Neuroscience Insights最新文献

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Brain Networks of Connectionally Unique Basolateral Amygdala Cell Types 连接独特的基底外侧杏仁核细胞类型的脑网络
IF 3.6
Neuroscience Insights Pub Date : 2022-01-01 DOI: 10.1177/26331055221080175
Houri Hintiryan, Hong-wei Dong
{"title":"Brain Networks of Connectionally Unique Basolateral Amygdala Cell Types","authors":"Houri Hintiryan, Hong-wei Dong","doi":"10.1177/26331055221080175","DOIUrl":"https://doi.org/10.1177/26331055221080175","url":null,"abstract":"Different brain regions structurally interconnected through networks regulate behavior output. Therefore, understanding the functional organization of the brain in health and disease necessitates a foundational anatomic roadmap to its network organization. To provide this to the research community, our lab has systematically traced thousands of pathways in the mouse brain and has applied computational measures to determine the network architecture of major brain systems. Toward this effort, the brain-wide networks of the basolateral amygdalar complex (BLA) were recently generated. The data revealed uniquely connected cell types within the same BLA nucleus that were constituents of distinct neural networks. Here, we elaborate on how these connectionally unique BLA cell types fit within the larger cortico-basal ganglia and limbic networks that were previously described by our team. The significance and utility of high quality, detailed anatomic data is also discussed.","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49646070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 2
Protein Network Analysis Reveals a Functional Connectivity of Dysregulated Processes in ALS and SMA 蛋白质网络分析揭示了ALS和SMA失调过程的功能连通性
IF 3.6
Neuroscience Insights Pub Date : 2022-01-01 DOI: 10.1177/26331055221087740
S. Kubinski, P. Claus
{"title":"Protein Network Analysis Reveals a Functional Connectivity of Dysregulated Processes in ALS and SMA","authors":"S. Kubinski, P. Claus","doi":"10.1177/26331055221087740","DOIUrl":"https://doi.org/10.1177/26331055221087740","url":null,"abstract":"Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases which are characterized by the loss of motoneurons within the central nervous system. SMA is a monogenic disease caused by reduced levels of the Survival of motoneuron protein, whereas ALS is a multi-genic disease with over 50 identified disease-causing genes and involvement of environmental risk factors. Although these diseases have different causes, they partially share identical phenotypes and pathomechanisms. To analyze and identify functional connections and to get a global overview of altered pathways in both diseases, protein network analyses are commonly used. Here, we used an in silico tool to test for functional associations between proteins that are involved in actin cytoskeleton dynamics, fatty acid metabolism, skeletal muscle metabolism, stress granule dynamics as well as SMA or ALS risk factors, respectively. In network biology, interactions are represented by edges which connect proteins (nodes). Our approach showed that only a few edges are necessary to present a complex protein network of different biological processes. Moreover, Superoxide dismutase 1, which is mutated in ALS, and the actin-binding protein profilin1 play a central role in the connectivity of the aforementioned pathways. Our network indicates functional links between altered processes that are described in either ALS or SMA. These links may not have been considered in the past but represent putative targets to restore altered processes and reveal overlapping pathomechanisms in both diseases.","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46276512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Commentary: How Do Microglia Regulate Neural Circuit Connectivity and Activity in the Adult Brain? 评论:小胶质细胞如何调节成人大脑中的神经回路连接和活动?
