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N, N-dimethyltryptamine, a natural psychedelic, rapidly improves spatial memory and hippocampal longterm potentiation: a potential rapid-acting therapy for dementia-associated wandering

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中国药理学与毒理学杂志 2023年第7期37卷 489-490页

作者： CHENG Dan LEI Zhuogui Benjamin Chun-Kit TONG catherine kin chiu LI Ying king-Ho CHEUNG ZHANG Zhangjin School of Chinese Medicine the University of HongKong Department of Neuroscience City University of HongKong School of Chinses Medicine and Mr. and Mrs. Ko Chi Ming Centre for Parkinson’s Disease Research HongKong Baptist University Department of Psychology LKS Faculty of Medicine the University of HongKong Department of Chinese Medicine the University of Hong Kong-Shenzhen Hospital

There is no fast-acting treatment strategies against Alzheimer′s disease(AD), in particular dementia-related wandering. N, N-dimethyltryptamine(DMT) is a natural psychedelic that may have rapid-onset nootropic effects. In this study, 5 × FAD transgenic mice which recapitulated amyloid neuropathological features of AD received one single injection of 6 or 12 mg · kg-1DMT and tested at 0.5, 1, and 2 h thereafter in Y-maze for spatial memory. 5×FAD transgenic mice exhibited pronounced decreases in time spent, number entered, and distance travelled in the novel arm of Y-maze. DMT at 12 mg · kg-1partially or completely reversed the three behavioral indices at multiple time points, up to 2 h post injection. The rapid-onset behavioral improvement was consistent with pharmacokinetic analysis of DMT, showing approximately 30 min to reach the maximum concentration in the brain tissue. The transgenic mice also displayed dramatically impaired hippocampal long-term potentiation(LTP), an electrophysiological feature of memory formation and consolidation. DMT potently enhanced LTP and restored intracellular calcium activity, expression and phosphorylation of calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ) and AMPA-type glutamate receptor1(GluR1), the two key calcium-activated mediators involved in LTP induction. Adenosine triphosphate(ATP)is purinergic signalling molecules that are involved in LTP induction and maintenance. DMT rapidly increased mitochondrial ATP dynamics in in vivo and in vitro *** results suggest that DMT rapidly improve spatial memory and hippocampal LTP by restoring the CaMKⅡ-GluR1 signaling pathway and mitochondrial ATP production. It may be served as a fast-acting nootropic agent for the treatment of AD in particular wandering.

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Contrasting neuropathology and functional recovery after spinal cord injury in developing and adult rats

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Neuroscience Bulletin 2013年第4期29卷 509-516页

作者： Qiuju Yuan Huanxing Su kin chiu Wutian Wu Zhi-Xiu Lin Department of Anatomy The University of Hong Kong School of Chinese Medicine Faculty of Science The Chinese University of Hong Kong State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences University of Macao State Key Laboratory of Brain and Cognitive Sciences Development and Growth Li Ka Shing Faculty of Medicine The University of Hong Kong Research Center of Reproduction Development and Growth Li Ka Shing Faculty of Medicine The University of Hong Kong GHM Institute of CNS Regeneration Jinan University

