Seunghyuk Kim, Heeyoung Park, Jieun Kang, Seunghyuk Choi, Ali Sadra, Sung-Oh Huh
β-PIX, a Rac1/Cdc42-specific guanine nucleotide exchange factor, is known to regulate actin cytoskeleton remodeling during cell migration. In this study, we investigated the effects of β-PIX-d, an isoform of β-PIX, on neocortical development and neuritogenesis. Overexpression of β-PIX-d in the embryonic neocortex induced increased cell clusters and enhanced neurite outgrowth in cortical neurons. Following in utero electroporation of β-PIX-d expression vectors into neuronal progenitor cells at embryonic day 13.5 (E13.5), histological analysis at postnatal day 0 (P0) revealed the presence of clustered neurons and neurites outside of the marginal zone (MZ). Immunofluorescence staining with the neuronal marker TuJ1 confirmed that the clustered structures were predominantly composed of neurons. Layer-specific marker analysis further demonstrated the misplacement of layer V-VI neurons into layer I and the subarachnoid space. In primary neocortical cultures, β-PIX-d overexpression promoted neuritogenesis and increased Rac1 activity, as detected by pull-down assays. These findings suggest that β-PIX-d and Rac1 interactions play a critical role in the formation of neocortical clustering and the regulation of neuritogenesis.
{"title":"β-PIX-d, a Member of the ARHGEF7 Guanine Nucleotide Exchange Factor Family, Activates Rac1 and Induces Neuritogenesis in Primary Cortical Neurons.","authors":"Seunghyuk Kim, Heeyoung Park, Jieun Kang, Seunghyuk Choi, Ali Sadra, Sung-Oh Huh","doi":"10.5607/en24026","DOIUrl":"10.5607/en24026","url":null,"abstract":"<p><p>β-PIX, a Rac1/Cdc42-specific guanine nucleotide exchange factor, is known to regulate actin cytoskeleton remodeling during cell migration. In this study, we investigated the effects of β-PIX-d, an isoform of β-PIX, on neocortical development and neuritogenesis. Overexpression of β-PIX-d in the embryonic neocortex induced increased cell clusters and enhanced neurite outgrowth in cortical neurons. Following in utero electroporation of β-PIX-d expression vectors into neuronal progenitor cells at embryonic day 13.5 (E13.5), histological analysis at postnatal day 0 (P0) revealed the presence of clustered neurons and neurites outside of the marginal zone (MZ). Immunofluorescence staining with the neuronal marker TuJ1 confirmed that the clustered structures were predominantly composed of neurons. Layer-specific marker analysis further demonstrated the misplacement of layer V-VI neurons into layer I and the subarachnoid space. In primary neocortical cultures, β-PIX-d overexpression promoted neuritogenesis and increased Rac1 activity, as detected by pull-down assays. These findings suggest that β-PIX-d and Rac1 interactions play a critical role in the formation of neocortical clustering and the regulation of neuritogenesis.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"33 5","pages":"215-224"},"PeriodicalIF":1.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681194","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}
Kwangsu Kim, Jisub Bae, JeeWon Lee, Sun Ae Moon, Sang-Ho Lee, Won-Seok Kang, Cheil Moon
Although we have multiple senses, multimedia mainly targets vision and olfaction. To expand the senses impacted by multimedia, olfactory stimulation has been used to enhance the sense of reality. Odors are primarily matched with objects in scenes. However, it is impractical to select all odors that match all objects in a scene and offer them to viewers. As an alternative, offering a single odor in a category as representative of other odors belonging to that category has been suggested. However, it is unclear whether viewers' responses to videos with multiple odors (e.g., rose, lavender, and lily) from a category (e.g., flowers) are comparable. Therefore, we studied whether odors belonging to a given category could be similar in behavioral congruency and in the five frequency bands (delta, theta, alpha, beta, and gamma) of electroencephalogram (EEG) data collected while viewers watched videos. We conducted questionnaires and EEG experiments to understand the effects of similar odors belonging to categories. Our results showed that similar odors in a specific odor category were more congruent with videos than those in different odor categories. In our EEG data, the delta and theta bands were mainly clustered when odors were offered to viewers in similar categories. The theta band is known to be primarily related to the neural signals of odor information. Our studies showed that choosing odors based on odor categories in multimedia can be feasible.