IF 3.6
Neuroscience Insights Pub Date : 2022-01-01 DOI: 10.1177/26331055211071124
Yong-Jun Liu, Kim N Green, Todd C Holmes, Xiangmin Xu
{"title":"Commentary: How Do Microglia Regulate Neural Circuit Connectivity and Activity in the Adult Brain?","authors":"Yong-Jun Liu,&nbsp;Kim N Green,&nbsp;Todd C Holmes,&nbsp;Xiangmin Xu","doi":"10.1177/26331055211071124","DOIUrl":"https://doi.org/10.1177/26331055211071124","url":null,"abstract":"<p><p>Microglia are the primary immune cells in CNS. Recent work shows that microglia are also essential for proper brain development through synaptic pruning and remodeling during early life development. But the question of whether and how microglia regulate synaptic connectivity in the adult brain remains open. Our recently published study provides new insights into the functional roles of microglia in the adult mouse brain. We find that chronic depletion of microglia via CSF1R inhibitors in the visual cortex in adult mice induces a dramatic increase in perineuronal nets, and enhances neural activities of both excitatory neurons and parvalbumin interneurons. These findings highlight new potential therapeutic avenues to enhance adult neural plasticity by manipulating microglia.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"17 ","pages":"26331055211071124"},"PeriodicalIF":3.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/bc/10.1177_26331055211071124.PMC8796061.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10327168","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}
引用次数: 1
Test-Retest Reliability and Agreement of Single Pulse Transcranial Magnetic Stimulation (TMS) for Measuring Activity in Motor Cortex in Patients With Acute Ischemic Stroke. 单脉冲经颅磁刺激(TMS)测量急性缺血性脑卒中患者运动皮质活动的重测信度和一致性。
IF 3.6
Neuroscience Insights Pub Date : 2022-01-01 DOI: 10.1177/26331055221145002
Busk Henriette, Nilsen Marianne, Pedersen Julie Rønne, Kristensen Malene Glavin, Kjær Troels Wesenberg, Skou Søren Thorgaard, Wienecke Troels
{"title":"Test-Retest Reliability and Agreement of Single Pulse Transcranial Magnetic Stimulation (TMS) for Measuring Activity in Motor Cortex in Patients With Acute Ischemic Stroke.","authors":"Busk Henriette,&nbsp;Nilsen Marianne,&nbsp;Pedersen Julie Rønne,&nbsp;Kristensen Malene Glavin,&nbsp;Kjær Troels Wesenberg,&nbsp;Skou Søren Thorgaard,&nbsp;Wienecke Troels","doi":"10.1177/26331055221145002","DOIUrl":"https://doi.org/10.1177/26331055221145002","url":null,"abstract":"<p><strong>Background: </strong>Transcranial magnetic stimulation (TMS) is often used to examine neurophysiology. We aimed to investigate the inter-rater reliability and agreement of single pulse TMS in hospitalised acute ischemic stroke patients.</p><p><strong>Methods: </strong>Thirty-one patients with first-time acute ischemic stroke (median age 72 (IQR 64-75), 35% females) underwent TMS motor threshold (MT) assessment in 4 muscles bilaterally, conducted by 1 of 2 physiotherapists. Test-retest reliability was evaluated using a two-way random effects model (2,1) absolute agreement-type Interclass Correlation Coefficient (ICC). Standard Error of Measurement (SEM) and Smallest Detectable Change (SDC) were used to evaluate agreement.</p><p><strong>Results: </strong>Reliability, SEM, and SDC of TMS was found to be moderate in right opponens pollicis (0.78 [CI 95% 0.55-0.89], SEM: 4.51, SDC: 12.51), good in right vastus medialis and tibial anterior (0.88 [CI 95% 0.72-0.96], SEM: 2.89, SDC: 8.01 and 0.88 [CI 95% 0.76-0.94], SEM: 2.88, SDC: 7.98 respectively), and excellent in right and left biceps brachii (0.98 [CI 95% 0.96-0.99], SEM: 1.79 SDC: 4.96, and 0.94 [CI 95% 0.89-0.97], SEM: 2.17 SDC: 6.01), opponens pollicis (0.92 [CI 95% 0.83-0.96], SEM: 2.68 SDC: 8.26, vastus medialis (0.92 [CI 95% 0.84-0.96], SEM: 2.87 SDC: 7.95), and tibial anterior (0.93 [CI 95% 0.86-0.96], SEM: 2.51 SDC: 6.95).</p><p><strong>Conclusion: </strong>The TMS demonstrated moderate to excellent inter-rater reliability confirming the ability of these measures to reliably discriminate between individuals in the current study sample. Improvements of less than 4.96 to 12.51 could be a result of measurement error and may therefore not be considered a true change.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"17 ","pages":"26331055221145002"},"PeriodicalIF":3.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/78/b0/10.1177_26331055221145002.PMC9791285.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9260458","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}
引用次数: 1
