that showed promise in distinguishing and calibrating TLE. In the TLE group, there were differences in DNA methylation rates of <i>SLC6A1</i> between the young patients and the older controls (4.42% vs. 5.22%, <i>p</i> = 0.0004). A similar trend (<i>p</i> = 0.0436) was noted after adjusting for sex, age at onset, and drug response. In addition, the study found that DNA methylation had a silencing impact on the expression of the <i>SLC6A1</i> gene in SH-SY5Y cells, which were treated with decitabine at a set dose gradient.</p><p><strong>Conclusions: </strong>The evidence suggests that lower methylation of <i>SLC6A1</i> may stimulate transcription in TLE, however, further investigation is necessary to confirm the exact mechanism.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 9","pages":"181"},"PeriodicalIF":2.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348202","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}
Jing Li, Pei-Pei Liu, Yan Wang, Chong-Yang Ren, Mei Zhang
{"title":"Lectin YKL-40 Level and Telomere Length are Indicators of Insomnia Disorder.","authors":"Jing Li, Pei-Pei Liu, Yan Wang, Chong-Yang Ren, Mei Zhang","doi":"10.31083/j.jin2309180","DOIUrl":"10.31083/j.jin2309180","url":null,"abstract":"<p><strong>Objective: </strong>To explore the relationship between YKL-40 level, telomere length, and different subtypes of insomnia disorder.</p><p><strong>Methods: </strong>A total of 145 individuals suffering from insomnia were enrolled and divided into four groups according to the insomniac subtypes: difficulty initiating sleep, early morning awakening, difficulty maintaining sleep, and mixed symptoms. Eighty healthy controls were also collected at the same time. Peripheral leukocyte genomic DNA was extracted, relative telomere lengths were measured using the real-time quantitative polymerase chain reaction method, and YKL-40 levels were determined using enzyme-linked immunoassay. Logistic regression modeling was used to analyze the correlation between different insomnia subtypes, YKL-40 level, and telomere length.</p><p><strong>Results: </strong>People with telomere lengths in the lowest tertile were more likely to have trouble falling asleep (odds ratio (OR) 2.13, 95% confidence interval (CI) 1.22-3.63; <i>p</i> = 0.03) and had a higher frequency of mixed symptoms (OR 1.49, 95% CI 1.30-2.81; <i>p</i> = 0.04). People in the highest tertile of YKL-40 level had an increased chance of waking up early (OR 2.98, 95% CI 1.54-5.33; <i>p</i> = 0.01) and more mixed symptoms (OR 1.47, 95% CI 1.22-2.79; <i>p</i> = 0.02). Furthermore, using receiver operating characteristic curve analysis, the area under the curve of YKL-40 level and telomere length was 0.806 and 0.746, respectively.</p><p><strong>Conclusions: </strong>Telomere length in patients with difficulty initiating sleep and mixed symptoms was significantly shortened and the level of YKL-40 in people who have early morning awakening and mixed symptoms was significantly increased. Our findings provide the first evidence that leukocyte telomere length and YKL-40 level are individually linked to mixed symptoms.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 9","pages":"180"},"PeriodicalIF":2.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348218","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":"Unveiling Functional Biomarkers in Schizophrenia: Insights from Region of Interest Analysis Using Machine Learning.","authors":"Indranath Chatterjee, Lea Baumgärtner","doi":"10.31083/j.jin2309179","DOIUrl":"https://doi.org/10.31083/j.jin2309179","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia is a complex and disabling mental disorder that represents one of the most important challenges for neuroimaging research. There were many attempts to understand these basic mechanisms behind the disorder, yet we know very little. By employing machine learning techniques with age-matched samples from the auditory oddball task using multi-site functional magnetic resonance imaging (fMRI) data, this study aims to address these challenges.</p><p><strong>Methods: </strong>The study employed a three-stage model to gain a better understanding of the neurobiology underlying schizophrenia and techniques that could be applied for diagnosis. At first, we constructed four-level hierarchical sets from each fMRI volume of 34 schizophrenia patients (SZ) and healthy controls (HC) individually in terms of hemisphere, gyrus, lobes, and Brodmann areas. Second, we employed statistical methods, namely, <i>t</i>-tests and Pearson's correlation, to assess the group differences in cortical activation. Finally, we assessed the predictive power of the brain regions for machine learning algorithms using K-nearest Neighbor (KNN), Naive Bayes, Decision Tree (DT), Random Forest (RF), Support Vector Machines (SVMs), and Extreme Learning Machine (ELM).</p><p><strong>Results: </strong>Our investigation depicts promising results, obtaining an accuracy of up to 84% when applying Pearson's correlation-selected features at lobes and Brodmann region level (81% for Gyrus), as well as Hemispheres involving different stages. Thus, the results of our study were consistent with previous studies that have revealed some functional abnormalities in several brain regions. We also discovered the involvement of other brain regions which were never sufficiently studied in previous literature, such as the posterior lobe (posterior cerebellum), Pyramis, and Brodmann Area 34.</p><p><strong>Conclusions: </strong>We present a unique and comprehensive approach to investigating the neurological basis of schizophrenia in this study. By bridging the gap between neuroimaging and computable analysis, we aim to improve diagnostic accuracy in patients with schizophrenia and identify potential prognostic markers for disease progression.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 9","pages":"179"},"PeriodicalIF":2.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348290","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}
