Brain and neuroscience advances最新文献

{"title":"The International BNA 2023 Festival of Neuroscience","authors":"","doi":"10.1177/23982128231180246","DOIUrl":"https://doi.org/10.1177/23982128231180246","url":null,"abstract":"","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49022280","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}

{"title":"Teriflunomide treatment outcomes in multiple sclerosis: A Portuguese real-life experience.","authors":"Carla Cecília Nunes,&nbsp;Pedro Abreu,&nbsp;Filipe Correia,&nbsp;Irene Mendes,&nbsp;Ana Martins da Silva","doi":"10.1177/23982128231185290","DOIUrl":"https://doi.org/10.1177/23982128231185290","url":null,"abstract":"<p><p>Teriflunomide is an oral disease-modifying therapy for relapsing-remitting multiple sclerosis patients. A decline in physical and cognitive functions, which negatively impacts their quality of life (QoL), is observed in relapsing-remitting multiple sclerosis patients. The aim of this study was to characterise adult Portuguese relapsing-remitting multiple sclerosis patients treated with teriflunomide in routine clinical practice concerning their quality of life, comorbidities, treatment effectiveness, satisfaction, compliance and safety. TeriLIVE-QoL was a multicentre, non-interventional, prospective cohort study that collected demographic and clinical characteristics, patient-reported outcomes and adverse events from patients treated with teriflunomide of 14 mg over 2 years. Notably, around 18 months of this period occurred during the COVID-19 pandemic. Of the 99 participants, 25% were treatment-naïve. Annualised relapse rate and the score for the Hospital Anxiety and Depression Scale decreased after 1 (p = 0.01) and 2 years of treatment (p < 0.001), respectively. Convenience (p = 0.001), effectiveness (p = 0.002) and global satisfaction scores (p < 0.001) presented high values (up to 95.6) and continued to improve along the study. Treatment persistence was 77%, and compliance reached 82% 2 years after initiation. Three patients experienced serious adverse events. TeriLIVE-QoL provides real-world evidence of clinical effectiveness, high treatment satisfaction, consistent safety and improved psychiatric outcomes, associated with elevated treatment persistence and compliance in patients treated with teriflunomide.iance reached 82% 2 years after initiation. Three patients experienced serious adverse events.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"7 ","pages":"23982128231185290"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10363901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9872740","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":"Brain and Neuroscience Advances 2023.","authors":"Kate Baker","doi":"10.1177/23982128231167484","DOIUrl":"https://doi.org/10.1177/23982128231167484","url":null,"abstract":"","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"7 ","pages":"23982128231167484"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10070748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9277367","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":"Celebrating the life and research of BNA Past-President Colin Blakemore.","authors":"Rana Fetit","doi":"10.1177/23982128231195514","DOIUrl":"https://doi.org/10.1177/23982128231195514","url":null,"abstract":"<p><p>Professor Sir Colin Blakemore was a remarkable neuroscientist, persuasive communicator, and brave advocate for animal research who, sadly, passed away in June 2022 from amyotrophic lateral sclerosis. His work helped establish the concept of neuronal plasticity, which was fundamental to our understanding of the postnatal brain and continues to impact our outlook on neurodegenerative disorders. The BNA2023 Festival of Neuroscience dedicated its last plenary session in his honour, bringing together five prominent neuroscientists whose careers were shaped by Professor Blakemore. Here, we summarise the speakers' reflections on how Colin's support, generosity, and foresight influenced their academic paths, inspired their research, and changed their outlook on life.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"7 ","pages":"23982128231195514"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/30/b1/10.1177_23982128231195514.PMC10460290.