Article
Neurosciences
Yi-Ting Cheng, Junsung Woo, Estefania Luna-Figueroa, Ehson Maleki, Akdes Serin Harmanci, Benjamin Deneen
Summary: Social experience plays a crucial role in the development and maintenance of higher-order brain function. By studying astrocyte function, this research shows that social isolation leads to increased Ca2+ activity and global changes in gene expression in hippocampal astrocytes of juvenile mice. The upregulation of the Ca2+ channel TRPA1 in astrocytes after social deprivation is found to be responsible for the physiological and cognitive deficits associated with social deprivation. Moreover, the inhibition of hippocampal circuits by TRPA1 is mediated by the release of the inhibitory neurotransmitter GABA by astrocytes after social deprivation.
Article
Neurosciences
Marcin Wyroslak, Grzegorz Dobrzanski, Jerzy W. Mozrzymas
Summary: In this study, we investigated the effect of NMDA-induced plasticity on tonic inhibition in somatostatin- and parvalbumin-containing interneurons. Our results showed that NMDA application enhanced tonic conductance in somatostatin-containing interneurons, while reducing tonic inhibition in both fast-spiking and non-fast-spiking parvalbumin-positive cells. These changes were associated with alterations in the content of α5 and δ-subunit-containing GABA(A) receptors.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Chloe M. Erikson, Kevin T. Douglas, Talia O. Thuet, Ben D. Richardson, Claudia Mohr, Hiroko Shiina, Josh S. Kaplan, David J. Rossi
Summary: Genetic differences in cerebellar sensitivity to alcohol influence alcohol consumption phenotype in animal models, with alcohol affecting GABA(A)R currents differently in different genotypes, influenced by nNOS expression levels.
Article
Biology
Vincent Robert, Ludivine Therreau, Vivien Chevaleyre, Eude Lepicard, Cecile Viollet, Julie Cognet, Arthur J. Y. Huang, Roman Boehringer, Denis Polygalov, Thomas J. McHugh, Rebecca Ann Piskorowski
Summary: The study reveals that the hypothalamic supramammillary nucleus (SuM) influences the hippocampal area CA2 through a mix of excitatory and inhibitory responses. The inhibitory effect of SuM input is mediated largely by parvalbumin-expressing basket cells, enhancing the precision of action potential firing in CA2 pyramidal neurons and modulating CA1 activity. Synchronized output from CA2 drives pulsed inhibition in CA1, laying the foundation for understanding how SuM activity contributes to social memory encoding in the local hippocampal circuit.
Article
Multidisciplinary Sciences
Yuya Sakimoto, Ako Shintani, Daiki Yoshiura, Makoto Goshima, Hiroyuki Kida, Dai Mitsushima
Summary: This study reports the postnatal development of hippocampal function and the impact of an inhibitory avoidance task on synaptic plasticity in rats. The results show an improvement in learning performance from juvenile to adulthood and different effects of training on synaptic amplitudes at different time points.
SCIENTIFIC REPORTS
(2022)
Article
Psychology, Biological
Yun Lu, Chang-jun Li, Wen-jing Li, Mei Zhou, Li Liu
Summary: This study found that the alteration of GABA(B1) and GABA(B2) subunits may be involved in depressive-like behaviors caused by chronic cerebral hypoperfusion.
PHYSIOLOGY & BEHAVIOR
(2022)
Article
Neurosciences
Marcin Wyroslak, Katarzyna Lebida, Jerzy W. Mozrzymas
Summary: The study examined the plasticity of tonic inhibition in hippocampal pyramidal neurons under NMDAR-dependent GABAergic inhibitory long-term potentiation (iLTP) induction protocol. It was found that alpha 5-containing GABA(A)Rs played a key role in mediating the plastic change in tonic current during this process.
