Neurobiology of Disease最新文献

{"title":"Phenotyping mitochondrial glutamyl-tRNA synthetase deficiency (EARS2): A case series and systematic literature review","authors":"Gonçalo Pelayo ,&nbsp;Margarida Paiva Coelho ,&nbsp;Joana Correia ,&nbsp;Anabela Bandeira ,&nbsp;Célia Nogueira ,&nbsp;Laura Vilarinho ,&nbsp;Esmeralda Martins","doi":"10.1016/j.nbd.2024.106644","DOIUrl":"10.1016/j.nbd.2024.106644","url":null,"abstract":"<div><p>Mitochondrial glutamyl-aminoacyl tRNA synthetase deficiency, stemming from biallelic mutations in the <em>EARS2</em> gene, was first described in 2012. With &lt;50 cases reported globally, this condition exhibits a distinct phenotype of neonatal or childhood-onset, often referred to as <em>leukoencephalopathy with thalamus and brainstem involvement and high lactate</em> (LTBL). It has also been one of the few reversible mitochondrial disorders described. The natural history of these patients is poorly documented, ranging from clinical and radiological improvement to early death.</p><p>Herein, we detail three cases from our centre, including follow-up on the Portuguese patient reported by Steenweg et al., These cases illustrate the phenotypic spectrum: i) rapidly progressive neonatal presentation with lactic acidemia and corpus callosum agenesis, leading to early death; ii) early onset with a severe, slowly progressive course; iii) early onset with a milder phenotype, showing some improvement and mild neurological symptoms. Additionally, we conducted a systematic literature review on cases of <em>EARS2-</em>deficient patients, focusing on clinical manifestations, laboratory findings, radiological aspects, and disease progression over time, along with respective data analysis. “Patients with EARS2 deficiency typically present within the first year of life with a well-defined neurometabolic disorder picture, often including hypotonia and/or spasticity, along with neurodevelopmental delay or regression. There are no pathognomonic features specific to EARS2 deficiency, and no genotype-phenotype correlation has been identified.” Comparing to initial characterization by Steenweg et al., this analysis reveals an expanded disease spectrum. We propose a novel strategy for clustering phenotypes into severe, moderate, or mild disease based on initial presentation, seemingly correlating with disease progression. The paucity of data on the disease's natural history highlights the need for a multicentric approach to enhance understanding and management.</p></div><div><h3>Take-home message</h3><p>Analysis of all cases published with EARS2 deficiency allows for establish disease spectrum and a novel strategy for clustering phenotypes which correlate to disease progression.</p></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"200 ","pages":"Article 106644"},"PeriodicalIF":5.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969996124002444/pdfft?md5=1c34ae68e8dc9b57a3698f8f71455abf&pid=1-s2.0-S0969996124002444-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum miR-34a-5p, miR-103a-3p, and miR-376a-3p as possible biomarkers of conversion from relapsing-remitting to secondary progressive multiple sclerosis","authors":"Simone Agostini ,&nbsp;Roberta Mancuso ,&nbsp;Lorenzo Agostino Citterio ,&nbsp;Domenico Caputo ,&nbsp;Letizia Oreni ,&nbsp;Riccardo Nuzzi ,&nbsp;Maria Barbara Pasanisi ,&nbsp;Marco Rovaris ,&nbsp;Mario Clerici","doi":"10.1016/j.nbd.2024.106648","DOIUrl":"10.1016/j.nbd.2024.106648","url":null,"abstract":"<div><p>Relapsing-remitting (RR) Multiple Sclerosis (MS) is the most common form of the disease; RRMS patients can maintain their clinical phenotype throughout life or can develop a secondary progressive (SP) course over time. We investigated whether circulating miRNAs can predict RR-to-SPMS conversion. A serum miRNAs profile was initially analyzed in a cross-sectional study by qPCR in 16 patients (8 RRMS and 8 SPMS) (Discovery cohort). Three miRNAs, i.e. miR-34a-5p, miR-103a-3p and miR-376a-3p, were significantly up-regulated in SPMS compared to RRMS patients (<em>p</em> &lt; 0.0 5). Serum concentration of the same miRNAs was subsequently analyzed in a retrospective study by ddPCR at baseline in 69 RRMS patients who did (<em>N</em> = 36 cSPMS) or did not (<em>N</em> = 33) convert into SPMS over a 10-year observation period (Study cohort). The results showed that these miRNAs were significantly increased at baseline only in those RRMS patients who converted to SPMS over time. miR-34a-5p and miR-376a-3p alone were significantly increased in cSPMS sera at the end of the 10-years period too. Serum concentration of miR-34a-5p, miR-103a-3p and miR-376a-3p is increased in RRMS patients several years before their conversion to SPMS. These miRNAs might be useful biomarkers to predict the conversion from RRMS to SPMS.