A Tailored Music-Motor Therapy and Real-Time Biofeedback Mobile Phone App (‘GotRhythm’) to Promote Rehabilitation Following Stroke: A Pilot Study 定制的音乐-运动疗法和实时生物反馈手机应用程序(“gorhythm”)促进中风后康复:一项试点研究
IF 3.6
Neuroscience Insights Pub Date : 2022-01-01 DOI: 10.1177/26331055221100587
Katherine Hankinson, A. Shaykevich, A. Vallence, J. Rodger, Michael A. Rosenberg, C. Etherton-Beer
{"title":"A Tailored Music-Motor Therapy and Real-Time Biofeedback Mobile Phone App (‘GotRhythm’) to Promote Rehabilitation Following Stroke: A Pilot Study","authors":"Katherine Hankinson, A. Shaykevich, A. Vallence, J. Rodger, Michael A. Rosenberg, C. Etherton-Beer","doi":"10.1177/26331055221100587","DOIUrl":"https://doi.org/10.1177/26331055221100587","url":null,"abstract":"Background: Stroke persists as an important cause of long-term disability world-wide with the need for rehabilitation strategies to facilitate plasticity and improve motor function in stroke survivors. Rhythm-based interventions can improve motor function in clinical populations. This study tested a novel music-motor software application ‘GotRhythm’ on motor function after stroke. Methods: Participants were 22 stroke survivors undergoing inpatient rehabilitation in a subacute stroke ward. Participants were randomised to the GotRhythm intervention (combining individualised music and augmented auditory feedback along with wearable sensors to deliver a personalised rhythmic auditory stimulation training protocol) or usual care. Intervention group participants were offered 6-weeks of the GotRhythm intervention, consisting of a supervised 20-minute music-motor therapy session using GotRhythm conducted 3 times a week for 6 weeks. The primary feasibility outcomes were adherence to the intervention and physical function (change in the Fugl-Meyer Assessment of Motor Recovery score) measured at baseline, after 3-weeks and at end of the intervention period (6-weeks). Results: Three of 10 participants randomised to the intervention did not receive any of the GotRhythym music-motor therapy. Of the remaining 7 intervention group participants, only 5 completed the 3-week mid-intervention assessment and only 2 completed the 6-week post-intervention assessment. Participants who used the intervention completed 5 (IQR 4,7) sessions with total ‘dose’ of the intervention of 70 (40, 201) minutes. Conclusion: Overall, adherence to the intervention was poor, highlighting that application of technology assisted music-based interventions for stroke survivors in clinical environments is challenging along with usual care, recovery, and the additional clinical load.","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"17 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44197673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 7
Thanks to Reviewers 感谢审稿人
IF 3.6
Neuroscience Insights Pub Date : 2021-01-01 DOI: 10.1177/26331055211000487
{"title":"Thanks to Reviewers","authors":"","doi":"10.1177/26331055211000487","DOIUrl":"https://doi.org/10.1177/26331055211000487","url":null,"abstract":"","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"16 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26331055211000487","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43629984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hearing Impaired Participants Improve More Under Envelope-Transcranial Alternating Current Stimulation When Signal to Noise Ratio Is High. 当信噪比高时,经颅交流电刺激对听力受损者的改善效果更好。
IF 3.6
Neuroscience Insights Pub Date : 2021-01-01 DOI: 10.1177/2633105520988854
Jules Erkens, Michael Schulte, Matthias Vormann, Anna Wilsch, Christoph S Herrmann
{"title":"Hearing Impaired Participants Improve More Under Envelope-Transcranial Alternating Current Stimulation When Signal to Noise Ratio Is High.","authors":"Jules Erkens,&nbsp;Michael Schulte,&nbsp;Matthias Vormann,&nbsp;Anna Wilsch,&nbsp;Christoph S Herrmann","doi":"10.1177/2633105520988854","DOIUrl":"https://doi.org/10.1177/2633105520988854","url":null,"abstract":"<p><p>An issue commonly expressed by hearing aid users is a difficulty to understand speech in complex hearing scenarios, that is, when speech is presented together with background noise or in situations with multiple speakers. Conventional hearing aids are already designed with these issues in mind, using beamforming to only enhance sound from a specific direction, but these are limited in solving these issues as they can only modulate incoming sound at the cochlear level. However, evidence exists that age-related hearing loss might partially be caused later in the hearing processes due to brain processes slowing down and becoming less efficient. In this study, we tested