{"title":"The Impact of Odor Category Similarity on Multimedia Experience.","authors":"Kwangsu Kim, Jisub Bae, JeeWon Lee, Sun Ae Moon, Sang-Ho Lee, Won-Seok Kang, Cheil Moon","doi":"10.5607/en24020","DOIUrl":"10.5607/en24020","url":null,"abstract":"<p><p>Although we have multiple senses, multimedia mainly targets vision and olfaction. To expand the senses impacted by multimedia, olfactory stimulation has been used to enhance the sense of reality. Odors are primarily matched with objects in scenes. However, it is impractical to select all odors that match all objects in a scene and offer them to viewers. As an alternative, offering a single odor in a category as representative of other odors belonging to that category has been suggested. However, it is unclear whether viewers' responses to videos with multiple odors (e.g., rose, lavender, and lily) from a category (e.g., flowers) are comparable. Therefore, we studied whether odors belonging to a given category could be similar in behavioral congruency and in the five frequency bands (delta, theta, alpha, beta, and gamma) of electroencephalogram (EEG) data collected while viewers watched videos. We conducted questionnaires and EEG experiments to understand the effects of similar odors belonging to categories. Our results showed that similar odors in a specific odor category were more congruent with videos than those in different odor categories. In our EEG data, the delta and theta bands were mainly clustered when odors were offered to viewers in similar categories. The theta band is known to be primarily related to the neural signals of odor information. Our studies showed that choosing odors based on odor categories in multimedia can be feasible.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"33 5","pages":"238-250"},"PeriodicalIF":1.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681192","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}
Jihoon Kim, Mijung Choi, Jimin Lee, Inah Park, Kyungjin Kim, Han Kyoung Choe
The orbitofrontal cortex (OFC) plays a crucial role in mood disorders; however, its specific role in the emotional behaviors of mice remains unclear. This study investigates the bidirectional control of emotional behaviors using population calcium dynamics and optogenetic manipulation of OFC neurons. Fiber photometry of OFC neurons revealed that OFC excitatory neurons consistently responded to the onset and offset of aversive conditions, showing decreased activation in response to anxiogenic and stressful stimuli, including tail suspension, restraint stress, and exposure to the center of the open field. The selective activation of excitatory neurons in the OFC reduced the time spent in the center of the open field, whereas optogenetic activation of inhibitory neurons in the OFC induced the opposite behavioral changes. We also provided a brain-wide activation map for OFC excitatory and inhibitory neuron activation. Our findings demonstrate that excitatory and inhibitory neurons in the OFC play opposing roles in the regulation of emotional behaviors. These results provide new insights into the neural mechanisms underlying emotional control and suggest that targeting these specific neuronal populations may offer novel therapeutic strategies for emotional disorders.