Tamás Oroszi, Wouter Huiting, Jan N Keijser, Csaba Nyakas, Marieke J G van Heuvelen, Eddy A van der Zee
{"title":"Whole-Body Vibration Affects Hippocampal Choline Acetyltransferase and Synaptophysin Expression and Improves Spatial Memory in Young Adult Mice.","authors":"Tamás Oroszi, Wouter Huiting, Jan N Keijser, Csaba Nyakas, Marieke J G van Heuvelen, Eddy A van der Zee","doi":"10.31083/j.jin2309173","DOIUrl":"10.31083/j.jin2309173","url":null,"abstract":"<p><strong>Background: </strong>Beneficial effects of whole-body vibration (WBV) on brain and musculoskeletal health in mice have been demonstrated, but underlying mechanisms remain relatively unrevealed. WBV improves attention and memory performance in mice, putatively through stimulation of the cholinergic system. Here, we investigated the effects of WBV on the septo-hippocampal cholinergic system.</p><p><strong>Methods: </strong>Young C57BL/6 mice (8 weeks old) were subjected to 10 min WBV/day (mechanical vibration: 30 Hz; ~0.1-μm peak-to-peak displacement), 5X/week for 5 weeks. In Experiment 1, choline acetyltransferase (ChAT)-immunoreactivity in the septum and hippocampus was analyzed either 2 or 24 h after the last WBV session. Pseudo-WBV-treated mice (same handling procedure as WBV, but no vibrations) served as controls. In Experiment 2, the longitudinal profile of ChAT-immunoreactivity was analyzed in the hippocampus after 1, 2, 3, 4, or 5 weeks of WBV. In addition, synaptophysin immunostaining was performed at either 2 and 5 weeks of WBV. Mice housed 1/cage during the entire experiment served as controls. The balance-beam test was used to monitor the functional impact of WBV. In Experiment 3, a Y-maze reference-memory test was performed after 5 weeks of WBV to obtain a functional cognitive outcome measure of WBV. Pseudo-WBV treated mice served as controls.</p><p><strong>Results: </strong>In Experiment 1, ChAT-immunoreactivity was significantly enhanced after the last WBV session of the 5-week period. This was found in the septum, Cornu Ammonis 1 (CA1), CA3, and dentate gyrus, and was dependent on layer and time-point (2 or 24 h). Experiment 2 revealed that, ChAT-immunoreactivity was lower after 2 weeks of WBV, whereas it was significantly higher after 5 weeks (similar to in Experiment 1). Immunostaining for synaptophysin, a marker for synaptic density, was also significantly higher after 5 weeks of WBV, but not significantly lower after 2 weeks, as was ChAT. WBV-treated groups performed significantly better than did controls on the balance beam from week 3 onwards. Experiment 3 showed that WBV-treated mice had better spatial-reference memory performance in the Y-maze test than did pseudo-WBV controls.</p><p><strong>Conclusions: </strong>Our results indicate that WBV stimulates the septo-hippocampal cholinergic system in a gradual and dynamic way that may contribute to improved spatial-memory performance. This finding suggests that WBV, by upregulation of the septo-hippocampal cholinergic system, may be considered a valuable therapeutic strategy to enhance brain functions in aging, neurodegenerative, and other brain diseases.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 9","pages":"173"},"PeriodicalIF":2.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348301","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":"Vanillin Mitigates the MPTP-Induced α-Synucleinopathy in a Mouse Model of Parkinson's Disease: Insights into the Involvement of Wnt/β-Catenin Signaling.","authors":"Linchi Rani, Amal Chandra Mondal","doi":"10.31083/j.jin2309175","DOIUrl":"10.31083/j.jin2309175","url":null,"abstract":"<p><strong>Background: </strong>The abnormal aggregation of α-synuclein (α-syn) in the substantia nigra pars compacta (SNpc) region of the brain is characteristic of Parkinson's disease (PD), leading to the selective demise of neurons. Modifications in the post-translational processing of α-syn, phosphorylation at Ser<sup>129</sup> in particular, are implicated in α-syn aggregation and are considered key hallmarks of PD. Furthermore, dysregulated Wnt/β-catenin signaling, influenced by glycogen synthase kinase-3 beta (GSK-3β), is implicated in PD pathogenesis. Inhibition of GSK-3β holds promise in promoting neuroprotection by enhancing the Wnt/β-catenin pathway.</p><p><strong>Methods: </strong>In our previous study utilizing 1-methyl-4-phenylpyridinium (MPP<sup>+</sup>)-administered differentiated SH-SY5Y cells and a PD mouse model, we explored Vanillin's neuroprotective properties and related mechanisms against neuronal loss induced by MPP<sup>+</sup>/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. In the current study, we elucidated the mitigating effects of Vanillin on motor impairments, P-Ser<sup>129</sup>-α-syn expression, Wnt/β-catenin signaling, and autophagic neuron death induced by MPTP in a mouse model of PD by performing motor function tests, western blot analysis and immunostaining.</p><p><strong>Results: </strong>Our results show that Vanillin effectively modulated the motor dysfunctions, GSK-3β expression, and activity, activated the Wnt/β-catenin signaling, and reduced autophagic neuronal demise in the MPTP-lesioned mice, highlighting its neuroprotective effects.</p><p><strong>Conclusions: </strong>These findings underscore the complex interplay between α-syn pathology, GSK-3β, Wnt/β-catenin signaling, and autophagic-cell death in PD pathogenesis. Targeting these pathways, particularly with Vanillin, can be a promising therapeutic strategy for restoring dopaminergic (DA-ergic) neuronal homeostasis and slowing the progression of PD. Further research is crucial to resolving existing disputes and translating these discoveries into effective therapeutic interventions for PD patients.</p>","PeriodicalId":16160,"journal":{"name":"Journal of integrative neuroscience","volume":"23 9","pages":"175"},"PeriodicalIF":2.5,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348291","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}