whether it would be possible to improve the hearing process at the cortical level by improving neural tracking of speech. The speech envelopes of target sentences were transformed into an electrical signal and stimulated onto elderly participants' cortices using transcranial alternating current stimulation (tACS). We compared 2 different signal to noise ratios (SNRs) with 5 different delays between sound presentation and stimulation ranging from 50 ms to 150 ms, and the differences in effects between elderly normal hearing and elderly hearing impaired participants. When the task was performed at a high SNR, hearing impaired participants appeared to gain more from envelope-tACS compared to when the task was performed at a lower SNR. This was not the case for normal hearing participants. Furthermore, a post-hoc analysis of the different time-lags suggest that elderly were significantly better at a stimulation time-lag of 150 ms when the task was presented at a high SNR. In this paper, we outline why these effects are worth exploring further, and what they tell us about the optimal tACS time-lag.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"16 ","pages":"2633105520988854"},"PeriodicalIF":3.6,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2633105520988854","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10293194","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}
引用次数: 1
Effects of Tacrolimus and Other Immune Targeting Compounds on Binge-Like Ethanol Drinking in High Drinking in the Dark Mice. 他克莫司和其他免疫靶向化合物对深色小鼠高饮水中Binge样乙醇饮酒的影响。
IF 2.9
Neuroscience Insights Pub Date : 2020-11-25 eCollection Date: 2020-01-01 DOI: 10.1177/2633105520975412
Kolter B Grigsby, Antonia M Savarese, Pamela Metten, Barbara J Mason, Yuri A Blednov, John C Crabbe, Angela R Ozburn
{"title":"Effects of Tacrolimus and Other Immune Targeting Compounds on Binge-Like Ethanol Drinking in High Drinking in the Dark Mice.","authors":"Kolter B Grigsby, Antonia M Savarese, Pamela Metten, Barbara J Mason, Yuri A Blednov, John C Crabbe, Angela R Ozburn","doi":"10.1177/2633105520975412","DOIUrl":"10.1177/2633105520975412","url":null,"abstract":"<p><p>High Drinking in the Dark (HDID-1) mice represent a unique genetic risk model of binge-like drinking and a novel means of screening potential pharmacotherapies to treat alcohol use disorders (AUDs). We tested the effects of tacrolimus (0, 0.5, 1, and 2 mg/kg), sirolimus (0, 5, 10, and 20 mg/kg), palmitoylethanolamide (PEA; 0, 75, 150, and 225 mg/kg), and secukinumab (0, 5, 20, and 60 mg/kg) on binge-like ethanol intake (2-day, \"Drinking in the Dark\" [DID]) and blood alcohol levels (BALs) in HDID-1 mice. Tacrolimus reduced ethanol intake and BALs. Tacrolimus had no effect on water intake, but reduced saccharin intake. There was no effect of sirolimus, PEA, or secukinumab on ethanol intake or BALs. These results compare and contrast with previous work addressing these compounds or their targeted mechanisms of action on ethanol drinking, highlighting the importance of screening a wide range of models and genotypes to inform the role of neuroimmune signaling in AUDs.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"15 ","pages":"2633105520975412"},"PeriodicalIF":2.9,"publicationDate":"2020-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ea/83/10.1177_2633105520975412.PMC7705291.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9970353","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}
引用次数: 0
The Effects of Early-Life Iron Deficiency on Brain Energy Metabolism. 生命早期缺铁对大脑能量代谢的影响。
IF 3.6
Neuroscience Insights Pub Date : 2020-01-01 DOI: 10.1177/2633105520935104
Thomas W Bastian, Raghavendra Rao, Phu V Tran, Michael K Georgieff
{"title":"The Effects of Early-Life Iron Deficiency on Brain Energy Metabolism.","authors":"Thomas W Bastian,&nbsp;Raghavendra Rao,&nbsp;Phu V Tran,&nbsp;Michael K Georgieff","doi":"10.1177/2633105520935104","DOIUrl":"https://doi.org/10.1177/2633105520935104","url":null,"abstract":"<p><p>Iron deficiency (ID) is one of the most prevalent nutritional deficiencies in the world. Iron deficiency in the late fetal and newborn period causes abnormal cognitive performance and emotional regulation, which can persist into adulthood despite iron repletion. Potential mechanisms contributing to these impairments include deficits in brain energy metabolism, neurotransmission, and myelination. Here, we comprehensively review the existing data that demonstrate diminished brain energetic capacity as a mechanistic driver of impaired neurobehavioral development due to early-life (fetal-neonatal) ID. We further discuss a novel hypothesis that permanent metabolic reprogramming, which occurs during the period of ID, leads to chronically impaired neuronal energetics and mitochondrial capacity in adulthood, thus limiting adult neuroplasticity and neurobehavioral function. We conclude that early-life ID impairs energy metabolism in a brain region- and age-dependent manner, with particularly strong evidence for hippocampal neurons. Additional studies, focusing on other brain regions and cell types, are needed.