Conflicting findings exist regarding the link between functional recovery and the regrowth of spinal tracts across the lesion leading to the restoration of functional contacts. In the present study, we investigated whether functional locomotor recovery was attributable to anatomical regeneration at postnatal day 1 （PN1）, PN7, PN14 and in adult rats two months after transection injury at the tenth thoracic segment of the spinal cord. The Basso, Beattie, and Bresnahan scores showed that transection led to a failure of hindlimb locomotor function in PN14 and adult rats. However, PN1 and PN7 rats showed a significant level of stepping function after complete spinal cord transection. Unexpectedly, unlike the transected PN14 and adult rats in which the spinal cord underwent limited secondary degeneration and showed a scar at the lesion site, the rats transected at PN1 and PN7 showed massive secondary degeneration both anterograde and retrograde, leaving a 〉5-mm gap between the two stumps. Furthermore, retrograde tracing with fluorogold （FG） also showed that FG did not cross the transection site in PN1 and PN7rats as in PN14 and adult rats, and re-transection of the cord caused no apparent loss in locomotor performance in the rats transected at PN1. Thus, these three lines of evidence strongly indicated that the functional recovery after transection in neonatal rats is independent of regrowth of spinal tracts across the lesion site. Our results support the notion that the recovery of locomotor function in developing rats may be due to intrinsic adaptations in the spinal circuitry below the lesion that control hindlimb locomotor activity rather than the regrowth of spinal tracts across the lesion. The difference in secondary degeneration between neonatal and adult rats remains to be explored.

关键词： neonatal spinal cord injury regeneration functional recovery rat

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Modulation of morphological changes of microglia and neuroprotection by monocyte chemoattractant protein-1 in experimental glaucoma

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Cellular & Molecular Immunology 2010年第1期7卷 61-68页

作者： kin chiu Sze-Chun Yeung Kwok-Fai So Raymond Chuen-Chung Chang Laboratory of Neurodegenerative Diseases Department of AnatomyUniversity of Hong KongPokfulamHong KongChina State Key Laboratory of Brain and Cognitive Sciences University of HongKongPokfulamHongKongChina Research Centre of Heart BrainHormone and Healthy AgingLiKa Shing Faculty of MedicineUniversity of Hong KongPokfulamHong KongChina

Monocyte chemoattractant protein-1(MCP-1)/CCL2 is a C–C chemokine involved in the activation and recruitment of monocytic cells to injury ***-1/CCL2 can induce either neuroprotection or neurodestruction in vitro,depending on the experimental *** aim to use MCP-1/CCL2 as an experimental tool to investigate the morphological changes of microglia when loss of healthy retinal ganglion cells(RGCs)is exacerbated or attenuated in an experimental glaucoma *** a high concentration(1000 ng)of MCP-1/CCL2 and lipopolysaccharide(LPS)-exacerbated RGC loss,100 ng MCP-1/CCL2 provided neuroprotection towards *** MCP-1/CCL2(100 ng)also upregulated insulin-like growth factor-1(IGF-1)immunoreactivity in the *** neuroprotective effect of MCP-1/CCL2 was not due to the massiveinfiltration of microglia/*** together,this is the first report showing that an appropriate amount of MCP-1/CCL2 can protect RGCs in experimental glaucoma.

关键词： glaucoma IGF-1 MCP-1/CCL2 microglia neuroprotection

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Modulation of Neuroimmune Responses on Glia in the Central Nervous System： Implication in Therapeutic Intervention against Neuroinflammation

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Cellular & Molecular Immunology 2009年第5期6卷 317-326页

作者： Raymond Chuen-Chung Chang kin chiu Yuen-Shan Ho Kwok-Fai So Laboratory of Neurodegenerative Diseases Depamnent of Anatomy LKSFaculty of Medicine University of Hong Kong Pokfulam Hong KongSAR China Research Centre of Heart Brain Hormone and Healthy Aging LKSFaculty of Medicine University of Hong Kong Pokfulam Hong KongSAR China State Key Laboratory for Brain and Cognitive Sciences University of HongKong. Pokfulam Hong Kong SAR China Department of Anatomy LKS Faculty of Miedicine The University of Hong Kong Rm.