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10112224","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":"Apolipoprotein E isoform does not influence trans-synaptic spread of tau pathology in a mouse model.","authors":"Caitlin Davies,&nbsp;Jane Tulloch,&nbsp;Ellie Yip,&nbsp;Lydia Currie,&nbsp;Marti Colom-Cadena,&nbsp;Susanne Wegmann,&nbsp;Bradley T Hyman,&nbsp;Lewis Wilkins,&nbsp;Monique Hooley,&nbsp;Makis Tzioras,&nbsp;Tara L Spires-Jones","doi":"10.1177/23982128231191046","DOIUrl":"https://doi.org/10.1177/23982128231191046","url":null,"abstract":"<p><p>A key hallmark of Alzheimer's disease (AD) is the accumulation of hyperphosphorylated tau in neurofibrillary tangles. This occurs alongside neuroinflammation and neurodegeneration. Pathological tau propagates through the AD brain in a defined manner, which correlates with neuron and synapse loss and cognitive decline. One proposed mechanism of tau spread is through synaptically connected brain structures. Apolipoprotein E4 (<i>APOE4</i>) genotype is the strongest genetic risk factor for late-onset AD and is associated with increased tau burden. Whether the apolipoprotein E (<i>APOE</i>) genotype influences neurodegeneration via tau spread is currently unknown. Here, we demonstrate that virally expressed human tau (with the P301L mutation) injected into mouse entorhinal cortex at 5-6 months or 15-16 months of age spreads trans-synaptically to the hippocampus by 14 weeks post-injection. Injections of tau in mice expressing human <i>APOE2</i>, <i>APOE3</i> or <i>APOE4</i>, as well as <i>APOE</i> knock-outs, showed that tau can spread trans-synaptically in all genotypes and that <i>APOE</i> genotype and age do not affect the spread of tau. These data suggest that <i>APOE</i> genotype is not directly linked to synaptic spread of tau in our model, but other mechanisms involving non-cell autonomous manners of tau spread are still possible.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"7 ","pages":"23982128231191046"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10433884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10105522","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":"Septotemporal variation in modulation of synaptic transmission, paired-pulse ratio and frequency facilitation/depression by adenosine and GABA_B receptors in the rat hippocampus.","authors":"Maria A Samara,&nbsp;George D Oikonomou,&nbsp;George Trompoukis,&nbsp;Georgia Madarou,&nbsp;Maria Adamopoulou,&nbsp;Costas Papatheodoropoulos","doi":"10.1177/23982128221106315","DOIUrl":"https://doi.org/10.1177/23982128221106315","url":null,"abstract":"<p><p>Short-term synaptic plasticity represents a fundamental mechanism in neural information processing and is regulated by neuromodulators. Here, using field recordings from the CA1 region of adult rat hippocampal slices, we show that excitatory synaptic transmission is suppressed by strong but not moderate activation of adenosine A₁ receptors by 2-Chloro-N⁶-cyclopentyladenosine (CCPA) more in the dorsal than the ventral hippocampus; in contrast, both mild and strong activation of GABA_B receptors by baclofen (1 μM, 10 μM) suppress synaptic transmission more in the ventral than the dorsal hippocampus. Using a 10-pulse stimulation train of variable frequency, we found that CCPA modulates short-term synaptic plasticity independently of the suppression of synaptic transmission in both segments of the hippocampus and at stimulation frequencies greater than 10 Hz. However, specifically regarding the paired-pulse ratio (PPR) and frequency facilitation/depression (FF/D) we found significant drug action before but not after adjusting conditioning responses to control levels. Activation of GABA_BRs by baclofen suppressed synaptic transmission more in the ventral than the dorsal hippocampus. Furthermore, relatively high (10 μM) but not low (1 μM) baclofen concentration enhanced both PPR and FF in both hippocampal segments at stimulation frequencies greater than 1 Hz, independently of the suppression of synaptic transmission by baclofen. These results show that A₁Rs and GABA_BRs control synaptic transmission more effectively in the dorsal and the ventral hippocampus, respectively, and suggest that these receptors modulate PPR and FF/D at different frequency bands of afferent input, in both segments of the hippocampus.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":" ","pages":"23982128221106315"},"PeriodicalIF":0.0,"publicationDate":"2022-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bd/94/10.1177_23982128221106315.PMC9240614.