</p></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"200 ","pages":"Article 106648"},"PeriodicalIF":5.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969996124002481/pdfft?md5=b0ff963a725ea21a798e59e03e74d872&pid=1-s2.0-S0969996124002481-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interactions of alpha-synuclein with membranes in Parkinson's disease: Mechanisms and therapeutic strategies","authors":"Baoyi Li ,&nbsp;Ulf Dettmer","doi":"10.1016/j.nbd.2024.106646","DOIUrl":"10.1016/j.nbd.2024.106646","url":null,"abstract":"<div><div>Parkinson's disease (PD), the second most common neurodegenerative disease worldwide, is marked by the presence of Lewy bodies and Lewy neurites, neuronal lesions containing large amounts of the synaptic protein alpha-synuclein (αS). While the underlying mechanisms of disease progression in PD remain unclear, increasing evidence supports the importance of interactions between αS and cellular membranes in PD pathology. Therefore, understanding the αS-membrane interplay in health and disease is crucial for the development of therapeutic strategies. In this review, we (1) discuss key scenarios of pathological αS-membrane interactions; (2) present in detail therapeutic strategies explicitly reported to modify αS-membrane interactions; and (3) introduce additional therapeutic strategies that may involve aspects of interfering with αS-membrane interaction. This way, we aim to provide a holistic perspective on this important aspect of disease-modifying strategies for PD and other α-synucleinopathies.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"201 ","pages":"Article 106646"},"PeriodicalIF":5.1,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in aperiodic and periodic EEG activity in young children with Down syndrome","authors":"McKena Geiger ,&nbsp;Sophie R. Hurewitz ,&nbsp;Katherine Pawlowski ,&nbsp;Nicole T. Baumer ,&nbsp;Carol L. Wilkinson","doi":"10.1016/j.nbd.2024.106643","DOIUrl":"10.1016/j.nbd.2024.106643","url":null,"abstract":"<div><p>Down syndrome (DS) is the most common cause of intellectual disability, yet little is known about the neurobiological pathways leading to cognitive impairments. Electroencephalographic (EEG) measures are commonly used to study neurodevelopmental disorders, but few studies have focused on young children with DS. Here we assess resting state EEG data collected from toddlers/preschoolers with DS (<em>n</em> = 29, age 13–48 months old) and compare their aperiodic and periodic EEG features with both age-matched (n = 29) and developmental-matched (<em>n</em> = 58) comparison groups. DS participants exhibited significantly reduced aperiodic slope, increased periodic theta power, and decreased alpha peak amplitude. A majority of DS participants displayed a prominent peak in the theta range, whereas a theta peak was not present in age-matched participants. Overall, similar findings were also observed when comparing DS and developmental-matched groups, suggesting that EEG differences are not explained by delayed cognitive ability.</p></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"200 ","pages":"Article 106643"},"PeriodicalIF":5.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969996124002432/pdfft?md5=f7f7b549af98f35097ce3bb7e70361b6&pid=1-s2.0-S0969996124002432-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current progress in microRNA profiling of circulating extracellular vesicles in amyotrophic lateral sclerosis: A systematic review","authors":"Yuji Ueno,&nbsp;Yuto Morishima,&nbsp;Takanori Hata,&nbsp;Atsuhiko Shindo,&nbsp;Hiroaki Murata,&nbsp;Tatsuya Saito,&nbsp;Yuki Nakamura,&nbsp;Kazumasa Shindo","doi":"10.1016/j.nbd.2024.106639","DOIUrl":"10.1016/j.nbd.2024.106639","url":null,"abstract":"<div><h3>Introduction</h3><p>Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting upper and lower motor neurons, leading to death resulting mainly from respiratory failure, for which there is currently no curative treatment. Underlying pathological mechanisms for the development of ALS are diverse and have yet to be elucidated. Non-invasive testing to isolate circulating molecules including microRNA to diagnose ALS has been reported, but circulating extracellular vesicle (EV)-derived microRNA has not been fully studied in the ALS population.