Neuroscience Insights最新文献

{"title":"The SMA Modifier Plastin 3 Targets Cell Membrane-Associated Proteins in Motoneurons.","authors":"Sibylle Jablonka, Natascha Schäfer","doi":"10.1177/26331055241226623","DOIUrl":"10.1177/26331055241226623","url":null,"abstract":"<p><p>Loss of the <i>Survival Motor Neuron (SMN)</i> gene inevitably leads to spinal muscular atrophy (SMA), one of the most common fatal neuromuscular diseases in children with FDA and EMA approved therapies. However, the cellular mechanisms leading to neuromuscular junction (NMJ) dysfunction due to impaired Ca²⁺ homeostasis in the presynaptic compartment remain largely unexplained. In the last decade, the so-called SMA modifiers have gained attention. The F-actin bundler Plastin 3 (PLS3) is one of them and counteracts neurotransmission defects, including altered vesicle endocytosis, in Smn-deficient NMJs. Properly bundled F-actin is the basis for the translocation and arrangement of transmembrane proteins at the cell surface. Our recently published data by Hennlein et al., J Cell Biol. (2023) clearly showed that Smn deficiency impairs the F-actin dependent translocation of the high-affinity BDNF receptor TrkB to the cell surface resulting in reduced BDNF-mediated TrkB activation in motor axon terminals. Strikingly, the overexpression of PLS3 restores TrkB availability, and significantly improves the clustering of the active zone-associated voltage-gated calcium channel Ca_v2.2 in growth cones of Smn-deficient motoneurons. These observations raise the question of how PLS3 mediates the proper cell surface localization and cluster-like formation of Ca_v2.2 in motor axon terminals.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10799582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139514113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dozing Off With Drosophila: The Effect of Disrupted Circadian Rhythms and Sleep Disturbance on Mortality, Mood, and Addiction.","authors":"Rania S Lateef, Bibhaw Pokharel, Tasnuva Nuhat Shafin","doi":"10.1177/26331055231218698","DOIUrl":"10.1177/26331055231218698","url":null,"abstract":"<p><p>Many environmental factors can disrupt sleep and circadian rhythms, yet the consequences of such disruptions are poorly understood. The main goals of this project were to study the effects of disrupted circadian rhythms and sleep disturbance on <i>Drosophila melanogaster's</i>: (1) lifespan, (2) depression-like behaviors, and (3) propensity to consume caffeine-containing media. Three experimental groups were used: controls, Circadian Dysfunction (CD), and Sleep Disturbance (SD). Circadian disruption (CD): used flies with <i>Tim</i>⁰¹ mutation, which eliminates circadian behavioral rhythms. Sleep disturbance (SD): used flies subjected to hourly light exposure and manual mechanical disruption, for 48 hours. To assess the effect on lifespan, the percent of flies surviving over time, within each group, was calculated. Impaired geotaxis, or loss of climbing motivation, was assessed as a measure of a depression-like state. Preference for caffeine-containing food was evaluated using a choice chamber where caffeine enriched, and regular media were presented to flies. Group differences were analyzed with survival curves. Chi-square tests were used for the categorical variables. Survival curve analysis showed that Flies with the <i>timeless</i> gene mutation (<i>tim</i>⁰¹) have a significantly shorter lifespan than controls. Geotaxis was not significantly impaired by sleep disturbance, but it was negatively affected by circadian dysfunction. Both the Circadian Dysfunction and Sleep Disturbance groups showed a preference for caffeine-containing food, after 72 hours of exposure to it, although the Circadian Dysfunction group was much more affected than the Sleep Disturbance group. Sleep and circadian disturbances can negatively influence physical and mental wellbeing and the accompanying molecular mechanisms, as well as disrupted brain physiology, must be studied. It is critical to identify and minimize social and environmental disruptors of such biological rhythms.