It has long been known that the brain is an immunologically privileged site in normal conditions. Although the cascade of immune responses can occur as long as there is a neuronal injury or a potent immune stimulation, how the brain keeps glial cells in a quiescent state is still unclear. Increasing efforts have been made by several laboratories to elucidate how repression oi~ immune responses is achieved in the neuronal environment. The suppression factors include neurotransmitters, neurohormones, neurotrophic factors, anti-inflammatory factors, and cell-cell contact via adhesion molecules or CD200 receptor. This review discusses how these factors affect the cascade of cerebral immune responses because no single factor listed above can fully account for the immune suppression. While several factors contribute to the suppression of immune responses, activation of glial cells and their production of pro-inflammatory factors do occur as long as there is a neuronal injury, suggesting that some neuronal components facilitate immune responses. This review also discusses which signals initiate or augment cerebral immune responses so that stimulatory signals override the suppressive signals. Increasing lines of evidence have demonstrated that immune responses in the brain are not always detrimental to neurons. Attempt to simply clear off inflammatory factors in the CNS may not be appropriate for neurons in neurological disorders. Appropriate control of immune cells in the CNS may be beneficial to neurons or even neuroregeneration. Therefore, understanding the mechanisms underlying immune suppression may help us to reshape pharmacological interventions against inflammation in many neurological disorders.

关键词： neural cell adhesion molecule neurotrophins potassium ions microglia neuroinflammation

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CircTUBD1: A Novel Circular RNA Molecule as a Therapeutic Target in Radiation-induced Liver Fibrosis

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Journal of Clinical and Translational Hepatology 2022年第4期10卷 571-573页

作者： catherine Yujia Gu Terence kin Wah Lee Department of Applied Biology and Chemical Technology The Hong Kong Polytechnic UniversityHong KongChina State Key Laboratory of Chemical Biology and Drug Discovery The Hong Kong Polytechnic UniversityHong KongChina

Citation of this article:Gu CY,Lee ***1:A Nov-el Circular RNA Molecule as a Therapeutic Target in Radiation-induced Liver Fibrosis.J Clin Transl Hepatol 2022;10(4):***:10.14218/*** liver cancer is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer mortality worldwide.1 Liver transplantation and surgical resection are two curative therapeutic options for liver cancer patients at the early ***,most patients are diagnosed at advanced stages.

关键词： Liver Therapeutic cancer

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More than anti-malarial agents: therapeutic potential of artemisinins in neurodegeneration

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Neural Regeneration Research 2019年第9期14卷 1494-1498页

作者： Bing-Wen Lu Larry Baum Kwok-Fai So kin chiu Li-Ke Xie Department of Ophthalmology Eye HospitalChina Academy of Chinese Medical SciencesBeijingChina Department of Ophthalmology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administration RegionChina State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administration RegionChina Center for Genomic Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Li Ka Shing Faculty of MedicineHong Kong Special Administration RegionChina Department of Psychiatry Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Li Ka Shing Faculty of MedicineHong Kong Special Administration RegionChina GHM Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Funding:This

Artemisinin,also called qinghaosu,is originally derived from the sweet wormwood plant(Artemisia annua),which is used in traditional Chinese *** and its derivatives(artemisinins)have been widely used for many years as anti-malarial agents,with few adverse side ***,evidence has recently shown that artemisinins might have a therapeutic value for several other diseases beyond malaria,including cancers,inflammatory diseases,and autoimmune *** is a challenging age-associated neurological disorder characterized by deterioration of neuronal structures as well as functions,whereas neuroinflammation has been considered to be an underlying factor in the development of various neurodegenerative disorders,including Alzheimer’s *** discovered properties of artemisinins suggested that they might be used to treat neurodegenerative disorders by decreasing oxidation,inflammation,and amyloid beta protein(Aβ).In this review,we will introduce artemisinins and highlight the possible mechanisms of their neuroprotective activities,suggesting that artemisinins might have therapeutic potential in neurodegenerative disorders.