{"title":"Bidirectional Control of Emotional Behaviors by Excitatory and Inhibitory Neurons in the Orbitofrontal Cortex.","authors":"Jihoon Kim, Mijung Choi, Jimin Lee, Inah Park, Kyungjin Kim, Han Kyoung Choe","doi":"10.5607/en24021","DOIUrl":"10.5607/en24021","url":null,"abstract":"<p><p>The orbitofrontal cortex (OFC) plays a crucial role in mood disorders; however, its specific role in the emotional behaviors of mice remains unclear. This study investigates the bidirectional control of emotional behaviors using population calcium dynamics and optogenetic manipulation of OFC neurons. Fiber photometry of OFC neurons revealed that OFC excitatory neurons consistently responded to the onset and offset of aversive conditions, showing decreased activation in response to anxiogenic and stressful stimuli, including tail suspension, restraint stress, and exposure to the center of the open field. The selective activation of excitatory neurons in the OFC reduced the time spent in the center of the open field, whereas optogenetic activation of inhibitory neurons in the OFC induced the opposite behavioral changes. We also provided a brain-wide activation map for OFC excitatory and inhibitory neuron activation. Our findings demonstrate that excitatory and inhibitory neurons in the OFC play opposing roles in the regulation of emotional behaviors. These results provide new insights into the neural mechanisms underlying emotional control and suggest that targeting these specific neuronal populations may offer novel therapeutic strategies for emotional disorders.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"33 5","pages":"225-237"},"PeriodicalIF":1.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681184","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}
Sushil Gaire, Haijie Yang, Manisha Dumre, Eun Jeong Lee, Sang-Myun Park, Eun-Hye Joe
In this study, we explored the impact of systemic inflammation on initial brain injury and repair processes, including neurite extension and synapse formation. For this purpose, we established a brain injury model by administering adenosine triphosphate (ATP), a component of damage-associated molecular patterns (DAMPs), through stereotaxic injection into the striatum of mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS-ip). Bulk RNA-sequencing (RNA-seq) analyses and immunostaining for microtubule-associated protein 2 (MAP2) and tyrosine hydroxylase (TH) showed that LPS-ip led to a reduction in initial brain injury, but inhibited neurite extension into the damaged brain. LPS-ip upregulated expression of defense response genes and anti-apoptotic genes, but decreased expression of genes associated with repair and regeneration. In addition, LPS-ip reduced levels of vGlut1 and PSD95 (markers for excitatory pre and post synapses, respectively), but had little effect on vGAT and gephyrin (markers for inhibitory pre and post synapses, respectively). Taken together, these findings suggest that systemic inflammation reduce initial damage but impede subsequent repair process.
{"title":"Systemic Inflammation Decreases Initial Brain Injury but Attenuates Neurite Extension and Synapse Formation during the Repair of Injured Brains.","authors":"Sushil Gaire, Haijie Yang, Manisha Dumre, Eun Jeong Lee, Sang-Myun Park, Eun-Hye Joe","doi":"10.5607/en24018","DOIUrl":"10.5607/en24018","url":null,"abstract":"<p><p>In this study, we explored the impact of systemic inflammation on initial brain injury and repair processes, including neurite extension and synapse formation. For this purpose, we established a brain injury model by administering adenosine triphosphate (ATP), a component of damage-associated molecular patterns (DAMPs), through stereotaxic injection into the striatum of mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS-ip). Bulk RNA-sequencing (RNA-seq) analyses and immunostaining for microtubule-associated protein 2 (MAP2) and tyrosine hydroxylase (TH) showed that LPS-ip led to a reduction in initial brain injury, but inhibited neurite extension into the damaged brain. LPS-ip upregulated expression of defense response genes and anti-apoptotic genes, but decreased expression of genes associated with repair and regeneration. In addition, LPS-ip reduced levels of vGlut1 and PSD95 (markers for excitatory pre and post synapses, respectively), but had little effect on vGAT and gephyrin (markers for inhibitory pre and post synapses, respectively). Taken together, these findings suggest that systemic inflammation reduce initial damage but impede subsequent repair process.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"33 5","pages":"251-262"},"PeriodicalIF":1.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681188","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}