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40467339","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":"Dissociating reward sensitivity and negative urgency effects on impulsivity in the five-choice serial reaction time task.","authors":"Chiara Toschi, Mona El-Sayed Hervig, Thiago Burghi, Torben Sell, Matthew Dominic Lycas, Parisa Moazen, Li Huang, Ulrik Gether, Trevor W Robbins, Jeffrey W Dalley","doi":"10.1177/23982128221102256","DOIUrl":"10.1177/23982128221102256","url":null,"abstract":"<p><p>Negative urgency describes the tendency for rash and impulsive behaviour during negative emotional states and has been linked to a number of psychiatric disorders. However, there has been limited research on negative urgency as an explanatory mechanism for impulsivity in experimental animals. Such research has important implications for elucidating the neurobiology of negative urgency and thereby the development of future therapeutic interventions. In this study, we investigated the effects of negative urgency using a partial reinforcement schedule to increase the frequency of non-rewarded (i.e. frustrative) trials in the five-choice serial reaction time task, a widely used task to assess visual attention and impulsivity. Using a Markov chain model to analyse trial-by-trial outcomes we found that premature (i.e. impulsive) responses in the five-choice serial reaction time task were more likely to occur after a non-rewarded trial, and mostly after a previous premature trial. However, contrary to the frustration hypothesis of negative urgency, increasing the probability of reinforcement (<i>p</i>(R)) from <i>p</i>(R) = 0.5 to <i>p</i>(R) = 1 increased the number of premature responses in each session. Micro and macro levels of analyses revealed that impulsivity in the five-choice serial reaction time task is governed by at least two processes, one dependent on the overall level of reinforcement hypothesised to determine the state of behavioural activation, the second dependent on trial-by-trial outcomes consistent with negative urgency effects. These processes may depend on distinct neurobiological mechanisms and have relevance for neuropsychiatric disorders that implicate impulsive behaviours dependent on positive and negative affective states.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":" ","pages":"23982128221102256"},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40042037","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":"Reducing voltage-dependent potassium channel Kv3.4 levels ameliorates synapse loss in a mouse model of Alzheimer's disease.","authors":"Jie Yeap, Chaitra Sathyaprakash, Jamie Toombs, Jane Tulloch, Cristina Scutariu, Jamie Rose, Karen Burr, Caitlin Davies, Marti Colom-Cadena, Siddharthan Chandran, Charles H Large, Matthew J M Rowan, Martin J Gunthorpe, Tara L Spires-Jones","doi":"10.1177/23982128221086464","DOIUrl":"10.1177/23982128221086464","url":null,"abstract":"<p><p>Synapse loss is associated with cognitive decline in Alzheimer's disease, and owing to their plastic nature, synapses are an ideal target for therapeutic intervention. Oligomeric amyloid beta around amyloid plaques is known to contribute to synapse loss in mouse models and is associated with synapse loss in human Alzheimer's disease brain tissue, but the mechanisms leading from Aβ to synapse loss remain unclear. Recent data suggest that the fast-activating and -inactivating voltage-gated potassium channel subtype 3.4 (Kv3.4) may play a role in Aβ-mediated neurotoxicity. Here, we tested whether this channel could also be involved in Aβ synaptotoxicity. Using adeno-associated virus and clustered regularly interspaced short palindromic repeats technology, we reduced Kv3.4 expression in neurons of the somatosensory cortex of APP/PS1 mice. These mice express human familial Alzheimer's disease-associated mutations in amyloid precursor protein and presenilin-1 and develop amyloid plaques and plaque-associated synapse loss similar to that observed in Alzheimer's disease brain. We observe that reducing Kv3.4 levels ameliorates dendritic spine loss and changes spine morphology compared to control virus. In support of translational relevance, Kv3.4 protein was observed in human Alzheimer's disease and control brain and is associated with synapses in human induced pluripotent stem cell-derived cortical neurons. We also noted morphological changes in induced pluripotent stem cell neurones challenged with human Alzheimer's disease-derived brain homogenate containing Aβ but, in this in vitro model, total mRNA levels of Kv3.4 were found to be reduced, perhaps as an early compensatory mechanism for Aβ-induced damage. Overall, our results suggest that approaches to reduce Kv3.4 expression and/or function in the Alzheimer's disease brain could be protective against Aβ-induced synaptic alterations.