Article
Biochemistry & Molecular Biology
Liying Chen, Yingwei Xu, Heming Cheng, Zhongxia Li, Nanxi Lai, Menghan Li, Yeping Ruan, Yang Zheng, Fan Fei, Cenglin Xu, Jiao Ma, Shuang Wang, Yan Gu, Feng Han, Zhong Chen, Yi Wang
Summary: This study found that adult-born dentate granule cells (abDGCs) born at a critical period after epileptogenic insult can influence the duration of seizures. Activation or inhibition of these cells can significantly extend or curtail seizure duration, providing new insights for precise treatment of epilepsy.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Behavioral Sciences
Govert Hoogland, Marjolein Raijmakers, Elke Clynen, Bert Brone, Jean-Michel Rigo, Ann Swijsen
Summary: Prolonged febrile seizures (FS) are a risk factor for temporal lobe epilepsy. The dentate gyrus, a region where neurogenesis continues postnatally, shows increased survival rate and structural integration of newborn dentate granule cells (DGCs) after experimental FS. These mature post-FS born DGCs also exhibit altered receptor expression. This study aimed to investigate if these molecular and structural changes are accompanied by altered cellular functioning.
BRAIN AND BEHAVIOR
(2022)
Article
Multidisciplinary Sciences
Brenna Hourigan, Spencer D. Balay, Graydon Yee, Saloni Sharma, Qiumin Tan
Summary: New neurons continuously arise in the adult hippocampus, but little is known about the factors regulating neuronal differentiation, migration, and dendrite maturation. Our study reveals a previously unrecognized role of the transcriptional repressor protein CIC in adult hippocampal neurogenesis, as its loss impedes neuronal lineage development and disrupts dendritic arborization and migration of adult-born neurons.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Dong Sun, Leena Milibari, Jin-Xiu Pan, Xiao Ren, Ling-Ling Yao, Yang Zhao, Chen Shen, Wen-Bing Chen, Fu-Lei Tang, Daehoon Lee, Jun-Shi Zhang, Lin Mei, Wen-Cheng Xiong
Summary: The research identified the critical functions of Ocn-Cre(+) dDG neurons in suppressing anxiety-like behaviors and promoting adult DG neurogenesis, likely through the activation of BDNF.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Biology
Nicholas P. Vyleta, Jason S. Snyder
Summary: Adult-born granule neurons in the hippocampus exhibit enhanced excitability and plasticity during immature stages, which is believed to contribute to their unique roles in learning and memory. Our findings reveal hyper-excitability in the presynaptic terminals of mossy fibers onto CA3 pyramidal neurons, and suggest rapid functionality in immature neurons. Electrophysiological recordings in mouse hippocampal slices demonstrate faster maturation of action potential waveforms in the presynaptic bouton of adult-born granule neurons compared to the soma.
COMMUNICATIONS BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Gabriel Berdugo-Vega, Shonali Dhingra, Federico Calegari
Summary: This article reviews a wealth of research in cellular, anatomical, behavioral, and computational studies on the mammalian hippocampus, aiming to understand the fundamental mechanisms underlying cognition. Despite accumulating knowledge on how the hippocampus processes and stores information for learning and memory, our understanding of hippocampal cognitive function remains incomplete. The article discusses the structural separability of the two blades of the dentate gyrus in the hippocampus and proposes a model that suggests differences in connectivity and adult neurogenesis in the two blades may contribute to subtly different cognitive functions.
Article
Neurosciences
Sang-Yoon Kim, Woochang Lim
Summary: Young immature granule cells (imGCs) appear in the hippocampal dentate gyrus through adult neurogenesis. These imGCs exhibit two competing properties: high excitability and low excitatory innervation.