Jinhyeong Joo,Ki Jung Kim,Jiwoon Lim,Sun Yeong Choi,Wuhyun Koh,C Justin Lee
Bestrophin-1 (BEST1) is a Ca2+-activated anion channel known for its role in astrocytes. Best1 is permeable to gliotransmitters, including GABA, to contribute to tonic GABA inhibition and modulate synaptic transmission in neighboring neurons. Despite the crucial functions of astrocytic BEST1, there is an absence of genetically engineered cell-type specific conditional mouse models addressing these roles. In this study, we developed an astrocyte-specific BEST1 conditional knock-out (BEST1 aKO) mouse line. Using the embryonic stem cell (ES cell) targeting method, we developed Best1 floxed mice (C57BL/6JCya-Best1em1flox/Cya), which have exon 3, 4, 5, and 6 of Best1 flanked by two loxP sites. By crossing with hGFAP-CreERT2 mice, we generated Best1 floxed/hGFAP-CreERT2 mice, which allowed for the tamoxifen-inducible deletion of Best1 under the human GFAP promoter. We characterized its features across various brain regions, including the striatum, hippocampal dentate gyrus (HpDG), and Parafascicular thalamic nucleus (Pf). Compared to the Cre-negative control, we observed significantly reduced BEST1 protein expression in immunohistochemistry (IHC) and tonic GABA inhibition in patch clamp recordings. The reduction in tonic GABA inhibition was 66.7% in the striatum, 46.4% in the HpDG, and 49.6% in the Pf. Our findings demonstrate that the BEST1 channel in astrocytes significantly contributes to tonic inhibition in the local brain areas. These mice will be valuable for future studies not only on tonic GABA release but also on tonic release of gliotransmitters mediated by astrocytic BEST1.
{"title":"Generation of Astrocyte-specific BEST1 Conditional Knockout Mouse with Reduced Tonic GABA Inhibition in the Brain.","authors":"Jinhyeong Joo,Ki Jung Kim,Jiwoon Lim,Sun Yeong Choi,Wuhyun Koh,C Justin Lee","doi":"10.5607/en24019","DOIUrl":"https://doi.org/10.5607/en24019","url":null,"abstract":"Bestrophin-1 (BEST1) is a Ca2+-activated anion channel known for its role in astrocytes. Best1 is permeable to gliotransmitters, including GABA, to contribute to tonic GABA inhibition and modulate synaptic transmission in neighboring neurons. Despite the crucial functions of astrocytic BEST1, there is an absence of genetically engineered cell-type specific conditional mouse models addressing these roles. In this study, we developed an astrocyte-specific BEST1 conditional knock-out (BEST1 aKO) mouse line. Using the embryonic stem cell (ES cell) targeting method, we developed Best1 floxed mice (C57BL/6JCya-Best1em1flox/Cya), which have exon 3, 4, 5, and 6 of Best1 flanked by two loxP sites. By crossing with hGFAP-CreERT2 mice, we generated Best1 floxed/hGFAP-CreERT2 mice, which allowed for the tamoxifen-inducible deletion of Best1 under the human GFAP promoter. We characterized its features across various brain regions, including the striatum, hippocampal dentate gyrus (HpDG), and Parafascicular thalamic nucleus (Pf). Compared to the Cre-negative control, we observed significantly reduced BEST1 protein expression in immunohistochemistry (IHC) and tonic GABA inhibition in patch clamp recordings. The reduction in tonic GABA inhibition was 66.7% in the striatum, 46.4% in the HpDG, and 49.6% in the Pf. Our findings demonstrate that the BEST1 channel in astrocytes significantly contributes to tonic inhibition in the local brain areas. These mice will be valuable for future studies not only on tonic GABA release but also on tonic release of gliotransmitters mediated by astrocytic BEST1.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"14 1","pages":"180-192"},"PeriodicalIF":2.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Numerous systemic diseases manifest with oral symptoms and signs. The molecular diagnosis of Alzheimer's disease (AD), the most prevalent neurodegenerative disease worldwide, currently relies on invasive or expensive methods, emphasizing the imperative for easily accessible biomarkers. In this study, we explored the expression patterns of key proteins implicated in AD pathophysiology within the taste buds of mice. We detected the expression of amyloid precursor protein (APP) and tau protein in the taste buds of normal C57BL/6 mice. Phosphorylated tau was predominantly found in type II and III taste cells, while APP was located in type I taste cells. Remarkably, we observed significantly stronger immunoreactivity to phosphorylated tau in the taste buds of aged AD mouse models compared to age-matched controls. These findings underscore the oral expression of biomarkers associated with AD, highlighting the diagnostic potential of the oral cavity for neurodegenerative diseases.