</p></div><div><h3>Methods</h3><p>A systematic literature review to explore studies investigating the profile of microRNAs in EVs from blood samples of ALS patients was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.</p></div><div><h3>Results</h3><p>Eleven studies including a total of 263 patients with ALS were included in the present systematic review. The majority of patients had sporadic ALS, though a small number of patients with ALS having genetic mutations were included. Seven studies used plasma-derived EVs, and the remaining four studies used serum-derived EVs. RNA sequencing or microarrays were used in eight studies, and quantitative PCR was used in eight studies, of which five studies used RNA sequencing or microarrays for screening and quantitative PCR for validation. There was overlap of miR-199a-3p and miR-199a-5p in three studies.</p></div><div><h3>Conclusions</h3><p>Overall, the systematic review addressed the current advances in the profiling of microRNAs in circulating EVs of ALS patients. Blood samples, isolation of EVs, and microRNA analysis were diverse. Although there was an overlap of miR-199a-3p and miR-199a-5p, collection of further evidence is warranted.</p></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"200 ","pages":"Article 106639"},"PeriodicalIF":5.1,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969996124002390/pdfft?md5=1fb45ce4dc769c3cb65cd0d5ffc58bc8&pid=1-s2.0-S0969996124002390-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuromotor decline is associated with gut dysbiosis following surgical decompression for Degenerative Cervical Myelopathy","authors":"Pia M. Vidal ,&nbsp;Sydney Brockie ,&nbsp;Carlos Farkas ,&nbsp;James Hong ,&nbsp;Cindy Zhou ,&nbsp;Michael G. Fehlings","doi":"10.1016/j.nbd.2024.106640","DOIUrl":"10.1016/j.nbd.2024.106640","url":null,"abstract":"<div><p>Degenerative cervical myelopathy (DCM) describes a spectrum of disorders that cause progressive and chronic cervical spinal cord compression. The clinical presentation can be complex and can include locomotor impairment, hand and upper extremity dysfunction, pain, loss of bladder and bowel function, as well as gastrointestinal dysfunction. Once diagnosed, surgical decompression is the recommended treatment for DCM patients with moderate to severe impairment.</p><p>Our body is composed of a large community of microorganisms, known as the microbiota. Traumatic and non-traumatic spinal cord injuries (SCIs) can induce changes in the gut microbiota and gut microbiota derived metabolites. These changes have been reported as important disease-modifying factors after injury. However, whether gut dysbiosis is associated with functional neurological recovery after surgical decompression has not been examined to date.</p><p>Here, DCM was induced in C57BL/6 mice by implanting an aromatic polyether material underneath the C5–6 laminae. The extent of gut dysbiosis was assessed by gas chromatography and 16S rRNA sequencing from fecal samples before and after decompression. Neuromotor activity was assessed using the Catwalk test.</p><p>Our results show that DCM pre- and post- surgical decompression is associated with gut dysbiosis, without altering short chain fatty acids (SCFAs) levels. Significant differences in <em>Clostridia</em>, <em>Verrumicrobiae</em>, <em>Lachnospiracea</em>, <em>Firmicutes</em>, <em>Bacteroidales</em>, and <em>Clostridiaceae</em> were observed between the DCM group (before decompression) and after surgical decompression (2 and 5 weeks). The changes in gut microbiota composition correlated with locomotor features of the Catwalk. For example, a longer duration of ground contact and dysfunctional swing in the forelimbs, were positively correlated with gut dysbiosis. These results show for the first time an association between gut dysbiosis and locomotor deterioration after delayed surgical decompression. Thus, providing a better understanding of the extent of changes in microbiota composition in the setting of DCM pre- and post- surgical decompression.