关键词： artemisinin inflammation neuroinflammation neurodegeneration Alzheimer’s disease Parkinson’s disease Aβ anti-oxidation neuroprotection neural regeneration

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Suppression of innate antiviral response by severe acute respiratory syndrome coronavirus M protein is mediated through the first transmembrane domain

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Cellular & Molecular Immunology 2014年第2期11卷 141-149页

作者： Kam-Leung Siu Chi-Ping Chan kin-Hang Kok Patrick chiu-Yat Woo Dong-Yan Jin Department of Biochemistry The University of Hong Kong Pokfulam Hong Kong Department of Microbiology The University of Hong KongPokfulam Hong Kong

Coronaviruses have developed various measures to evade innate immunity, We have previously shown that severe acute respiratory syndrome （SARS） coronavirus M protein suppresses type I interferon （IFN） production by impeding the formation of functional TRAF3-containing complex. In this study, we demonstrate that the IFN-antagonizing activity is specific to SARS coronavirus M protein and is mediated through its first transmembrane domain （TM 1） located at the N terminus. M protein from human coronavirus HKU 1 does not inhibit IFN production. Whereas N-linked glycosylation of SARS coronavirus M protein has no influence on IFN antagonism, TM1 is indispensable for the suppression of IFN production. TM 1 targets SARS coronavirus M protein and heterologous proteins to the Golgi apparatus, yet Golgi localization is required but not sufficient for IFN antagonism. Mechanistically, TM 1 is capable of binding with RIG-I, TRAF3, TBK1 and IKK~, and preventing the interaction of TRAF3 with its downstream effectors. Our work defines the molecular architecture of SARS coronavirus M orotein reouired for suooression of innate antiviral re^nnn^e.

关键词： human coronavirus HKU1 innate antiviral response SARS coronavirus TRAF3 type I interferons

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Lycium barbarum extract promotes M2 polarization and reduces oligomeric amyloid-β-induced inflammatory reactions in microglial cells

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Neural Regeneration Research 2022年第1期17卷 203-209页

作者： Zhong-Qing Sun Jin-Feng Liu Wei Luo Ching-Hin Wong Kwok-Fai So Yong Hu kin chiu Department of Ophthalmology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administrative RegionChina Guangdong-Hong Kong-Macao Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Orthopaedics&Traumatology The University of Hong KongHong Kong Special Administrative RegionChina

Lycium barbarum(LB)is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions,such as antioxidation,neuroprotection,and immune *** of the main mechanisms of Alzheimer’s disease is that microglia activated by amyloid beta(Aβ)transform from the resting state to an M1 state and release pro-inflammatory cytokines to the surrounding *** the present study,immortalized microglial cells were pretreated with *** extract for 1 hour and then treated with oligomeric Aβfor 23 *** results showed that LB extract significantly increased the survival of oligomeric Aβ-induced microglial cells,downregulated the expression of M1 pro-inflammatory markers(inducible nitric oxide synthase,tumor necrosis factorα,interleukin-6,and interleukin-1β),and upregulated the expression of M2 anti-inflammatory markers(arginase-1,chitinase-like protein 3,and interleukin-4).LB extract also inhibited the oligomeric Aβ-induced secretion of tumor necrosis factorα,interleukin-6,and interleukin-1βin microglial *** results of in vitro cytological experiments suggest that,in microglial cells,LB extract can inhibit oligomeric Aβ-induced M1 polarization and concomitant inflammatory reactions,and promote M2 polarization.

关键词： Alzheimer’s disease amyloid-β anti-inflammatory factors Lycium barbarum extract M1 microglia M2 microglia neuroinflammation proinflammatory factors

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Effect of Lycium barbarum Polysaccharides on the expression of endothelin-1 and its receptors in an ocular hypertension model of rat glaucoma

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Neural Regeneration Research 2012年第9期7卷 645-651页

作者： Xue-Song Mi kin chiu Geoffrey Van Justin Wai Chung Leung Amy Cheuk Yin Lo SookjaKim Chung Raymond Chuen-Chung Chang Kwok-Fai So Department of Anatomy and the State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong Special Administrative RegionChina Eye Institute Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong Special Administrative RegionChina Research Centre of Heart BrainHormone and Healthy AgingLi Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong Kong Special Administrative RegionChina The Joint Laboratory for Brain Function and Health （BFAH） Jinan University and The University of Hong Kong Guangzhou 510632Guangdong Province China