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"15 ","pages":"2633105520935104"},"PeriodicalIF":3.6,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2633105520935104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9699921","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}
引用次数: 38
Gene Transfer in Rodent Nervous Tissue Following Hindlimb Intramuscular Delivery of Recombinant Adeno-Associated Virus Serotypes AAV2/6, AAV2/8, and AAV2/9. 重组腺相关病毒血清型AAV2/6、AAV2/8和AAV2/9在鼠后肢肌内传递后神经组织的基因转移
IF 3.6
Neuroscience Insights Pub Date : 2019-12-31 eCollection Date: 2019-01-01 DOI: 10.1177/1179069519889022
Asad Jan, Mette Richner, Christian B Vægter, Jens R Nyengaard, Poul H Jensen
{"title":"Gene Transfer in Rodent Nervous Tissue Following Hindlimb Intramuscular Delivery of Recombinant Adeno-Associated Virus Serotypes AAV2/6, AAV2/8, and AAV2/9.","authors":"Asad Jan,&nbsp;Mette Richner,&nbsp;Christian B Vægter,&nbsp;Jens R Nyengaard,&nbsp;Poul H Jensen","doi":"10.1177/1179069519889022","DOIUrl":"https://doi.org/10.1177/1179069519889022","url":null,"abstract":"<p><p>Recombinant adeno-associated virus (rAAV) vectors have emerged as the safe vehicles of choice for long-term gene transfer in mammalian nervous system. Recombinant adeno-associated virus-mediated localized gene transfer in adult nervous system following direct inoculation, that is, intracerebral or intrathecal, is well documented. However, recombinant adeno-associated virus delivery in defined neuronal populations in adult animals using less-invasive methods as well as avoiding ectopic gene expression following systemic inoculation remain challenging. Harnessing the capability of some recombinant adeno-associated virus serotypes for retrograde transduction may potentially address such limitations (Note: The term <i>retrograde transduction</i> in this manuscript refers to the uptake of injected recombinant adeno-associated virus particles at nerve terminals, retrograde transport, and subsequent transduction of nerve cell soma). In some studies, recombinant adeno-associated virus serotypes 2/6, 2/8, and 2/9 have been shown to exhibit transduction of connected neuroanatomical tracts in adult animals following lower limb intramuscular recombinant adeno-associated virus delivery in a pattern suggestive of retrograde transduction. However, an extensive side-by-side comparison of these serotypes following intramuscular delivery regarding tissue viral load, and the effect of promoter on transgene expression, has not been performed. Hence, we delivered recombinant adeno-associated virus serotypes 2/6, 2/8, or 2/9 encoding enhanced green fluorescent protein (eGFP), under the control of either cytomegalovirus (CMV) or human synapsin (hSyn) promoter, via a single unilateral hindlimb intramuscular injection in the bicep femoris of adult C57BL/6J mice. Four weeks post injection, we quantified viral load and transgene (enhanced green fluorescent protein) expression in muscle and related nervous tissues. Our data show that the select recombinant adeno-associated virus serotypes transduce sciatic nerve and groups of neurons in the dorsal root ganglia on the injected side, indicating that the intramuscular recombinant adeno-associated virus delivery is useful for achieving gene transfer in local neuroanatomical tracts. We also observed sparse recombinant adeno-associated virus viral delivery or eGFP transduction in lumbar spinal cord and a noticeable lack thereof in brain. Therefore, further improvements in recombinant adeno-associated virus design are warranted to achieve efficient widespread retrograde transduction following intramuscular and possibly other peripheral routes of delivery.</p>","PeriodicalId":36527,"journal":{"name":"Neuroscience Insights","volume":"14 ","pages":"1179069519889022"},"PeriodicalIF":3.6,"publicationDate":"2019-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1179069519889022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37895922","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}
引用次数: 6
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