许多全身性疾病都有口腔症状和体征。阿尔茨海默病(AD)是全球最常见的神经退行性疾病,其分子诊断目前依赖于侵入性或昂贵的方法,这强调了寻找易于获取的生物标志物的必要性。在这项研究中,我们探索了与 AD 病理生理学有关的关键蛋白在小鼠味蕾中的表达模式。我们检测了正常 C57BL/6 小鼠味蕾中淀粉样前体蛋白(APP)和 tau 蛋白的表达。磷酸化 tau 主要存在于 II 型和 III 型味觉细胞中,而 APP 则存在于 I 型味觉细胞中。值得注意的是,与年龄匹配的对照组相比,我们在老年 AD 模型小鼠的味蕾中观察到了明显更强的磷酸化 tau 免疫反应。这些发现强调了口腔中与AD相关的生物标记物的表达,凸显了口腔对神经退行性疾病的诊断潜力。
{"title":"Phosphorylated Tau in the Taste Buds of Alzheimer's Disease Mouse Models.","authors":"Hyun Ji Kim,Bo Hye Kim,Dong Kyu Kim,Hanbin Kim,Sang-Hyun Choi,Dong-Hoon Kim,Myunghwan Choi,Inhee Mook-Jung,Yong Taek Jeong,Obin Kwon","doi":"10.5607/en24004","DOIUrl":"https://doi.org/10.5607/en24004","url":null,"abstract":"Numerous systemic diseases manifest with oral symptoms and signs. The molecular diagnosis of Alzheimer's disease (AD), the most prevalent neurodegenerative disease worldwide, currently relies on invasive or expensive methods, emphasizing the imperative for easily accessible biomarkers. In this study, we explored the expression patterns of key proteins implicated in AD pathophysiology within the taste buds of mice. We detected the expression of amyloid precursor protein (APP) and tau protein in the taste buds of normal C57BL/6 mice. Phosphorylated tau was predominantly found in type II and III taste cells, while APP was located in type I taste cells. Remarkably, we observed significantly stronger immunoreactivity to phosphorylated tau in the taste buds of aged AD mouse models compared to age-matched controls. These findings underscore the oral expression of biomarkers associated with AD, highlighting the diagnostic potential of the oral cavity for neurodegenerative diseases.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"65 1","pages":"202-214"},"PeriodicalIF":2.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sumi Park, Anu Shahapal, Sangjin Yoo, Hoyun Kwak, Minhyeok Lee, Sang-Myeong Lee, Jong-Ik Hwang, Jae Young Seong
FAM19A5, a novel secretory protein highly expressed in the brain, is potentially associated with the progression of Alzheimer's disease (AD). However, its role in the AD pathogenesis remains unclear. Here, we investigated the potential function of FAM19A5 in the context of AD. We generated APP/PS1 mice with partial FAM19A5 deficiency, termed APP/PS1/FAM19A5+/LacZ mice. Compared with control APP/PS1 mice, APP/PS1/FAM19A5+/LacZ mice exhibited significantly lower Aβ plaque density and prolonged the lifespan of the APP/PS1 mice. To further explore the therapeutic potential of targeting FAM19A5, we developed a FAM19A5 antibody. Administration of this antibody to APP/PS1 mice significantly improved their performance in the Y-maze and passive avoidance tests, indicating enhanced cognitive function. This effect was replicated in 5XFAD mice, a model of early-onset AD characterized by rapid Aβ accumulation. Additionally, FAM19A5 antibody treatment in 5XFAD mice led to enhanced exploration of novel objects and increased spontaneous alternation behavior in the novel object recognition and Y-maze tests, respectively, indicating improved cognitive function. These findings suggest that FAM19A5 plays a significant role in AD pathology and that targeting with FAM19A5 antibodies may be a promising therapeutic strategy for AD.
