Researches:

Article title: SARS-CoV-2 spike protein induces cognitive deficit and anxiety-like behavior in mouse via non-cell autonomous hippocampal neuronal death
Authors: Junyoung Oh, Woo-Hyun Cho, Ellane Barcelon, Kwang Hwan Kim, Jinpyo Hong & Sung Joong Lee
Publication title: Scientific Reports 12(1), December 2022

Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is accompanied by chronic neurological sequelae such as cognitive decline and mood disorder, but the underlying mechanisms have not yet been elucidated. We explored the possibility that the brain-infiltrating SARS-CoV-2 spike protein contributes to the development of neurological symptoms observed in COVID-19 patients in this study. Our behavioral study showed that administration of SARS-CoV-2 spike protein S1 subunit (S1 protein) to mouse hippocampus induced cognitive deficit and anxiety-like behavior in vivo. These neurological symptoms were accompanied by neuronal cell death in the dorsal and ventral hippocampus as well as glial cell activation. Interestingly, the S1 protein did not directly induce hippocampal cell death in vitro. Rather, it exerted neurotoxicity via glial cell activation, partially through interleukin-1β induction. In conclusion, our data suggest a novel pathogenic mechanism for the COVID-19-associated neurological symptoms that involves glia activation and non-cell autonomous hippocampal neuronal death by the brain-infiltrating S1 protein.
Full text link https://tinyurl.com/264ru32n

Article title: Hippocampal astrocytes modulate anxiety-like behavior
Springer Nature
Authors: Woo-Hyun Cho, Kyungchul Noh, Byung Hun Lee, Ellane Barcelon, Sang Beom Jun, Hye Yoon Park & Sung Joong Lee
Publication title: Nature Communications 13(1), November 2022

Abstract:
Astrocytes can affect animal behavior by regulating tripartite synaptic transmission, yet their influence on affective behavior remains largely unclear. Here we showed that hippocampal astrocyte calcium activity reflects mouse affective state during virtual elevated plus maze test using two-photon calcium imaging in vivo. Furthermore, optogenetic hippocampal astrocyte activation elevating intracellular calcium induced anxiolytic behaviors in astrocyte-specific channelrhodopsin 2 (ChR2) transgenic mice (hGFAP-ChR2 mice). As underlying mechanisms, we found ATP released from the activated hippocampal astrocytes increased excitatory synaptic transmission in dentate gyrus (DG) granule cells, which exerted anxiolytic effects. Our data uncover a role of hippocampal astrocytes in modulating mice anxiety-like behaviors by regulating ATP-mediated synaptic homeostasis in hippocampal DG granule cells. Thus, manipulating hippocampal astrocytes activity can be a therapeutic strategy to treat anxiety.
Full text link https://tinyurl.com/5n7xmzse

Article title: Development of novel, biocompatible, polyester amines for microglia-targeting gene delivery
Authors: Boomin Choi
Publication title: RSC Advances 11(58):36792-36800, November 2021

Abstract:
Recent progress in personalized medicine and gene delivery has created exciting opportunities in therapeutics for central nervous system (CNS) disorders. Despite the interest in gene-based therapies, successful delivery of nucleic acids for treatment of CNS disorders faces major challenges. Here we report the facile synthesis of a novel, biodegradable, microglia-targeting polyester amine (PEA) carrier based on hydrophilic triethylene glycol dimethacrylate (TG) and low-molecular weight polyethylenimine (LMW-PEI). This nanocarrier, TG-branched PEI (TGP), successfully condensed double-stranded DNA into a size smaller than 200 nm. TGP nanoplexes were nontoxic in primary mixed glial cells and showed elevated transfection efficiency compared with PEI-25K and lipofector-EZ. After intrathecal and intracranial administration, PEA nanoplexes delivered genes specifically to microglia in the spinal cord and brain, respectively, proposing TGP as a novel microglia-specific gene delivery nanocarrier. The microglia-specific targeting of the TGP nanocarrier offers a new therapeutic strategy to modulate CNS disorders involving aberrant microglia activation while minimizing off-target side effects.
Full text link https://tinyurl.com/s379fwfy