COGNITIVE NEURODYNAMICS
(2023)
Article
Neurosciences
Jiao Ma, Zhechun Hu, Huimin Yue, Yujian Luo, Chao Wang, Xuan Wu, Yan Gu, Lang Wang
Summary: In this study, the researchers found that the metabotropic glutamate receptor 2 (GRM2) is highly expressed in hippocampal dentate granule cells (DGCs) and plays a crucial role in regulating their development and functional integration. Lack of GRM2 leads to developmental defects and impaired cognitive functions in the hippocampus. Interestingly, knocking down GRM2 resulted in the excessive activation of the MEK/ERK1/2 pathway, which was ameliorated by inhibiting MEK.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Cell & Tissue Engineering
Ya-Dong Li, Yan-Jia Luo, Ling Xie, Dalton S. Tart, Ryan N. Sheehy, Libo Zhang, Leon G. Coleman, Xian Chen, Juan Song
Summary: Patients with Alzheimer's disease (AD) show memory loss, depression, and anxiety, along with impaired adult hippocampal neurogenesis (AHN). This study demonstrates that optogenetic stimulation of the hypothalamic supramammillary nucleus (SuM) enhances AHN in AD mouse models, improving memory and emotion deficits. Activation of SuM-enhanced adult-born neurons (ABNs) triggers synaptic plasticity and microglia phagocytosis, providing insights into the signaling mechanisms involved.
Review
Neurosciences
Gaifen Li, Jia Liu, Yuying Guan, Xunming Ji
Summary: Hypoxia plays a crucial role in regulating various cell functions, including stem cells and neural stem cells. Hypoxia stimulation in specific brain regions can promote proliferation, migration, and maturation of neural stem cells, potentially offering a promising strategy for treating central nervous system diseases.
CNS NEUROSCIENCE & THERAPEUTICS
(2021)
Article
Neurosciences
Muhammad N. Arshad, Alejandro Pinto, Henriette van Praag, Janice R. Naegele
Summary: Adult neurogenesis in the rodent hippocampus is affected by seizures and can lead to hyperexcitable circuits. Transplantation of GABAergic interneurons from the medial ganglionic eminence (MGE) into the dentate gyrus (DG) of mice with temporal lobe epilepsy (TLE) can reduce seizures and form inhibitory connections with adult-born granule cells (GCs). This study found that TLE increased excitatory inputs onto adult-born GCs, but mice with MGE grafts showed reduced excitatory inputs and increased GABAergic interneuron innervation of GCs, suggesting that MGE grafts can prevent epilepsy-associated changes in adult-born GC connectivity.
PROGRESS IN NEUROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Simona Gribaudo, Daniele Saraulli, Giulia Nato, Sara Bonzano, Giovanna Gambarotta, Federico Luzzati, Marco Costanzi, Paolo Peretto, Serena Bovetti, Silvia De Marchis
Summary: Neurogranin plays a crucial role in modulating neuronal signaling and is involved in synaptic plasticity and cognitive functions. Its expression in adult-born GCs is associated with their mature state and active phosphorylation at post-synaptic sites. Defective spine density and impaired odor-reward associative memory are observed in Ng knockout mice, suggesting a role for Ng in GC plasticity and olfactory associative memory formation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Xinli Xu, Rui O. Beleza, Francisco Q. Goncalves, Sergio Valbuena, Sofia Alcada-Morais, Nelio Goncalves, Joana Magalhaes, Joao M. M. Rocha, Sofia Ferreira, Ana S. G. Figueira, Juan Lerma, Rodrigo A. Cunha, Ricardo J. Rodrigues, Joana M. Marques
Summary: This study reveals that adenosine A(2A) receptors (A(2A)R) contribute to circuit remodeling in the mature brain, specifically in the hippocampal mossy fiber (MF) sprouting found in diseases like temporal lobe epilepsy. A(2A)R activation in dentate granule cells induces the formation of abnormal secondary axons, which is activated by extracellular ATP-derived adenosine. These findings highlight the role of the CD73-A(2A)R axis in regulating circuit remodeling in the mature brain.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Nicholas P. Vyleta, Jason S. Snyder
Summary: Studies suggest that adult-born neurons display slow development of LTP at LPP synapses, but gradually increase over a period of 3-4 months, indicating a presynaptic mechanism. This new form of neuron plasticity may be relevant for maintaining cognitive function in aging.