</p></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"200 ","pages":"Article 106640"},"PeriodicalIF":5.1,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969996124002407/pdfft?md5=5162e5c3771e41786d87a1924a8fac11&pid=1-s2.0-S0969996124002407-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An emerging role of STriatal-Enriched protein tyrosine Phosphatase in hyperexcitability-associated brain disorders","authors":"Jennifer M. Walters ,&nbsp;Hayden A. Noblet ,&nbsp;Hee Jung Chung","doi":"10.1016/j.nbd.2024.106641","DOIUrl":"10.1016/j.nbd.2024.106641","url":null,"abstract":"<div><p>STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-specific tyrosine phosphatase that is associated with numerous neurological and neuropsychiatric disorders. STEP dephosphorylates and inactivates various kinases and phosphatases critical for neuronal function and health including Fyn, Pyk2, ERK1/2, p38, and PTPα. Importantly, STEP dephosphorylates NMDA and AMPA receptors, two major glutamate receptors that mediate fast excitatory synaptic transmission. This STEP-mediated dephosphorylation leads to their internalization and inhibits both Hebbian synaptic potentiation and homeostatic synaptic scaling. Hence, STEP has been widely accepted to weaken excitatory synaptic strength. However, emerging evidence implicates a novel role of STEP in neuronal hyperexcitability and seizure disorders. Genetic deletion and pharmacological blockade of STEP reduces seizure susceptibility in acute seizure mouse models and audiogenic seizures in a mouse model of Fragile X syndrome. Pharmacologic inhibition of STEP also decreases hippocampal activity and neuronal intrinsic excitability. Here, we will highlight the divergent roles of STEP in excitatory synaptic transmission and neuronal intrinsic excitability, present the potential underlying mechanisms, and discuss their impact on STEP-associated neurologic and neuropsychiatric disorders.</p></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"200 ","pages":"Article 106641"},"PeriodicalIF":5.1,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969996124002419/pdfft?md5=671cea23b94e0de928314fbe8320e884&pid=1-s2.0-S0969996124002419-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142004869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations in DNA 5-hydroxymethylation patterns in the hippocampus of an experimental model of chronic epilepsy","authors":"Rudhab Bahabry ,&nbsp;Rebecca M. Hauser ,&nbsp;Richard G. Sánchez ,&nbsp;Silvienne Sint Jago ,&nbsp;Lara Ianov ,&nbsp;Remy J. Stuckey ,&nbsp;R. Ryley Parrish ,&nbsp;Lawrence Ver Hoef ,&nbsp;Farah D. Lubin","doi":"10.1016/j.nbd.2024.106638","DOIUrl":"10.1016/j.nbd.2024.106638","url":null,"abstract":"<div><p>Temporal lobe epilepsy (TLE) is a type of focal epilepsy characterized by spontaneous recurrent seizures originating from the hippocampus. The epigenetic reprogramming hypothesis of epileptogenesis suggests that the development of TLE is associated with alterations in gene transcription changes resulting in a hyperexcitable network in TLE. DNA 5-methylcytosine (5-mC) is an epigenetic mechanism that has been associated with chronic epilepsy. However, the contribution of 5-hydroxymethylcytosine (5-hmC), a product of 5-mC demethylation by the Ten-Eleven Translocation (TET) family proteins in chronic TLE is poorly understood. 5-hmC is abundant in the brain and acts as a stable epigenetic mark altering gene expression through several mechanisms. Here, we found that the levels of bulk DNA 5-hmC but not 5-mC were significantly reduced in the hippocampus of human TLE patients and in the kainic acid (KA) TLE rat model. Using 5-hmC hMeDIP-sequencing, we characterized 5-hmC distribution across the genome and found bidirectional regulation of 5-hmC at intergenic regions within gene bodies. We found that hypohydroxymethylated 5-hmC intergenic regions were associated with several epilepsy-related genes, including <em>Gal</em>, <em>SV2,</em> and <em>Kcnj11</em> and hyperdroxymethylation 5-hmC intergenic regions were associated with <em>Gad65</em>, <em>TLR4</em>, and <em>Bdnf</em> gene expression. Mechanistically, <em>Tet1</em> knockdown in the hippocampus was sufficient to decrease 5-hmC levels and increase seizure susceptibility following KA administration. In contrast, <em>Tet1</em> overexpression in the hippocampus resulted in increased 5-hmC levels associated with improved seizure resiliency in response to KA. These findings suggest an important role for 5-hmC as an epigenetic regulator of epilepsy that can be manipulated to influence seizure outcomes.