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"6 ","pages":"23982128221086464"},"PeriodicalIF":0.0,"publicationDate":"2022-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9415452","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 systematic review of studies investigating the acute effects of <i>N</i>-methyl-<i>D</i>-aspartate receptor antagonists on behavioural despair in normal animals suggests poor predictive validity.","authors":"Martin Viktorov, Matthew P Wilkinson, Victoria C E Elston, Medi Stone, Emma S J Robinson","doi":"10.1177/23982128221081645","DOIUrl":"10.1177/23982128221081645","url":null,"abstract":"<p><p>The ability of the <i>N</i>-methyl-<i>D</i>-aspartate receptor antagonist ketamine to induce a rapid and sustained antidepressant effect has led to a surge in pre-clinical studies investigating underlying mechanisms and seeking novel treatments. Animal models are key to this research as they can provide a behavioural readout linking underlying mechanisms to clinical benefits. However, quantifying depression-related behaviours in rodents represents a major challenge with the validity of traditional methods such as models of behavioural despair (forced swim test and tail suspension test) a topic of debate. While there is good evidence to support the value of using these behavioural readouts to study the effects of stress, these approaches have largely failed to detect reliable phenotypic effects in other disease models. In this systematic review, we identified publications which had tested <i>N</i>-methyl-<i>D</i>-aspartate receptor antagonists in normal animals using either the forced swim test or tail suspension test. We compared findings for different doses and time points and also drugs with different clinical profiles to investigate how well the outcomes in the rodent model predicted their effects in the clinic. Despite clear evidence that <i>N</i>-methyl-<i>D</i>-aspartate receptor antagonists reduce immobility time and hence exhibit an antidepressant profile in these tasks, we found similar effects with both clinically effective drugs as well as those which have failed to show efficacy in clinical trials. These findings suggest that behavioural despair tests in normal animals do not provide a good method to predict clinical efficacy of <i>N</i>-methyl-<i>D</i>-aspartate receptor antagonists.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":" ","pages":"23982128221081645"},"PeriodicalIF":0.0,"publicationDate":"2022-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48388728","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":"Climate crisis and ecological emergency: Why they concern (neuro)scientists, and what we can do.","authors":"Charlotte L Rae, Martin Farley, Kate J Jeffery, Anne E Urai","doi":"10.1177/23982128221075430","DOIUrl":"10.1177/23982128221075430","url":null,"abstract":"<p><p>Our planet is experiencing severe and accelerating climate and ecological breakdown caused by human activity. As professional scientists, we are better placed than most to understand the data that evidence this fact. However, like most other people, we ignore this inconvenient truth and lead our daily lives, at home and at work, as if these facts weren't true. In particular, we overlook that our own neuroscientific research practices, from our laboratory experiments to our often global travel, help drive climate change and ecosystem damage. We also hold privileged positions of authority in our societies but rarely speak out. Here, we argue that to help society create a survivable future, we neuroscientists can and must play our part. In April 2021, we delivered a symposium at the British Neuroscience Association meeting outlining what we think neuroscientists can and should do to help stop climate breakdown. Building on our talks (Box 1), we here outline what the climate and ecological emergencies mean for us as neuroscientists. We highlight the psychological mechanisms that block us from taking action, and then outline what practical steps we can take to overcome these blocks and work towards sustainability. In particular, we review environmental issues in neuroscience research, scientific computing, and conferences. We also highlight the key advocacy roles we can all play in our institutions and in society more broadly. The need for sustainable change has never been more urgent, and we call on all (neuro)scientists to act with the utmost urgency.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"6 1","pages":"23982128221075430"},"PeriodicalIF":0.0,"publicationDate":"2022-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45775368","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}