Lycium barbarum, a traditional Chinese anti-aging herb, has been shown to protect retinal ganglion cells （RGCs） in a rat chronic ocular hypertension （COH） model. Here, we investigated the expression of endothelin-1 （ET-1）, a strong vasoconstrictor, and its receptors, ETA and ETB, in the COH model and assessed the effects of Lycium barbarum on the ET-1 axis. Elevated intraocular pressure （IOP） was induced in the right eye of SD rats using argon laser photocoagulation. （1） The expression of ET-1, ETA and ETB in normal and COH retinas was studied. （2） Some COH rats were fed daily with Lycium barbarum Polysaccharides （LBP） using 1 mg/kg or phosphate-buffered saline （PBS） for 3 weeks （started 1 week before photocoagulation）. The effects of LBP on the expression of ET-1 and its receptors, ETA and ETB, in COH retina were evaluated. A semi-quantitative analysis of staining intensity was used to evaluate the expression levels of ET-1, ETA and ETB in retinal vasculature. We found that （1） Under COH condition, the immunoreactivity of ET-1 was increased in retina associated with an increase of ETB receptor immunoreactivity and a decrease of ETA receptor immunoreactivity. （2） After feeding COH rats with LBP, the expression of ET-1 was decreased with an increase of ETA expression and a decrease of ETB expression in the retina, especially in RGCs. （3） By comparing the staining intensity in the vasculature of COH retina in LBP-fed group with PBS-fed group, there was a decrease in the expression of ET-1 and ETA and an increase in ETB. In summary, ET-1 expression was up-regulated in the retina in COH model. LBP could decrease the expression of ET-1 and modulate the expression of its receptors, ETA and ETB, under the condition of COH. The neuroprotective effect of LBP on RGCs might be related to its ability to regulate the ET-1-mediated biological effects on RGCs and retinal vasculature.

关键词： retinal ganglion cell Lycium barbarum Polysaccharides glaucoma endothelin-1

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Mechanisms of electrical stimulation in eye diseases:A narrative review

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Advances in Ophthalmology Practice and Research 2022年第2期2卷 1-10页

作者： Jinfeng Liu Andre K.H.Ma Kwok Fai So Vincent W.H.Lee kin chiu Department of Ophthalmology The University of Hong KongSARHong KongChina Harrow School HarrowUK The State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongSARHong KongChina Department of Psychology The University of Hong KongSARHong KongChina Guangdong-Hong Kong-Macao Institute of Central Nervous System Regeneration Jinan UniversityGuangzhouChina

Background:In the last two decades,electrical stimulation(ES)has been tested in patients with various eye diseases and shows great treatment potential in retinitis pigmentosa and optic ***,the clinical application of ES in ophthalmology is currently *** the one hand,optimization and standardization of ES protocols is still an unmet *** the other hand,poor understanding of the underlying mechanisms has hindered clinical *** Text:Numerous experimental studies have been conducted to identify the treatment potential of ES in eye diseases and to explore the related cellular and molecular *** this review,we summarized the in vitro and in vivo evidence related to cellular and tissue response to ES in eye *** highlighted several pathways that may be utilized by ES to impose its effects on the diseased ***:Therapeutic effect of ES in retinal degenerative diseases might through preventing neuronal apoptosis,promoting neuronal regeneration,increasing neurotrophic factors production in Müller cells,inhibiting microglial activation,enhancing retinal blood flow,and modulating brain *** studies are suggested to analyse changes in specific retinal cells for optimizing the treatment parameters and choosing the best fit ES delivery method in target diseases.

关键词： Electrical stimulation Eye diseases Ophthalmology Retinitis pigmentosa Optic neuropathy

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