Hui Shen, Ph.D.

@article{Biase2017,

title = {Local Cues Establish and Maintain Region-Specific Phenotypes of Basal Ganglia Microglia.},

author = {Lindsay M De Biase and Kornel E Schuebel and Zachary H Fusfeld and Kamwing Jair and Isobel A Hawes and Raffaello Cimbro and Hai-Ying Zhang and Qing-Rong Liu and Hui Shen and Zheng-Xiong Xi and David Goldman and Antonello Bonci},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28689984},

doi = {10.1016/j.neuron.2017.06.020},

issn = {1097-4199 (Electronic); 0896-6273 (Linking)},

year  = {2017},

date = {2017-07-19},

journal = {Neuron},

volume = {95},

number = {2},

pages = {341--356},

address = {Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA. Electronic address: lindsay.debiase@nih.gov.},

abstract = {Microglia play critical roles in tissue homeostasis and can also modulate neuronal function and synaptic connectivity. In contrast to astrocytes and oligodendrocytes, which arise from multiple progenitor pools, microglia arise from yolk sac progenitors and are widely considered to be equivalent throughout the CNS. However, little is known about basic properties of deep brain microglia, such as those within the basal ganglia (BG). Here, we show that microglial anatomical features, lysosome content, membrane properties, and transcriptomes differ significantly across BG nuclei. Region-specific phenotypes of BG microglia emerged during the second postnatal week and were re-established following genetic or pharmacological microglial ablation and repopulation in the adult, indicating that local cues play an ongoing role in shaping microglial diversity. These findings demonstrate that microglia in the healthy brain exhibit a spectrum of distinct functional states and provide a critical foundation for defining microglial contributions to BG circuit function.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{McDevitt:2014aab,

title = {Serotonergic versus nonserotonergic dorsal raphe projection neurons: differential participation in reward circuitry.},

author = {Ross A McDevitt and Alix Tiran-Cappello and Hui Shen and Israela Balderas and Jonathan P Britt and Rosa A M Marino and Stephanie L Chung and Christopher T Richie and Brandon K Harvey and Antonello Bonci},

url = {https://www.ncbi.nlm.nih.gov/pubmed/25242321},

doi = {10.1016/j.celrep.2014.08.037},

issn = {2211-1247 (Electronic)},

year  = {2014},

date = {2014-09-25},

journal = {Cell Rep},

volume = {8},

number = {6},

pages = {1857--1869},

address = {Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA.},

abstract = {The dorsal raphe nucleus (DRN) contains the largest group of serotonin-producing neurons in the brain and projects to regions controlling reward. Although pharmacological studies suggest that serotonin inhibits reward seeking, electrical stimulation of the DRN strongly reinforces instrumental behavior. Here, we provide a targeted assessment of the behavioral, anatomical, and electrophysiological contributions of serotonergic and nonserotonergic DRN neurons to reward processes. To explore DRN heterogeneity, we used a simultaneous two-vector knockout/optogenetic stimulation strategy, as well as cre-induced and cre-silenced vectors in several cre-expressing transgenic mouse lines. We found that the DRN is capable of reinforcing behavior primarily via nonserotonergic neurons, for which the main projection target is the ventral tegmental area (VTA). Furthermore, these nonserotonergic projections provide glutamatergic excitation of VTA dopamine neurons and account for a large majority of the DRN-VTA pathway. These findings help to resolve apparent discrepancies between the roles of serotonin versus the DRN in behavioral reinforcement.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Luo:2013aa,

title = {CART peptide induces neuroregeneration in stroke rats.},

author = {Yu Luo and Hui Shen and Hua-Shan Liu and Seong-Jin Yu and David J Reiner and Brandon K Harvey and Barry J Hoffer and Yihong Yang and Yun Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/23211962},