Review
Cell Biology
Jennifer Leifeld, Eckart Foerster, Gebhard Reiss, Mohammad I. K. Hamad
Summary: The extracellular matrix (ECM) of the nervous system is a dynamically adaptable compartment between neuronal cells, participating in physiological functions. It is composed of carbohydrates and proteins secreted by different cell types. ECM molecules play important roles in development, synaptic plasticity, neurodegeneration, and regeneration processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ying Wan, Xuedong Li, Elise Slevin, Kelly Harrison, Tian Li, Yudian Zhang, James E. Klaunig, Chaodong Wu, Ashok K. Shetty, X. Charlie Dong, Fanyin Meng
Summary: Aging leads to changes in the structure and functions of hepatic cells, including LSECs, which play a significant role in liver homeostasis. As LSECs age, they experience reduced fenestrations, increased oxidative stress, and decreased nitric oxide availability, contributing to hepatic inflammation and fibrosis. Understanding the role of LSECs in the early detection and intervention of liver fibrosis is crucial.
Review
Cell Biology
Leelavathi N. Madhu, Maheedhar Kodali, Ashok K. Shetty
Summary: The expanded lifespan of people has led to an increase in age-related disorders, but the drug metformin shows promise in alleviating age-related cognitive dysfunction, although its efficacy in the nondiabetic population is still unclear.
NEURAL REGENERATION RESEARCH
(2022)
Article
Cell Biology
Leelavathi N. Madhu, Yogish Somayaji, Ashok K. Shetty
Summary: Regular physical exercise can prevent aging and Alzheimer's disease and improve cognitive function. Drugs or biologics that mimic the benefits of exercise, such as irisin, have shown promise in improving cognitive impairments. Irisin acts on neural cells and modulates neuroinflammatory cascades to simulate the cognitive benefits of exercise.
AGEING RESEARCH REVIEWS
(2022)
Editorial Material
Cell Biology
Zhuang-Yao D. Wei, Ashok K. Shetty
Summary: This article discusses a recent study that suggests using a miRNA triad, consisting of miR-181a-5p, miR-146a-5p, and miR-148a-3p, for diagnosing ACI, MCI, and AD. The study explores the impact of elevated levels of this miRNA triad on neural plasticity and cognitive function in the brain and the potential of inhibiting it to improve cognitive function in MCI and AD.
Review
Cell & Tissue Engineering
K. R. Sabitha, Divya Chandran, Ashok K. Shetty, Dinesh Upadhya
Summary: This review summarizes the information obtained from patient-derived iPSCs on neurodevelopmental and neuropathological defects in lysosomal storage diseases. It reveals various cellular and molecular defects and discusses therapeutic applications such as drug discovery and gene therapy for LSDs.
STEM CELLS AND DEVELOPMENT
(2022)
Article
Neurosciences
Raghavendra Upadhya, Leelavathi N. Madhu, Shama Rao, Ashok K. Shetty
Summary: This study demonstrates the ability of EVs derived from hiPSC-induced neural stem cells to modulate activated human microglia and reduce inflammation. The presence of the protein PTX3 and miRNA miR-21-5p in hNSC-EVs is essential for their anti-inflammatory effects. These findings suggest the potential of hNSC-EVs as a therapeutic strategy for neuroinflammatory diseases.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Immunology
Sahithi Attaluri, Raghavendra Upadhya, Maheedhar Kodali, Leelavathi N. Madhu, Dinesh Upadhya, Bing Shuai, Ashok K. Shetty
Summary: Persistent cognitive impairment is a common symptom in veterans with chronic Gulf War Illness (GWI) and is associated with neuroinflammation. This study found that cognitive dysfunction in chronic GWI is related to astrocyte hypertrophy, activated microglia, and increased proinflammatory cytokine levels. The study also discovered altered LT signaling in the brain, which may contribute to chronic neuroinflammation in GWI.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Neurosciences
Maria Eduarda T. Oliveira, Gustavo V. B. Paulino, Erivaldo D. dos Santos Junior, Francisca A. da Silva Oliveira, Vania M. M. Melo, Jeferson S. Ursulino, Thiago M. de Aquino, Ashok K. Shetty, Melissa Fontes Landell, Daniel Leite Goes Gitai
Summary: This study evaluated the changes in gut microbiota composition and fecal metabolomic profile in epileptic rats. The results showed significant alterations in gut microbiota and fecal metabolites in epileptic rats, indicating a potential correlation between dysbacteriosis and epileptic brain activity. The findings suggest that targeting the gut microbiota could be a novel approach for preventing and treating acquired epilepsy.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Cell & Tissue Engineering
Dinesh Upadhya, Sahithi Attaluri, Yan Liu, Bharathi Hattiangady, Olagide W. Castro, Bing Shuai, Yi Dong, Su-Chun Zhang, Ashok K. Shetty
Summary: The study found that transplanted interneurons can directly regulate spontaneous recurrent seizures (SRS) and specific cognitive functions in a rat model of chronic temporal lobe epilepsy (TLE).