</p></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"200 ","pages":"Article 106638"},"PeriodicalIF":5.1,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969996124002389/pdfft?md5=e28c9c9f9a6f45a11455c11eb6308f66&pid=1-s2.0-S0969996124002389-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotyping of FGF12AV52H mutation in mouse implies a complex FGF12 network","authors":"Jianyu Huang ,&nbsp;Chongyang Sun ,&nbsp;Qian Zhu ,&nbsp;Ge Wu ,&nbsp;Yi Cao ,&nbsp;Jiarui Shi ,&nbsp;Shuyu He ,&nbsp;Luyao Jiang ,&nbsp;Jianxiang Liao ,&nbsp;Lin Li ,&nbsp;Cheng Zhong ,&nbsp;Yi Lu","doi":"10.1016/j.nbd.2024.106637","DOIUrl":"10.1016/j.nbd.2024.106637","url":null,"abstract":"<div><p>Pathogenic missense mutation of the <em>FGF12</em> gene is responsible for a variable disease phenotypic spectrum. Disease-specific therapies require precise dissection of the relationship between different mutations and phenotypes. The lack of a proper animal model hinders the investigation of related diseases, such as early-onset epileptic encephalopathy. Here, an FGF12A^V52H mouse model was generated using CRISPR/Cas9 technology, which altered the A isoform without affecting the B isoform. The FGF12A^V52H mice exhibited seizure susceptibility, while no spontaneous seizures were observed. The increased excitability in dorsal hippocampal CA3 neurons was confirmed by patch-clamp recordings. Furthermore, immunostaining showed that the balance of excitatory/inhibitory neurons in the hippocampus of the FGF12A^V52H mice was perturbed. The increases in inhibitory SOM+ neurons and excitatory CaMKII+ neurons were heterogeneous. Moreover, the locomotion, anxiety levels, risk assessment behavior, social behavior, and cognition of the FGF12A^V52H mice were investigated by elevated plus maze, open field, three-chamber sociability, and novel object tests, respectively. Cognition deficit, impaired risk assessment, and social behavior with normal social indexes were observed, implying complex consequences of V52H FGF12A in mice. Together, these data suggest that the function of FGF12A in neurons can be immediate or long-term and involves modulation of ion channels and the differentiation and maturation of neurons. The FGF12A^V52H mouse model increases the understanding of the function of FGF12A, and it is of great importance for revealing the complex network of the <em>FGF12</em> gene in physiological and pathological processes.</p></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"200 ","pages":"Article 106637"},"PeriodicalIF":5.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969996124002377/pdfft?md5=c2b8e98893a556e96bf5c6d50a41151d&pid=1-s2.0-S0969996124002377-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the heart-brain and brain-heart axes: Insights from a bidirectional Mendelian randomization study on brain cortical structure and cardiovascular disease","authors":"Guang-zhi Liao ,&nbsp;Chun-hui He ,&nbsp;Xin-qing Li ,&nbsp;Yang Xiong ,&nbsp;Li-yan Huang ,&nbsp;An-ran Xin ,&nbsp;Guo Ai ,&nbsp;Man-qing Luo ,&nbsp;Yu-hui Zhang ,&nbsp;Jian Zhang","doi":"10.1016/j.nbd.2024.106636","DOIUrl":"10.1016/j.nbd.2024.106636","url":null,"abstract":"<div><h3>Introduction</h3><p>The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored.</p></div><div><h3>Methods</h3><p>This study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures.</p></div><div><h3>Results</h3><p>A total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q&lt;0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation.</p></div><div><h3>Conclusion</h3><p>The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.</p></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"200 ","pages":"Article 106636"},"PeriodicalIF":5.1,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969996124002365/pdfft?md5=cd4d8aba5a6abc203083b2fa2efd01bc&pid=1-s2.0-S0969996124002365-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}