Experimental Neurobiology最新文献_第6页

Lactobacillus reuteri ATG-F4 Alleviates Chronic Stress-induced Anhedonia by Modulating the Prefrontal Serotonergic System. 路氏乳杆菌ATG-F4通过调节额前血清素能系统来缓解慢性应激诱导的享乐主义。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2023-10-31 DOI: 10.5607/en23028

Jiyun Lee, Eum-Ji Kim, Gun-Seok Park, Jeongseop Kim, Tae-Eun Kim, Yoo Jin Lee, Juyi Park, Jihee Kang, Ja Wook Koo, Tae-Yong Choi

{"title":"Lactobacillus reuteri ATG-F4 Alleviates Chronic Stress-induced Anhedonia by Modulating the Prefrontal Serotonergic System.","authors":"Jiyun Lee, Eum-Ji Kim, Gun-Seok Park, Jeongseop Kim, Tae-Eun Kim, Yoo Jin Lee, Juyi Park, Jihee Kang, Ja Wook Koo, Tae-Yong Choi","doi":"10.5607/en23028","DOIUrl":"10.5607/en23028","url":null,"abstract":"Mental health is influenced by the gut-brain axis; for example, gut dysbiosis has been observed in patients with major depressive disorder (MDD). Gut microbial changes by fecal microbiota transplantation or probiotics treatment reportedly modulates depressive symptoms. However, it remains unclear how gut dysbiosis contributes to mental dysfunction, and how correction of the gut microbiota alleviates neuropsychiatric disorders. Our previous study showed that chronic consumption of Lactobacillus reuteri ATG-F4 (F4) induced neurometabolic alterations in healthy mice. Here, we investigated whether F4 exerted therapeutic effects on depressive-like behavior by influencing the central nervous system. Using chronic unpredictable stress (CUS) to induce anhedonia, a key symptom of MDD, we found that chronic F4 consumption alleviated CUS-induced anhedonic behaviors, accompanied by biochemical changes in the gut, serum, and brain. Serum and brain metabolite concentrations involved in tryptophan metabolism were regulated by CUS and F4. F4 consumption reduced the elevated levels of serotonin (5-HT) in the brain observed in the CUS group. Additionally, the increased expression of Htr1a, a subtype of the 5-HT receptor, in the medial prefrontal cortex (mPFC) of stressed mice was restored to levels observed in stress-naïve mice following F4 supplementation. We further demonstrated the role of Htr1a using AAV-shRNA to downregulate Htr1a in the mPFC of CUS mice, effectively reversing CUS-induced anhedonic behavior. Together, our findings suggest F4 as a potential therapeutic approach for relieving some depressive symptoms and highlight the involvement of the tryptophan metabolism in mitigating CUS-induced depressive-like behaviors through the action of this bacterium.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 5","pages":"313-327"},"PeriodicalIF":2.4,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Methylation-based Subclassifications of Embryonal Tumor with Multilayered Rosettes in Not Just Pediatric Brains. 基于甲基化的胚胎肿瘤亚类与多层玫瑰不仅在儿童大脑中。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2023-10-31 DOI: 10.5607/en23021

Eric Eunshik Kim, Kwanghoon Lee, Ji-Hoon Phi, Min-Sung Kim, Hyoung Jin Kang, Hongseok Yun, Sung-Hye Park

{"title":"Methylation-based Subclassifications of Embryonal Tumor with Multilayered Rosettes in Not Just Pediatric Brains.","authors":"Eric Eunshik Kim, Kwanghoon Lee, Ji-Hoon Phi, Min-Sung Kim, Hyoung Jin Kang, Hongseok Yun, Sung-Hye Park","doi":"10.5607/en23021","DOIUrl":"10.5607/en23021","url":null,"abstract":"The aim of this study is to investigate the genetic profiles and methylation-based classifications of Embryonal tumor with multilayered rosettes (ETMR), with a specific focus on differentiating between C19MC amplified and C19MC-not amplified groups, including cases with DICER1 mutations. To achieve this, next-generation sequencing using a targeted gene panel for brain tumors and methylation class studies using the Epic850K microarray were performed to identify tumor subclasses and their clinicopathological characteristics. The study cohort consisted of four patients, including 3 children (a 4-months/F, a 9-months/M, and a 2 y/F), and one adult (a 30 y/Male). All three tumors in the pediatric patients originated in the posterior fossa and exhibited TTYH1:C19MC fusion and C19MC amplification. The fourth case in the adult patient involved the cerebellopontine angle with biallelic DICER1 mutation. Histopathological examination revealed typical embryonal features characterized by multilayered rosettes and abundant neuropils in all cases, while the DICER1-mutant ETMR also displayed cartilage islands in addition to the classic ETMR pathology. All four tumors showed positive staining for LIN28A. The t-SNE clustering analysis demonstrated that the first three cases clustered with known subtypes of ETMR, specifically C19MC amplified, while the fourth case clustered separately to non-C19MC amplified subclass. During the follow-up period of 6~12 months, leptomeningeal dissemination of the tumor occurred in all patients. Considering the older age of onset in DICER1-mutant ETMR, genetic counseling should be recommended due to the association of DICER1 mutations with germline and second-hit somatic mutations in cancer.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 5","pages":"354-361"},"PeriodicalIF":2.4,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Graph Theoretical Analysis of Brain Structural Connectivity in Patients with Alcohol Dependence. 酒精依赖患者大脑结构连接的图论分析。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2023-10-31 DOI: 10.5607/en23026