{"title":"FAM19A5 Deficiency Mitigates the Aβ Plaque Burden and Improves Cognition in Mouse Models of Alzheimer's Disease.","authors":"Sumi Park, Anu Shahapal, Sangjin Yoo, Hoyun Kwak, Minhyeok Lee, Sang-Myeong Lee, Jong-Ik Hwang, Jae Young Seong","doi":"10.5607/en24017","DOIUrl":"https://doi.org/10.5607/en24017","url":null,"abstract":"<p><p>FAM19A5, a novel secretory protein highly expressed in the brain, is potentially associated with the progression of Alzheimer's disease (AD). However, its role in the AD pathogenesis remains unclear. Here, we investigated the potential function of FAM19A5 in the context of AD. We generated APP/PS1 mice with partial FAM19A5 deficiency, termed APP/PS1/FAM19A5<sup>+/LacZ</sup> mice. Compared with control APP/PS1 mice, APP/PS1/FAM19A5<sup>+/LacZ</sup> mice exhibited significantly lower Aβ plaque density and prolonged the lifespan of the APP/PS1 mice. To further explore the therapeutic potential of targeting FAM19A5, we developed a FAM19A5 antibody. Administration of this antibody to APP/PS1 mice significantly improved their performance in the Y-maze and passive avoidance tests, indicating enhanced cognitive function. This effect was replicated in 5XFAD mice, a model of early-onset AD characterized by rapid Aβ accumulation. Additionally, FAM19A5 antibody treatment in 5XFAD mice led to enhanced exploration of novel objects and increased spontaneous alternation behavior in the novel object recognition and Y-maze tests, respectively, indicating improved cognitive function. These findings suggest that FAM19A5 plays a significant role in AD pathology and that targeting with FAM19A5 antibodies may be a promising therapeutic strategy for AD.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"33 4","pages":"193-201"},"PeriodicalIF":1.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282779","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}
Dong-Wook Kang,Sheu-Ran Choi,Hyunjin Shin,Hyeryeong Lee,Jaehong Park,Miae Lee,Miok Bae,Hyun-Woo Kim
Pain accompanied by depressive symptoms is a common reason for seeking medical assistance, and many chronic pain patients experience comorbid depression. The brain-derived neurotrophic factor (BDNF) is a well-known neurotrophin expressed throughout the nervous system, playing a crucial role in neuronal growth and neuroplasticity. This study aimed to examine the effects of exercise on BDNF expression in the nervous system and reserpine (RSP)-induced pain-depression dyad. RSP (1 mg/kg) was subcutaneously administered once daily for three days in mice. The exercise was performed using a rota-rod tester for seven consecutive days following RSP administration. Pain responses were evaluated using von Frey filaments, and depression-like behaviors were assessed through forced swimming and open field tests. Immunofluorescence staining was performed to examine the changes in BDNF expression in the dorsal root ganglion (DRG), spinal cord, and hippocampus. Administration of RSP reduced mechanical paw withdrawal threshold, increased immobility time in the forced swimming test, and decreased movement in the open field test. The immunoreactivity of BDNF was increased in the DRG and spinal dorsal regions, and decreased in the hippocampus after RSP administration. Physical exercise significantly reduced the RSP-induced mechanical hypersensitivity and depression-like behaviors. In addition, exercise suppressed not only the increased expression of BDNF in the DRG and spinal dorsal regions but also the decreased expression of BDNF in the hippocampus induced by RSP administration. These findings suggest that repetitive exercise could serve as an effective and non-invasive treatment option for individuals experiencing both pain and depression by modulating BDNF expression.