doi = {10.1038/jcbfm.2012.172},

issn = {1559-7016 (Electronic); 0271-678X (Linking)},

year  = {2013},

date = {2013-02-01},

journal = {J Cereb Blood Flow Metab},

volume = {33},

number = {2},

pages = {300--310},

address = {National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, USA.},

abstract = {Utilizing a classic stroke model in rodents, middle cerebral artery occlusion (MCAo), we describe a novel neuroregenerative approach using the repeated intranasal administration of cocaine- and amphetamine-regulated transcript (CART) peptide starting from day 3 poststroke for enhancing the functional recovery of injured brain. Adult rats were separated into two groups with similar infarction sizes, measured by magnetic resonance imaging on day 2 after MCAo, and were treated with CART or vehicle. The CART treatment increased CART level in the brain, improved behavioral recovery, and reduced neurological scores. In the subventricular zone (SVZ), CART enhanced immunolabeling of bromodeoxyuridine, a neural progenitor cell marker Musashi-1, and the proliferating cell nuclear antigen, as well as upregulated brain-derived neurotrophic factor (BDNF) mRNA. AAV-GFP was locally applied to the SVZ to examine migration of SVZ cells. The CART enhanced migration of GFP(+) cells from SVZ toward the ischemic cortex. In SVZ culture, CART increased the size of neurospheres. The CART-mediated cell migration from SVZ explants was reduced by anti-BDNF blocking antibody. Using (1)H-MRS (proton magnetic resonance spectroscopy), increases in N-acetylaspartate levels were found in the lesioned cortex after CART treatment in stroke brain. Cocaine- and amphetamine-regulated transcript increased the expression of GAP43 and fluoro-ruby fluorescence in the lesioned cortex. In conclusion, our data suggest that intranasal CART treatment facilitates neuroregeneration in stroke brain.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Shen:2009aa,

title = {Astaxanthin reduces ischemic brain injury in adult rats.},

author = {Hui Shen and Chi-Chung Kuo and Jenny Chou and Alice Delvolve and Shelley N Jackson and Jeremy Post and Amina S Woods and Barry J Hoffer and Yun Wang and Brandon K Harvey},

url = {https://www.ncbi.nlm.nih.gov/pubmed/19218497},

doi = {10.1096/fj.08-123281},

issn = {1530-6860 (Electronic); 0892-6638 (Linking)},

year  = {2009},

date = {2009-06-01},

journal = {FASEB J},

volume = {23},

number = {6},

pages = {1958--1968},

address = {National Institute on Drug Abuse, NIH, 251 Bayview Blvd., Baltimore, MD 21224, USA.},

abstract = {Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Shen:2005aa,

title = {Inosine reduces ischemic brain injury in rats.},

author = {Hui Shen and Guann-Juh Chen and Brandon K Harvey and Paula C Bickford and Yun Wang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/15692110},

doi = {10.1161/01.STR.0000155747.15679.04},

issn = {1524-4628 (Electronic); 0039-2499 (Linking)},

year  = {2005},

date = {2005-05-01},

journal = {Stroke},

volume = {36},

number = {3},

pages = {654--659},

address = {National Institute on Drug Abuse, National Institutes of Health, Baltimore, Md, USA.},

abstract = {BACKGROUND AND PURPOSE: Purinergic nucleoside inosine elicits protection and regeneration during various injuries. The purpose of this study was to examine the protective effects of inosine against cerebral ischemia. METHODS: Adult Sprague-Dawley rats were anesthetized. Inosine, hypoxathine, or vehicle was administered intracerebroventricularly before transient right middle cerebral artery occlusion (MCAo). Animals were placed in behavioral chambers 2 days to 2 weeks after MCAo and then euthanized for tri-phenyl-tetrazolium chloride staining. Glutamate release was measured by microdialysis/high-performance liquid chromatography, and single-unit action potentials were recorded from neurons in the parietal cortex. RESULTS: Stroke animals receiving inosine pretreatment demonstrated a higher level of locomotor activity and less cerebral infarction. Intracerebroventricular administration of the same dose of hypoxanthine did not confer protection. Coadministration of selective A3 receptor antagonist 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1, 4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS1191) significantly reduced inosine-mediated protection. Inosine did not alter basal glutamate release, nor did it reduce ischemia-evoked glutamate overflow from cerebral cortex. However, inosine antagonized glutamate-induced electrophysiological excitation in cerebral cortical neurons. CONCLUSIONS: Inosine inhibits glutamate postsynaptic responses and reduces cerebral infarction. Its protective effect against ischemia/reperfusion-related insults may involve activation of adenosine A3 receptors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}