Hyunjung Lee, Joon Hyung Jung, Seungwon Chung, Gawon Ju, Siekyeong Kim, Jung-Woo Son, Chul-Jin Shin, Sang Ick Lee, Jeonghwan Lee

{"title":"Graph Theoretical Analysis of Brain Structural Connectivity in Patients with Alcohol Dependence.","authors":"Hyunjung Lee, Joon Hyung Jung, Seungwon Chung, Gawon Ju, Siekyeong Kim, Jung-Woo Son, Chul-Jin Shin, Sang Ick Lee, Jeonghwan Lee","doi":"10.5607/en23026","DOIUrl":"10.5607/en23026","url":null,"abstract":"This study aimed to compare brain structural connectivity using graph theory between patients with alcohol dependence and social drinkers. The participants were divided into two groups; the alcohol group (N=23) consisting of patients who had been hospitalized and had abstained from alcohol for at least three months and the control group (N=22) recruited through advertisements and were social drinkers. All participants were evaluated using 3T magnetic resonance imaging. A total of 1000 repeated whole-brain tractographies with random parameters were performed using DSI Studio. Four hundred functionally defined cortical regions of interest (ROIs) were parcellated using FreeSurfer based on the Schaefer Atlas. The ROIs were overlaid on the tractography results to generate 1000 structural connectivity matrices per person, and 1000 matrices were averaged into a single matrix per subject. Graph analysis was performed through igraph R package. Graph measures were compared between the two groups using analysis of covariance, considering the effects of age and smoking pack years. The alcohol group showed lower local efficiency than the control group in the whole-brain (F=5.824, p=0.020), somato-motor (F=5.963, p=0.019), and default mode networks (F=4.422, p=0.042). The alcohol group showed a lower global efficiency (F=5.736, p=0.021) in the control network. The transitivity of the alcohol group in the dorsal attention network was higher than that of the control (F=4.257, p=0.046). Our results imply that structural stability of the whole-brain network is affected in patients with alcohol dependence, which can lead to ineffective information processing in cases of local node failure.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 5","pages":"362-369"},"PeriodicalIF":2.4,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BDNF/TrkB Signaling Inhibition Suppresses Astrogliosis and Alleviates Mechanical Allodynia in a Partial Crush Injury Model. BDNF/TrkB信号抑制抑制部分挤压损伤模型中的星形胶质细胞增生和减轻机械性异常疼痛。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2023-10-31 DOI: 10.5607/en23031

Tien Thuy Phan, Nishani Jayanika Jayathilake, Kyu Pil Lee, Joo Min Park

{"title":"BDNF/TrkB Signaling Inhibition Suppresses Astrogliosis and Alleviates Mechanical Allodynia in a Partial Crush Injury Model.","authors":"Tien Thuy Phan, Nishani Jayanika Jayathilake, Kyu Pil Lee, Joo Min Park","doi":"10.5607/en23031","DOIUrl":"10.5607/en23031","url":null,"abstract":"Neuropathic pain presents a formidable clinical challenge due to its persistent nature and limited responsiveness to conventional analgesic treatments. While significant progress has been made in understanding the role of spinal astrocytes in neuropathic pain, their contribution and functional changes following a partial crush injury (PCI) remain unexplored. In this study, we investigated structural and functional changes in spinal astrocytes during chronic neuropathic pain, employing a partial crush injury model. This model allowes us to replicate the transition from initial nociceptive responses to persistent pain, highlighting the relevance of astrocytes in pain maintenance and sensitization. Through the examination of mechanical allodynia, a painful sensation in response to innocuous stimuli, and the correlation with increased levels of brain-derived neurotrophic factor (BDNF) along with reactive astrocytes, we identified a potential mechanistic link between astrocytic activity and BDNF signaling. Ultimately, our research provides evidence that inhibiting astrocyte activation through a BDNF/TrkB inhibitor alleviates mechanical allodynia, underscoring the therapeutic potential of targeting glial BDNF-related pathways for pain management. These findings offer critical insights into the cellular and molecular dynamics of neuropathic pain, paving the way for innovative and targeted treatment strategies for this challenging condition.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 5","pages":"343-353"},"PeriodicalIF":2.4,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71479886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single Versus Repetitive Traumatic Brain Injury: Current Knowledge on the Chronic Outcomes, Neuropathology and the Role of TDP-43 Proteinopathy. 单次和重复性创伤性脑损伤：关于慢性结局、神经病理学和TDP-43蛋白病作用的最新知识。