{"title":"Modulation of Brain-derived Neurotrophic Factor Expression by Physical Exercise in Reserpine-induced Pain-depression Dyad in Mice.","authors":"Dong-Wook Kang,Sheu-Ran Choi,Hyunjin Shin,Hyeryeong Lee,Jaehong Park,Miae Lee,Miok Bae,Hyun-Woo Kim","doi":"10.5607/en24014","DOIUrl":"https://doi.org/10.5607/en24014","url":null,"abstract":"Pain accompanied by depressive symptoms is a common reason for seeking medical assistance, and many chronic pain patients experience comorbid depression. The brain-derived neurotrophic factor (BDNF) is a well-known neurotrophin expressed throughout the nervous system, playing a crucial role in neuronal growth and neuroplasticity. This study aimed to examine the effects of exercise on BDNF expression in the nervous system and reserpine (RSP)-induced pain-depression dyad. RSP (1 mg/kg) was subcutaneously administered once daily for three days in mice. The exercise was performed using a rota-rod tester for seven consecutive days following RSP administration. Pain responses were evaluated using von Frey filaments, and depression-like behaviors were assessed through forced swimming and open field tests. Immunofluorescence staining was performed to examine the changes in BDNF expression in the dorsal root ganglion (DRG), spinal cord, and hippocampus. Administration of RSP reduced mechanical paw withdrawal threshold, increased immobility time in the forced swimming test, and decreased movement in the open field test. The immunoreactivity of BDNF was increased in the DRG and spinal dorsal regions, and decreased in the hippocampus after RSP administration. Physical exercise significantly reduced the RSP-induced mechanical hypersensitivity and depression-like behaviors. In addition, exercise suppressed not only the increased expression of BDNF in the DRG and spinal dorsal regions but also the decreased expression of BDNF in the hippocampus induced by RSP administration. These findings suggest that repetitive exercise could serve as an effective and non-invasive treatment option for individuals experiencing both pain and depression by modulating BDNF expression.","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"8 1","pages":"165-179"},"PeriodicalIF":2.4,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142248800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The harmful effects of blue light on the retina and health issues attributed to flickering light have been researched extensively. However, reports on the effects of flickering blue light at a frequency in the visible range on the retina are limited. This study aimed to non-invasively investigate the structural and functional changes in mice retinas following exposure to flickering blue light. BALB/c mice were subjected to non-flickering and flickering blue light, and changes in the retinal function and structure were assessed using electroretinography (ERG) and spectral-domain optical coherence tomography (SD-OCT), respectively. Retinal damage progression was monitored on days 3, 7, 14, and 42 following light exposure. Significant reductions in scotopic and photopic ERG responses were observed on day 3 (p<0.05). On day 7, the non-flickering and flickering groups demonstrated different functional changes: the flickering group showed further ERG response reduction, while the non-flickering group showed no reduction or slight improvement that was statistically insignificant (p>0.05). A similar trend lasted by day 14. On day 42, however, the difference between the non-flickering and flickering groups was significant, which was corroborated by the normalized amplitudes at 0, 0.5, and 1 log cd s/m2 (p<0.05). Quantitative and qualitative SD-OCT assays revealed more severe and progressive retinal damage in the flickering group throughout the study. Flickering blue light causes more persistent and severe retinal damage than non-flickering blue light and may be a risk factor for retinal degeneration even at frequencies as low as 20 Hz.