Article
Neurosciences
R. G. K. Munn, A. Freeburn, D. P. Finn, H. C. Heller
Summary: Down Syndrome is a genetic condition caused by trisomy 21, leading to difficulties in learning and memory. The hippocampus has been found to play a key role in learning and memory, and recent research with mouse models of Down Syndrome has shown differences in hippocampal activity. Excess GABAergic innervation from the Medial Septum to the hippocampus is thought to be one of the main functional differences in Down Syndrome. In this study, the activity of region CA1 in the hippocampus was examined in Ts65Dn mice compared to their non-trisomic 2N littermates using in vivo electrophysiology. While the spatial properties of place cells in CA1 were normal in Ts65Dn mice, there were profound alterations in the phasic relationship of both CA1 place cells and gamma rhythms to theta rhythm. These findings suggest that the overall network state of the hippocampus is critically important for its function and provide further evidence for excess inhibitory control as the cause of hippocampal dysfunction in Down Syndrome.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Nadia Carolina Rodrigues, Armando Silva-Cruz, Ana Caulino-Rocha, Andreia Bento-Oliveira, Joaquim Alexandre Ribeiro, Diana Cunha-Reis
Summary: Long-term potentiation (LTP) is a cellular process studied extensively, with LTP induced by theta burst stimulation (TBS) in the hippocampal CA1 area depending on NMDA receptor and CaMKII activity, but not on PKA or PKC activity. Additionally, partial dependence on GABAB receptor activation and potentiation by GABAA receptor blockade and less by GAT-1 transporter blockade enhance LTP, while kinases like PKA, PKC, or ERK/MAPK family may not be essential for its expression in the hippocampal CA1 area.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Cell Biology
Min-Yi Wu, Wen-Jun Zou, Pei Yu, Yuhua Yang, Shao-Jian Li, Qiang Liu, Jiatian Xie, Si-Qi Chen, Wei-Jye Lin, Yamei Tang
Summary: Radiation therapy for head and neck tumors can result in cognitive impairments, which are related to abnormal hippocampal function. However, the long-term effects of radiation on the electrophysiological adaptation of hippocampal neurons are not well understood. This study found that mice exhibited cognitive impairment three months after cranial irradiation, and there was a reduction in spike firing and excitatory synaptic input, as well as an increase in inhibitory inputs in hippocampal CA1 pyramidal neurons. These changes were associated with altered expression of synaptic plasticity markers. Overall, radiation can impair intrinsic excitability and synaptic plasticity in hippocampal neurons.
NEURAL REGENERATION RESEARCH
(2022)
Article
Anesthesiology
Marc A. Manzo, Dian-Shi Wang, Winston W. Li, Arsene Pinguelo, Mariana O. Popa, Shahin Khodaei, John R. Atack, Ruth A. Ross, Beverley A. Orser
Summary: The study investigated the effects of five alpha 5-NAMs on tonic current in mouse hippocampal neurones. Results showed a concentration-dependent decrease in tonic current, with variations in potencies among the compounds. The study suggests that studying the effects of alpha 5 GABA(A) receptor-selective drugs on the tonic inhibitory current in neurones could inform the selection of compounds for future clinical trials.
BRITISH JOURNAL OF ANAESTHESIA
(2021)
Article
Medical Laboratory Technology
Dan Wu, Yang Yang, Chuanxin Duan
Summary: CDC42 and IL-4 levels are elevated in patients with otitis media with effusion (OME), and they are intercorrelated and positively associated with effusion viscosity and hearing loss degree.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2022)
Article
Neurosciences
Wuhyun Koh, Mijeong Park, Ye Eun Chun, Jaekwang Lee, Hyun Soo Shim, Mingu Gordon Park, Sunpil Kim, Moonsun Sa, Jinhyeong Joo, Hyunji Kang, Soo-Jin Oh, Junsung Woo, Heejung Chun, Seung Eun Lee, Jinpyo Hong, Jiesi Feng, Yulong Li, Hoon Ryu, Jeiwon Cho, C. Justin Lee
Summary: This study found that hippocampal astrocytes regulate NMDAR tone by releasing D-serine and glutamate, with the process mediated by BEST1. Decreased NMDAR tone results in impaired cognitive flexibility, and NMDAR tone during initial learning is crucial for subsequent learning.