IF 1.8 4区医学

Experimental Neurobiology Pub Date : 2023-08-31 DOI: 10.5607/en23008

Tamara Janković, Kristina Pilipović

{"title":"Single Versus Repetitive Traumatic Brain Injury: Current Knowledge on the Chronic Outcomes, Neuropathology and the Role of TDP-43 Proteinopathy.","authors":"Tamara Janković, Kristina Pilipović","doi":"10.5607/en23008","DOIUrl":"10.5607/en23008","url":null,"abstract":"Traumatic brain injury (TBI) is one of the most important causes of death and disability in adults and thus an important public health problem. Following TBI, secondary pathophysiological processes develop over time and condition the development of different neurodegenerative entities. Previous studies suggest that neurobehavioral changes occurring after a single TBI are the basis for the development of Alzheimer's disease, while repetitive TBI is considered to be a contributing factor for chronic traumatic encephalopathy development. However, pathophysiological processes that determine the evolvement of a particular chronic entity are still unclear. Human post-mortem studies have found combinations of amyloid, tau, Lewi bodies, and TAR DNA-binding protein 43 (TDP-43) pathologies after both single and repetitive TBI. This review focuses on the pathological changes of TDP-43 after single and repetitive brain traumas. Numerous studies have shown that TDP-43 proteinopathy noticeably occurs after repetitive head trauma. A relatively small number of available preclinical research on single brain injury are not in complete agreement with the results from the human samples, which makes it difficult to draw specific conclusions. Also, as TBI is considered a heterogeneous type of injury, different experimental trauma models and injury intensities may cause differences in the cascade of secondary injury, which should be considered in future studies. Experimental and post-mortem studies of TDP-43 pathobiology should be carried out, preferably in the same laboratories, to determine its involvement in the development of neurodegenerative conditions after one and repetitive TBI, especially in the context of the development of new therapeutic options.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 4","pages":"195-215"},"PeriodicalIF":1.8,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/49/40/en-32-4-195.PMC10569144.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41107867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NAG-1/GDF-15 Transgenic Female Mouse Shows Delayed Peak Period of the Second Phase Nociception in Formalin-induced Inflammatory Pain. NAG-1/GDF-15转基因雌性小鼠在福尔马林诱导的炎症性疼痛中表现出第二阶段伤害感受的延迟峰值期。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2023-08-31 DOI: 10.5607/en23019

Sheu-Ran Choi, Jaehak Lee, Ji-Young Moon, Seung Joon Baek, Jang-Hern Lee

{"title":"NAG-1/GDF-15 Transgenic Female Mouse Shows Delayed Peak Period of the Second Phase Nociception in Formalin-induced Inflammatory Pain.","authors":"Sheu-Ran Choi, Jaehak Lee, Ji-Young Moon, Seung Joon Baek, Jang-Hern Lee","doi":"10.5607/en23019","DOIUrl":"10.5607/en23019","url":null,"abstract":"Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1), also known as growth differentiation factor-15 (GDF-15), is associated with cancer, diabetes, and inflammation, while there is limited understanding of the role of NAG-1 in nociception. Here, we examined the nociceptive behaviors of NAG-1 transgenic (TG) mice and wild-type (WT) littermates. Mechanical sensitivity was evaluated by using the von Frey filament test, and thermal sensitivity was assessed by the hot-plate, Hargreaves, and acetone tests. c-Fos, glial fibrillary acidic protein (GFAP), and ionized calcium binding adaptor molecule-1 (Iba-1) immunoreactivity was examined in the spinal cord following observation of the formalin-induced nociceptive behaviors. There was no difference in mechanical or thermal sensitivity for NAG-1 TG and WT mice. Intraplantar formalin injection induced nociceptive behaviors in both male and female NAG-1 TG and WT mice. The peak period in the second phase was delayed in NAG-1 TG female mice compared with that of WT female mice, while there was no difference in the cumulative time of nociceptive behaviors between the two groups of mice. Formalin increased spinal c-Fos immunoreactivity in both TG and WT female mice. Neither GFAP nor Iba-1 immunoreactivity was increased in the spinal cord of TG and WT female mice. These findings indicate that NAG-1 TG mice have comparable baseline sensitivity to mechanical and thermal stimulation as WT mice and that NAG-1 in female mice may have an inhibitory effect on the second phase of inflammatory pain. Therefore, it could be a novel target to inhibit central nervous system response in pain.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 4","pages":"247-258"},"PeriodicalIF":2.4,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b2/bb/en-32-4-247.PMC10569140.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41117951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bias in Prestimulus Motor Cortical Activity Determines Decision-making Error in Rodents. 刺激前运动皮层活动的偏差决定啮齿动物的决策错误。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2023-08-31 DOI: 10.5607/en23020