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10749519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139037990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain.","authors":"Santosh Anand, Senthilkumar Rajagopal","doi":"10.1177/26331055231220340","DOIUrl":"10.1177/26331055231220340","url":null,"abstract":"<p><p>The transient receptor potential (TRP) superfamily of ion channels in humans comprises voltage-gated, non-selective cation channels expressed both in excitable as well as non-excitable cells. Four TRP channel subunits associate to create functional homo- or heterotetramers that allow the influx of calcium, sodium, and/or potassium. These channels are highly abundant in the brain and kidney and are important mediators of diverse biological functions including thermosensation, vascular tone, flow sensing in the kidney and irritant stimuli sensing. Inherited or acquired dysfunction of TRP channels influences cellular functions and signaling pathways resulting in multifaceted disorders affecting skeletal, renal, cardiovascular, and nervous systems. Studies have demonstrated the involvement of these channels in the generation and transduction of pain. Based on the multifaceted role orchestrated by these TRP channels, modulation of the activity of these channels presents an important strategy to influence cellular function by regulating intracellular calcium levels as well as membrane excitability. Therefore, there has been a remarkable pharmaceutical inclination toward TRP channels as therapeutic interventions. Several candidate drugs influencing the activity of these channels are already in the clinical trials pipeline. The present review encompasses the current understanding of TRP channels and TRP modulators in pain and pain management.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10749524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139038392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positive Association Between the Immunogenetic Human Leukocyte Antigen (HLA) Profiles of Multiple Sclerosis and Brain Cancer.","authors":"Lisa M James, Apostolos P Georgopoulos","doi":"10.1177/26331055231214543","DOIUrl":"10.1177/26331055231214543","url":null,"abstract":"<p><p>Previous research has documented elevated risk of brain cancer in patients with multiple sclerosis (MS). Separately, human leukocyte antigen (HLA) has been implicated in protection or susceptibility for both conditions. The aim of the current study was to assess a possible role of shared immunogenetic influence on risk of MS and brain cancer. We first identified an immunogenetic profile for each condition based on the covariance between the population frequency of 127 high-resolution HLA alleles and the population prevalence of each condition in 14 Continental Western European countries and then evaluated the correspondence between MS and brain cancer immunogenetic profiles. Also, since each individual carries 12 HLA alleles (2 × 6 genes), we estimated HLA protection and susceptibility for MS and brain cancer at the individual level. We found that the immunogenetic profiles of MS and brain cancer were highly correlated overall (<i>P</i> < .001) and across all 6 HLA genes with the strongest association observed for DRB1, followed by DQB1 and HLA-A. These findings of immunogenetic overlap between MS and brain cancer are discussed in light of the role of HLA in the immune system response to viruses and other foreign antigens.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138478784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling Resilience to Alzheimer's Disease: Insights From Brain Regional Proteomic Markers.","authors":"Zhi Huang, Gennifer E Merrihew, Eric B Larson, Jea Park, Deanna Plubell, Edward J Fox, Kathleen S Montine, C Dirk Keene, Caitlin S Latimer, James Y Zou, Michael J MacCoss, Thomas J Montine","doi":"10.1177/26331055231201600","DOIUrl":"10.1177/26331055231201600","url":null,"abstract":"<p><p>Studying proteomics data of the human brain could offer numerous insights into unraveling the signature of resilience to Alzheimer's disease. In our previous study with rigorous cohort selection criteria that excluded 4 common comorbidities, we harnessed multiple brain regions from 43 research participants with 12 of them displaying cognitive resilience to Alzheimer's disease. Based on the previous findings, this work focuses on 6 proteins out of the 33 differentially expressed proteins associated with resilience to Alzheimer's disease. These proteins are used to construct a decision tree classifier, enabling the differentiation of 3 groups: (i) healthy control, (ii) resilience to Alzheimer's disease, and (iii) Alzheimer's disease with dementia. Our analysis unveiled 2 important regional proteomic markers: Aβ peptides in the hippocampus and PA1B3 in the inferior parietal lobule. These findings underscore the potential of using distinct regional proteomic markers as signatures in characterizing the resilience to Alzheimer's disease.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ec/f2/10.1177_26331055231201600.PMC10557413.