BIOLOGICAL PSYCHIATRY
(2022)
Article
Neurosciences
Ekin Su Akdemir, Junsung Woo, Navish A. Bosquez Huerta, Brittney Lozzi, Andrew K. Groves, Akdes Serin Harmanci, Benjamin Deneen
Summary: Astrocytes, the most abundant glial cell in the brain, perform various tasks to support neuronal function and circuit activities. Through the study of astrocytes, a unique subpopulation called Lfng-GFP(+) astrocytes was identified, which occupies a distinct anatomic location in the spinal cord and directly contributes to neuronal function and sensory responses.
JOURNAL OF NEUROSCIENCE
(2022)
Review
Clinical Neurology
Yi-Ting Cheng, Junsung Woo, Benjamin Deneen
Summary: This review focuses on the emerging areas in astrocyte biology, including region-specific circuit regulation, molecular diversity, and transcriptional regulation. By exploring how molecular diversity is converted to functional diversity of astrocytes, we gain a nascent understanding of how transcriptional mechanisms regulate this process.
Article
Clinical Neurology
Thuy Linh Pham, Chan Noh, Chiranjivi Neupane, Ramesh Sharma, Hyun Jin Shin, Ki Duk Park, C. Justin Lee, Hyun-Woo Kim, So Yeong Lee, Jin Bong Park
Summary: The study demonstrates that KDS, a reversible MAO-B inhibitor, can alleviate neuropathic pain through regulating excitatory transmission and neuroinflammation. KDS may represent a promising direction for future pain medicine.
Article
Medicine, Research & Experimental
Moonsun Sa, Jung Moo Lee, Mingu Gordon Park, Jiwoon Lim, Jong Min Joseph Kim, Wuhyun Koh, Bo-Eun Yoon, C. Justin Lee
Summary: This study found that chronic high-fat diet leads to increased reactivity and GABA-synthesizing enzyme expression in astrocytes of the hypothalamus in obese mice, however, tonic inhibition of GABA remains unaltered, which is due to GABA clearance by neuronal GAT1. These results suggest that GABA-related pathways in the hypothalamic ARC play a dynamic role in maintaining tonic inhibition.
EXPERIMENTAL NEUROBIOLOGY
(2022)
Article
Medicine, Research & Experimental
Jung Moo Lee, Moonsun Sa, Heeyoung An, Jong Min Joseph Kim, Jea Kwon, Bo-Eun Yoon, C. Justin Lee
Summary: In this study, an astrocyte-specific MAOB conditional knockout mouse was generated, and it was found that astrocytic MAOB is a critical enzyme for the synthesis of GABA in astrocytes.
EXPERIMENTAL NEUROBIOLOGY
(2022)
Article
Microbiology
Tai Young Kim, Sangeun Jeon, Meehyun Ko, Young Eun Du, So-Ri Son, Dae Sik Jang, Seungtaek Kim, C. Justin Lee
Summary: The study found that Codonopsis lanceolate extract and its active compound lancemaside A have potent inhibitory activity against SARS-CoV-2 infection. The inhibitory effect is achieved by altering membrane cholesterol and blocking membrane fusion between the virus and host cells. Furthermore, lancemaside A can also block the entry pathways of different SARS-CoV-2 variants and prevent the formation of multinucleated syncytia caused by viral spike protein-mediated membrane fusion.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Biochemistry & Molecular Biology
Dong-Chan Seo, Yeon Ha Ju, Jin-Ju Seo, Soo-Jin Oh, C. Justin Lee, Seung Eun Lee, Min-Ho Nam
Summary: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms. In a PD model, activating dopamine-decarboxylase positive neurons significantly improved motor symptoms and restored dopamine synthesis enzyme expression. This suggests that dormant dopaminergic neurons could be a potential therapeutic strategy for PD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Mingu Gordon Park, Suyeon Yellena Kim, C. Justin Lee
Summary: Ornithine decarboxylase (ODC), a key enzyme in polyamine synthesis, is a therapeutic target for cancer and Alzheimer's disease (AD). We report a DMSO-tolerant ODC assay that overcomes the limitations of dimethyl sulfoxide (DMSO) in high-throughput screening (HTS). Furthermore, we optimized ODC production in human cell lines for HTS. Our newly developed assay represents a crucial first step in discovering more effective ODC modulators.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Biology
Anna Shin, Jia Ryoo, Kwanhoo Shin, Junesu Lee, Seohui Bae, Dae-Gun Kim, Sae-Geun Park, Daesoo Kim
Summary: This study demonstrates that a circuit from CamKII alpha-positive neurons of the medial preoptic area to the ventral periaqueductal gray facilitates exploration and fear extinction in mice. The findings provide insights into the mechanism of exposure therapy and its potential application in treating panic and post-traumatic stress disorder patients.