Soyoung Chae, Duho Sihn, Sung-Phil Kim

{"title":"Bias in Prestimulus Motor Cortical Activity Determines Decision-making Error in Rodents.","authors":"Soyoung Chae, Duho Sihn, Sung-Phil Kim","doi":"10.5607/en23020","DOIUrl":"10.5607/en23020","url":null,"abstract":"Decision-making is a complex process that involves the integration and interpretation of sensory information to guide actions. The rodent motor cortex, which is generally involved in motor planning and execution, also plays a critical role in decision-making processes. In perceptual delayed-response tasks, the rodent motor cortex can represent sensory cues, as well as the decision of where to move. However, it remains unclear whether erroneous decisions arise from incorrect encoding of sensory information or improper utilization of the collected sensory information in the motor cortex. In this study, we analyzed the rodent anterior lateral motor cortex (ALM) while the mice performed perceptual delayed-response tasks. We divided population activities into sensory and choice signals to separately examine the encoding and utilization of sensory information. We found that the encoding of sensory information in the error trials was similar to that in the hit trials, whereas choice signals evolved differently between the error and hit trials. In error trials, choice signals displayed an offset in the opposite direction of instructed licking even before stimulus presentation, and this tendency gradually increased after stimulus onset, leading to incorrect licking. These findings suggest that decision errors are caused by biases in choice-related activities rather than by incorrect sensory encoding. Our study elaborates on the understanding of decision-making processes by providing neural substrates for erroneous decisions.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 4","pages":"271-284"},"PeriodicalIF":2.4,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f8/e1/en-32-4-271.PMC10569143.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Global Cerebral Ischemia-induced Depression Accompanies Alteration of Neuronal Excitability in the Infralimbic Cortex Layer 2/3 Pyramidal Neurons. 全脑缺血诱导的抑郁症伴随边缘下皮层2/3锥体神经元兴奋性的改变。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2023-08-31 DOI: 10.5607/en23017

Dong Cheol Jang, Seunghwan Choi, Geehoon Chung, Sun Kwang Kim

{"title":"Global Cerebral Ischemia-induced Depression Accompanies Alteration of Neuronal Excitability in the Infralimbic Cortex Layer 2/3 Pyramidal Neurons.","authors":"Dong Cheol Jang, Seunghwan Choi, Geehoon Chung, Sun Kwang Kim","doi":"10.5607/en23017","DOIUrl":"10.5607/en23017","url":null,"abstract":"Cerebral ischemia can lead to a range of sequelae, including depression. The pathogenesis of depression involves neuronal change of the medial prefrontal cortex (mPFC). However, how cerebral ischemia-induced changes manifest across subregions and layers of the mPFC is not well understood. In this study, we induced cerebral ischemia in mice via transient bilateral common carotid artery occlusion (tBCCAO) and observed depressive-like behavior. Using whole-cell patch clamp recording, we identified changes in the excitability of pyramidal neurons in the prelimbic cortex (PL) and infralimbic cortex (IL), the subregions of mPFC. Compared to sham control mice, tBCCAO mice showed significantly reduced neuronal excitability in IL layer 2/3 but not layer 5 pyramidal neurons, accompanied by increased rheobase current and decreased input resistance. In contrast, no changes were observed in the excitability of PL layer 2/3 and layer 5 pyramidal neurons. Our results provide a new direction for studying the pathogenesis of depression following ischemic damage by showing that cerebral ischemia induces subregion- and layer-specific changes in the mPFC pyramidal neurons.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 4","pages":"302-312"},"PeriodicalIF":2.4,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/da/bf/en-32-4-302.PMC10569139.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41125014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Advances in Amyloid-β Clearance in the Brain and Periphery: Implications for Neurodegenerative Diseases. 脑和外周淀粉样蛋白-β清除的研究进展：对神经退行性疾病的意义。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2023-08-31 DOI: 10.5607/en23014