{"title":"Changes in Retinal Structure and Function in Mice Exposed to Flickering Blue Light: Electroretinographic and Optical Coherence Tomographic Analyses.","authors":"Yan Zhang, Sun-Sook Paik, In-Beom Kim","doi":"10.5607/en24011","DOIUrl":"10.5607/en24011","url":null,"abstract":"<p><p>The harmful effects of blue light on the retina and health issues attributed to flickering light have been researched extensively. However, reports on the effects of flickering blue light at a frequency in the visible range on the retina are limited. This study aimed to non-invasively investigate the structural and functional changes in mice retinas following exposure to flickering blue light. BALB/c mice were subjected to non-flickering and flickering blue light, and changes in the retinal function and structure were assessed using electroretinography (ERG) and spectral-domain optical coherence tomography (SD-OCT), respectively. Retinal damage progression was monitored on days 3, 7, 14, and 42 following light exposure. Significant reductions in scotopic and photopic ERG responses were observed on day 3 (p<0.05). On day 7, the non-flickering and flickering groups demonstrated different functional changes: the flickering group showed further ERG response reduction, while the non-flickering group showed no reduction or slight improvement that was statistically insignificant (p>0.05). A similar trend lasted by day 14. On day 42, however, the difference between the non-flickering and flickering groups was significant, which was corroborated by the normalized amplitudes at 0, 0.5, and 1 log cd s/m<sup>2</sup> (p<0.05). Quantitative and qualitative SD-OCT assays revealed more severe and progressive retinal damage in the flickering group throughout the study. Flickering blue light causes more persistent and severe retinal damage than non-flickering blue light and may be a risk factor for retinal degeneration even at frequencies as low as 20 Hz.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"33 3","pages":"152-164"},"PeriodicalIF":1.8,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590057","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}
Jea Kwon, Moonsun Sa, Hyewon Kim, Yejin Seong, C Justin Lee
Obesity is a growing health concern, mainly caused by poor dietary habits. Yet, accurately tracking the diet and food intake of individuals with obesity is challenging. Although 3D motion capture technology is becoming increasingly important in healthcare, its potential for detecting early signs of obesity has not been fully explored. In this research, we used a deep LSTM network trained with individual identity (identity-trained deep LSTM network) to analyze 3D time-series skeleton data from mouse models with diet-induced obesity. First, we analyzed the data from two different viewpoints: allocentric and egocentric. Second, we trained various deep recurrent networks (e.g., RNN, GRU, LSTM) to predict the identity. Lastly, we tested whether these models effectively encode obese-like motion representations by training a support vector classifier with the latent features from the last layer. Our experimental results indicate that the optimal performance is achieved when utilizing an identity-trained deep LSTM network in conjunction with an egocentric viewpoint. This approach suggests a new way to use deep learning to spot health risks in mouse models of obesity and should be useful for detecting early signs of obesity in humans.
{"title":"Egocentric 3D Skeleton Learning in a Deep Neural Network Encodes Obese-like Motion Representations.","authors":"Jea Kwon, Moonsun Sa, Hyewon Kim, Yejin Seong, C Justin Lee","doi":"10.5607/en24008","DOIUrl":"10.5607/en24008","url":null,"abstract":"<p><p>Obesity is a growing health concern, mainly caused by poor dietary habits. Yet, accurately tracking the diet and food intake of individuals with obesity is challenging. Although 3D motion capture technology is becoming increasingly important in healthcare, its potential for detecting early signs of obesity has not been fully explored. In this research, we used a deep LSTM network trained with individual identity (identity-trained deep LSTM network) to analyze 3D time-series skeleton data from mouse models with diet-induced obesity. First, we analyzed the data from two different viewpoints: allocentric and egocentric. Second, we trained various deep recurrent networks (e.g., RNN, GRU, LSTM) to predict the identity. Lastly, we tested whether these models effectively encode obese-like motion representations by training a support vector classifier with the latent features from the last layer. Our experimental results indicate that the optimal performance is achieved when utilizing an identity-trained deep LSTM network in conjunction with an egocentric viewpoint. This approach suggests a new way to use deep learning to spot health risks in mouse models of obesity and should be useful for detecting early signs of obesity in humans.</p>","PeriodicalId":12263,"journal":{"name":"Experimental Neurobiology","volume":"33 3","pages":"119-128"},"PeriodicalIF":1.8,"publicationDate":"2024-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11247279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590058","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}