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41151300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Duvelisib, a Selective PI3K Inhibitor on Seizure Activity in Pentylenetetrazole-Induced Convulsions Animal Model.","authors":"Mahnaz Abdolrahmani,&nbsp;Naser Mirazi,&nbsp;Abdolkarim Hosseini","doi":"10.1177/26331055231198013","DOIUrl":"10.1177/26331055231198013","url":null,"abstract":"Epilepsy is one of the most common neurological diseases, which is caused by abnormal brain activity. A wide variety of studies have shown the importance of the phosphatidylinositol-3-kinase (PI3K) signaling pathway in epilepsy pathogenesis. Duvelisib (DUV) is a selective inhibitor of PI3K. The present study investigated the anticonvulsant potential of DUV in a rat model of pentylenetetrazole (PTZ)-induced convulsions. Male Wistar rats (200-250 g, 8 weeks old) were injected intraperitoneally (IP) with DUV at different doses of 5 and 10 mg/kg, or vehicle 30 minutes prior to PTZ (70 mg/kg, IP) treatment. Based on Racine’s scale, behavioral seizures were assessed. The results showed that pretreatment with DUV prolonged the seizure stages according to the Racine scale, significantly decreased the duration of general tonic-clonic seizure and reduced the number of myoclonic jerks (P < .05). In conclusion, we found that PI3K antagonist DUV significantly reduced PTZ-induced seizures, indicating that DUV exerts an anticonvulsant effect by inhibiting PI3K signaling pathway.","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e5/cb/10.1177_26331055231198013.PMC10503276.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10635656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relationship Between COVID-19 and the Development of Depression: Implications on Mental Health.","authors":"Padmashri A Shetty, Lena Ayari, Jessica Madry, Colton Betts, Diana M Robinson, Batool F Kirmani","doi":"10.1177/26331055231191513","DOIUrl":"10.1177/26331055231191513","url":null,"abstract":"<p><p>Initially, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease-2019 (COVID-19), was predominantly considered to primarily affect the respiratory system. However, later studies revealed that it also affects brain function through its ability to bind to the angiotensin-converting enzyme type 2 (ACE2) receptors expressed on neural cells. Our study involved a comprehensive review of literature aiming to investigate the relationship between COVID-19 and the development of depression. Our analysis shows a connection between these 2 conditions, as a consequence of the inflammatory response in the nervous system to the COVID-19 virus and the psychophysiological effects of the pandemic. In COVID-19 patients, depression can arise either due to the direct viral infection of the brain or as a result of an indirect immune response triggering neuroinflammation after a cytokine storm. The resulting depression can be treated with non-pharmacological therapies such as psychotherapy, antidepressant medications, or a combination of these treatments depending on the severity of the symptoms.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/72/bc/10.1177_26331055231191513.PMC10441207.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10048657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of SARS-CoV-2-induced Encephalopathy and Encephalitis in COVID-19 Cases.","authors":"Aaron Vengalil, Damir Nizamutdinov, Matthew Su, Jason H Huang","doi":"10.1177/26331055231172522","DOIUrl":"10.1177/26331055231172522","url":null,"abstract":"<p><p>The SARS-CoV-2 virus caused an unprecedented pandemic around the globe, infecting 36.5 million people and causing the death of over 1 million in the United States of America alone. COVID-19 patients demonstrated respiratory symptoms, cardiovascular complications, and neurologic symptoms, which in most severe cases included encephalopathy and encephalitis. Hypoxia and the uncontrolled proliferation of cytokines are commonly recognized to cause encephalopathy, while the retrograde trans-synaptic spread of the virus is thought to cause encephalitis in SARS-CoV-2-induced pathogenesis. Although recent research revealed some mechanisms explaining the development of neurologic symptoms, it still remains unclear whether interactions between these mechanisms exist. This review focuses on the discussion and analysis of previously reported hypotheses of SARS-CoV-2-induced encephalopathy and encephalitis and looks into possible overlaps between the pathogenesis of both neurological outcomes of the disease. Promising therapeutic approaches to prevent and treat SARS-CoV-2-induced neurological complications are also covered. More studies are needed to further investigate the dominant mechanism of pathogenesis for developing more effective preventative measures in COVID-19 cases with the neurologic presentation.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/90/af/10.1177_26331055231172522.PMC10225804.