Article title: Effects of optogenetic astrocyte activation in hippocampus on mouse behavior
Authors: Woo-HyunCho, Kyungchul Noh, Ellane Barcelon, Sung Joong Lee
Publication title: IBRO Reports 6:S379, September 2019

Abstract:
Emerging data from recent investigations show that communication between neurons and astrocytes plays a critical role in brain functions and animal behaviors. For instance, astrocyte in brain stem and hypothalamus regulate respiration and mouse feeding behavior, respectively. However, the in vivo effects of astrocyte activation in hippocampus, a critical brain sub-region for cognitive and affective brain functions, on animal behaviors have not been addressed. To investigate the astrocyte function on animal behaviors in vivo, we generated hGFAPcreER/+:R26ChR2(H134R)EYFP/+ transgenic mice in which ChR2 is specifically expressed in astrocytes in the brain. Upon elevating astrocyte calcium activity by optogenetic stimulation, we demonstrate that hippocampal astrocyte controls fear memory and innate anxiety behaviors by regulating granule cells activity. Our findings show that alteration of hippocampal astrocyte activity has a profound impact on hippocampal neural activity and thereby cognitive or affective behaviors.
Full text link https://tinyurl.com/mu5x63xf

Article title: Brain microglial activation in chronic pain-associated affective disorder
Authors: Ellane Barcelon, Woo-Hyun Cho, Sang Beom Jun, Sung Joong Lee
Publication title: IBRO Reports 6:S381, September 2019

Abstract:
A growing body of evidence from both clinical and animal studies indicates that chronic neuropathic pain is associated with comorbid affective disorders. Spinal cord microglial activation is involved in nerve injury-induced pain hypersensitivity characterizing neuropathic pain. However, there is a lack of thorough assessments of microglial activation in the brain after nerve injury. In the present study, we characterized microglial activation in brain sub-regions of CX3CR1GFP/+ mice after chronic constriction injury (CCI) of the sciatic nerve, including observations at delayed time points when affective brain dysfunctions such as depressive-like behaviors typically develop. Mice manifested chronic mechanical hypersensitivity immediately after CCI and developed depressive-like behaviors 8 weeks post-injury. Concurrently, significant increases of soma size and microglial cell number were observed in the medial prefrontal cortex (mPFC), hippocampus, and amygdala 8 weeks post-injury. Transcripts of CD11b, and TNF-α, genes associated with microglial activation or depressive-like behaviors, are correspondingly upregulated in these brain areas. Our results demonstrate that microglia are activated in specific brain sub-regions after CCI at delayed time points and imply that brain microglial activation plays a role in chronic pain-associated affective disorders.
Full text link https://tinyurl.com/yck8kvmn

Article title: Optogenetic Glia Manipulation: Possibilities and Future Prospects
Authors: Woo-Hyun Cho, Ellane Barcelon, and Sung Joong Lee
Publication title: Experimental Neurobiology 25(5):197-204, October 2016

Abstract:
Our brains are composed of two distinct cell types: neurons and glia. Emerging data from recent investigations show that glial cells, especially astrocytes and microglia, are able to regulate synaptic transmission and thus brain information processing. This suggests that, not only neuronal activity, but communication between neurons and glia also plays a key role in brain function. Thus, it is currently well known that the physiology and pathophysiology of brain function can only be completely understood by considering the interplay between neurons and glia. However, it has not yet been possible to dissect glial cell type-specific roles in higher brain functions in vivo. Meanwhile, the recent development of optogenetics techniques has allowed investigators to manipulate neural activity with unprecedented temporal and spatial precision. Recently, a series of studies suggested the possibility of applying this cutting-edge technique to manipulate glial cell activity. This review briefly discusses the feasibility of optogenetic glia manipulation, which may provide a technical innovation in elucidating the in vivo role of glial cells in complex higher brain functions.
Full text link https://tinyurl.com/nhcadp3t