NPJ REGENERATIVE MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Ying Wan, Tianhao Zhou, Elise Slevin, Sachiko Koyama, Xuedong Li, Kelly Harrison, Tian Li, Bingru Zhou, Sugeily Ramos Lorenzo, Yudian Zhang, Wenjuan Xu, James E. Klaunig, Chaodong Wu, Ashok K. Shetty, Chiung-Kuei Huang, Fanyin Meng
Summary: Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by cholestasis, inflammation, and fibrotic scar formation. This study investigated the role of liver-specific microRNA-34a in ductular reaction and liver fibrosis. They found that miR-34a expression was increased in PSC livers, and its knockout in a cholestatic liver disease model reduced ductular pathology and fibrotic responses.
Editorial Material
Neurosciences
Kellysson Bruno Oliveira, Igor Santana de Melo, Bianca Rodrigues Melo da Silva, Keylla Lavinia da Silva Oliveira, Robinson Sabino-Silva, Lucas Anhezini, Pedro Lourenco Katayama, Victor Rodrigues Santos, Ashok K. Shetty, Olagide Wagner de Castro
Summary: Hypertension is a critical risk factor for COVID-19 as SARS-CoV-2 invasion affects the cardiovascular system and alters blood pressure regulation. The invasion of carotid and aortic baroreceptors by the virus leads to infection of NTS and PVN, causing blood pressure alterations. Additionally, the virus may disrupt the renin-angiotensin-aldosterone system and increase sympathetic activity, resulting in hypertension and contributing to cardiovascular complications.
NEUROSCIENCE INSIGHTS
(2023)
Review
Neurosciences
Maheedhar Kodali, Tanvi Jankay, Ashok K. Shetty, Doodipala Samba Reddy
Summary: This article discusses the pathophysiology and potential treatments for Gulf War Illness (GWI), a chronic neuropsychiatric illness linked to chemical exposures during the first Gulf War. Despite the lack of effective treatments, there are numerous current therapeutic interventions being investigated in preclinical models of GWI. Promising therapies include curcumin, resveratrol, and ketamine, which are currently undergoing clinical trials in GWI veterans. Neurosteroids also show potential as a medicine for GWI due to their neuroprotective properties. Urgent clinical studies are needed to evaluate and launch an effective therapy for veterans with GWI.
PSYCHOPHARMACOLOGY
(2023)
Review
Cell & Tissue Engineering
Catherine Hering, Ashok K. Shetty
Summary: This review discusses the therapeutic efficacy of extracellular vesicles (EVs) derived from neural stem cells (NSC-EVs), astrocytes (ADEVs), and microglia (MDEVs) in traumatic brain injury (TBI) models. NSC-EV or ADEV therapy has been shown to mediate neuroprotective effects and improve motor and cognitive function after TBI. However, the therapeutic effects of naive MDEVs are yet to be tested rigorously in TBI models.
STEM CELLS TRANSLATIONAL MEDICINE
(2023)
Article
Materials Science, Biomaterials
Claudia A. Collier, Steven Foncerrada, Abigail J. Clevenger, Ashok Shetty, Shreya A. Raghavan
Summary: Gulf War Illness (GWI), resulting from chemical exposure during the Gulf War, affects gastrointestinal motility. This study examines the hypothesis that exposure to pyridostigmine bromide (PB) leads to severe enteric neuro-inflammation and disruptions in colonic motility. Experiments conducted on male mice show reduced colonic forces, increased inflammation, and decreased numbers of enteric neurons responsible for mediating colonic motility in GWI. These findings contribute to a better understanding of the mechanisms underlying GWI and can potentially lead to improved therapeutic options for affected individuals.
Review
Geriatrics & Gerontology
Zhuang-Yao D. Wei, Ketty Liang, Ashok K. Shetty
Summary: SARS-CoV-2 uses a spike protein to enter human cells by binding to ACE-2, resulting in COVID-19. COVID-19 primarily causes respiratory infection and can lead to severe systemic inflammation. Neurological symptoms are also common in some patients.