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9551401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Directed Functional Brain Connectivity is Altered in Sub-threshold Amyloid-β Accumulation in Cognitively Normal Individuals.","authors":"Mite Mijalkov, Dániel Veréb, Anna Canal-Garcia, Giovanni Volpe, Joana B Pereira","doi":"10.1177/26331055231161625","DOIUrl":"10.1177/26331055231161625","url":null,"abstract":"<p><p>Several studies have shown that amyloid-β (Aβ) deposition below the clinically relevant cut-off levels is associated with subtle changes in cognitive function and increases the risk of developing future Alzheimer's disease (AD). Although functional MRI is sensitive to early alterations occurring during AD, sub-threshold changes in Aβ levels have not been linked to functional connectivity measures. This study aimed to apply directed functional connectivity to identify early changes in network function in cognitively unimpaired participants who, at baseline, exhibit Aβ accumulation below the clinically relevant threshold. To this end, we analyzed baseline functional MRI data from 113 cognitively unimpaired participants of the Alzheimer's Disease Neuroimaging Initiative cohort who underwent at least one ¹⁸F-florbetapir-PET after the baseline scan. Using the longitudinal PET data, we classified these participants as Aβ negative (Aβ-) non-accumulators (n = 46) and Aβ- accumulators (n = 31). We also included 36 individuals who were amyloid-positive (Aβ+) at baseline and continued to accumulate Aβ (Aβ+ accumulators). For each participant, we calculated whole-brain directed functional connectivity networks using our own anti-symmetric correlation method and evaluated their global and nodal properties using measures of network segregation (clustering coefficient) and integration (global efficiency). When compared to Aβ- non-accumulators, the Aβ- accumulators showed lower global clustering coefficient. Moreover, the Aβ+ accumulator group exhibited reduced global efficiency and clustering coefficient, which at the nodal level mainly affected the superior frontal gyrus, anterior cingulate cortex, and caudate nucleus. In Aβ- accumulators, global measures were associated with lower baseline regional PET uptake values, as well as higher scores on the Modified Preclinical Alzheimer Cognitive Composite. Our findings indicate that directed connectivity network properties are sensitive to subtle changes occurring in individuals who have not yet reached the threshold for Aβ positivity, which makes them a potentially viable marker to detect negative downstream effects of very early Aβ pathology.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2023-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10064157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9240377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Citicoline in Patients With Mild Cognitive Impairment.","authors":"Pedro E Bermejo, Rodolfo Dorado, María Ascensión Zea-Sevilla","doi":"10.1177/26331055231152496","DOIUrl":"10.1177/26331055231152496","url":null,"abstract":"<p><p>The term mild cognitive impairment (MCI) defines an intermediate state between normal aging and dementia. Vascular cognitive impairment refers to a decline in cognitive function that is caused by or associated with vascular disease and comprises all the spectrum of cognitive impairments, from MCI of vascular origin to vascular dementia. One of the available treatments for cognitive impairment is cytidine diphosphate-choline (CDP-Choline), or citicoline. The objective of the present manuscript is to provide complete evidence about the efficacy of citicoline for MCI, especially of vascular origin, but also due to other neurodegenerative disorders. Citicoline is a pharmaceutical product constituted by the combination of 2 natural molecules (cytidine and choline) and is marketed as a food supplement. It has been proposed to provide neuroprotective effects through diverse mechanisms of action. Taking into account the available literature, citicoline has shown a consistent improvement in cognitive function in patients with MCI, especially of vascular origin. Moreover, it provides beneficial effects on vascular, Alzheimer, and mixed dementias, stroke sequelae, intracerebral hemorrhages, traumatic brain injuries, and neurodegenerative diseases. Long-term treatment with citicoline has also been demonstrated to be well-tolerated and has not been associated with severe adverse events. Citicoline is a safe, well-tolerated, and promising agent with evidenced neuroprotective properties.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e4/a6/10.1177_26331055231152496.PMC9936398.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10763421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}