COMMUNICATIONS BIOLOGY
(2023)
Article
Clinical Neurology
Min-Ho Nam, Hae Young Ko, Dongwoo Kim, Sangwon Lee, Yongmin Mason Park, Seung Jae Hyeon, Woojin Won, Jee-In Chung, Seon Yoo Kim, Han Hee Jo, Kyeong Taek Oh, Young-Eun Han, Gwan-Ho Lee, Yeon Ha Ju, Hyowon Lee, Hyunjin Kim, Jaejun Heo, Mridula Bhalla, Ki Jung Kim, Jea Kwon, Thor D. Stein, Mingyu Kong, Hyunbeom Lee, Seung Eun Lee, Soo-Jin Oh, Joong-Hyun Chun, Mi-Ae Park, Ki Duk Park, Hoon Ryu, Mijin Yun, C. Justin Lee
Summary: This study discovered that PET imaging with C-11-acetate and F-18-fluorodeoxyglucose (F-18-FDG) can functionally visualize the reactive astrocyte-mediated neuronal hypometabolism in brains with neuroinflammation and AD. The alterations of acetate and glucose metabolism in diseased brains and their impact on AD pathology were investigated using various approaches. The findings suggest the potential value of PET imaging with C-11-acetate and F-18-FDG in visualizing reactive astrogliosis and associated neuronal glucose hypometabolism for AD patients.
Article
Medicine, Research & Experimental
Abdelrahman M. Alkahwaji, Hee-Sup Shin, Justin Lee
Summary: Developing social strategies for equal resource sharing and maximizing long-term benefits of conflict resolution is crucial for appropriate social interactions. Hunger, as a physical need, plays a dominant role in social decision-making, but its effects are not well understood.
EXPERIMENTAL NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kwang Wook Min, Namsuk Kim, Jae Hoon Lee, Younghoon Sung, Museong Kim, Eun Jung Lee, Jong-Myeong Kim, Jae-Hyun Kim, Jaeyoung Lee, Wonjin Cho, Jee Myung Yang, Nury Kim, Jaehoon Kim, C. Justin Lee, Young-Gyun Park, Seung-Hee Lee, Han-Woong Lee, Jin Woo Kim
Summary: The protein Vax1 is crucial for the development of binocular vision, as it regulates the growth of optic nerves and the formation of the optic chiasm. A mutant Vax1 was found to impair the optic nerve growth and connectivity, leading to impaired depth perception and low vision. This study highlights the importance of Vax1 in visual development.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Woojin Won, Hyun-Ji Choi, Ji-Young Yoo, Daeun Kim, Tai Young Kim, YeonHa Ju, Ki Duk Park, Hyunbeom Lee, Sang Youn Jung, C. Justin Lee
Summary: The study reveals that MAO-B is closely associated with joint inflammation and cognitive impairment in RA patients, suggesting its potential as a therapeutic target. Inhibiting MAO-B with a newly developed reversible inhibitor also showed promising results in ameliorating joint inflammation and cognitive impairment in mouse models of RA.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Moonsun Sa, Mingu Gordon Park, C. Justin Lee
Summary: Recent research has found that reactive astrocytes in the hypothalamus play a significant role in diet-induced obesity, as they release the major inhibitory transmitter GABA to directly influence nearby neurons involved in energy expenditure. These findings shed light on the interaction between reactive astrocytes and neighboring neurons, providing new potential therapeutic targets for obesity.
MOLECULES AND CELLS
(2022)