Rahat Ullah, Eun Jeong Lee

{"title":"Advances in Amyloid-β Clearance in the Brain and Periphery: Implications for Neurodegenerative Diseases.","authors":"Rahat Ullah, Eun Jeong Lee","doi":"10.5607/en23014","DOIUrl":"10.5607/en23014","url":null,"abstract":"This review examines the role of impaired amyloid-β clearance in the accumulation of amyloid-β in the brain and the periphery, which is closely associated with Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). The molecular mechanism underlying amyloid-β accumulation is largely unknown, but recent evidence suggests that impaired amyloid-β clearance plays a critical role in its accumulation. The review provides an overview of recent research and proposes strategies for efficient amyloid-β clearance in both the brain and periphery. The clearance of amyloid-β can occur through enzymatic or non-enzymatic pathways in the brain, including neuronal and glial cells, blood-brain barrier, interstitial fluid bulk flow, perivascular drainage, and cerebrospinal fluid absorption-mediated pathways. In the periphery, various mechanisms, including peripheral organs, immunomodulation/immune cells, enzymes, amyloid-β-binding proteins, and amyloid-β-binding cells, are involved in amyloid-β clearance. Although recent findings have shed light on amyloid-β clearance in both regions, opportunities remain in areas where limited data is available. Therefore, future strategies that enhance amyloid-β clearance in the brain and/or periphery, either through central or peripheral clearance approaches or in combination, are highly encouraged. These strategies will provide new insight into the disease pathogenesis at the molecular level and explore new targets for inhibiting amyloid-β deposition, which is central to the pathogenesis of sporadic AD (amyloid-β in parenchyma) and CAA (amyloid-β in blood vessels).","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 4","pages":"216-246"},"PeriodicalIF":2.4,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/bf/en-32-4-216.PMC10569141.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41103914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Presenilin 2 N141I Mutation Induces Hyperimmunity by Immune Cell-specific Suppression of REV-ERBα without Altering Central Circadian Rhythm. 早老素2 N141I突变通过免疫细胞特异性抑制REV-ERBα而不改变中枢昼夜节律诱导高免疫。

IF 2.4 4区医学

Experimental Neurobiology Pub Date : 2023-08-31 DOI: 10.5607/en23012

Hyeri Nam, Boil Kim, Younghwan Lee, Han Kyoung Choe, Seong-Woon Yu

{"title":"Presenilin 2 N141I Mutation Induces Hyperimmunity by Immune Cell-specific Suppression of REV-ERBα without Altering Central Circadian Rhythm.","authors":"Hyeri Nam, Boil Kim, Younghwan Lee, Han Kyoung Choe, Seong-Woon Yu","doi":"10.5607/en23012","DOIUrl":"10.5607/en23012","url":null,"abstract":"Circadian rhythm is a 24-hour cycle of behavioral and physiological changes. Disrupted sleep-wake patterns and circadian dysfunction are common in patients of Alzheimer Disease (AD) and are closely related with neuroinflammation. However, it is not well known how circadian rhythm of immune cells is altered during the progress of AD. Previously, we found presenilin 2 (Psen2) N141I mutation, one of familial AD (FAD) risk genes, induces hyperimmunity through the epigenetic repression of REV-ERBα expression in microglia and bone marrow-derived macrophage (BMDM) cells. Here, we investigated whether repression of REV-ERBα is associated with dysfunction of immune cell-endogenous or central circadian rhythm by analyses of clock genes expression and cytokine secretion, bioluminescence recording of rhythmic PER2::LUC expression, and monitoring of animal behavioral rhythm. Psen2 N141I mutation down-regulated REV-ERBα and induced selective over-production of IL-6 (a well-known clock-dependent cytokine) following the treatment of toll-like receptor (TLR) ligands in microglia, astrocytes, and BMDM. Psen2 N141I mutation also lowered amplitude of intrinsic daily oscillation in these immune cells representatives of brain and periphery. Of interest, however, the period of daily rhythm remained intact in immune cells. Furthermore, analyses of the central clock and animal behavioral rhythms revealed that central clock remained normal without down-regulation of REV-ERBα. These results suggest that Psen2 N141I mutation induces hyperimmunity mainly through the suppression of REV-ERBα in immune cells, which have lowered amplitude but normal period of rhythmic oscillation. Furthermore, our data reveal that central circadian clock is not affected by Psen2 N141I mutation.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"32 4","pages":"259-270"},"PeriodicalIF":2.4,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ee/9b/en-32-4-259.PMC10569138.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41094541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0