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个人简介
Work at UCLA has consistently produced significant discoveries with a major impact on basic and clinical neuroscience. My work focused on hypocretin (or orexin) and the pathological changes in human Narcolepsy, Parkinson's disease, opioid addiction, and obesity.
The first study to pinpoint the cause of Narcolepsy in humans reported (Thannickal et al., Neuron 27: 469-474, 2000) 90% hypocretin cell loss. Further studies (Science 298:767, 2002, Brain Pathology 3:340-51, 2003, Neurology 25:1189-92, 2005, Sleep 32: 993-8, 2009) elaborated the initial findings. We found that Narp cells are co-localized with hypocretin depleted to the same extent as hypocretin cells in the hypothalamus. The patients without cataplexy had a localized loss of hypocretin neurons restricted to the posterior hypothalamus.
In 2007, discovered that Parkinson's disease patients have a loss of hypocretin and melanin-concentrating neurons which was correlated with the severity of the disease (Brain 130:1586-95, 2007, and Brain 131: 1, e87, 2008). It is a significant finding within 190 years of Parkinson's Research.
The number of histamine neurons is increased by 64% in human narcoleptics (Ann Neurology 74:786-93, 2013). This is the first report to show a massive increase in neurons in one part of the adult human brain in compensation for the loss of neurons in a different region. The possibility of restoring function by assisting that process gives new hope to our patients who suffer from Alzheimer's and Parkinson's disease.
Hypocretin role in Opioid addiction and Opioid for treatment of Narcolepsy. This is a significant finding 214 years after the first synthetic Opioid – Morphine – was discovered (Thannickal et al., Science Translational Medicine 10(447):eaao 4953.doi: 0.1126/scitransl med. aao4953, 2018). We found that human heroin addicts have 54% more hypocretin-producing neurons than neurologically normal individuals. This work demonstrates that opiates can permanently alter the number of hypocretin neurons. Opiate administration can reverse the neuronal loss seen in murine Narcolepsy and can reverse the symptoms of Narcolepsy.
In 2019, we found hypocretin neuronal loss in obese people. The loss of hypocretin cells (ranging from 10% to 68%) was correlated with increased BMI. Glial fibrillary acidic protein cell numbers were significantly increased with BMI ( Society for Neuroscience, S-7071, 2019). This study shows narcolepsy-like pathology in human obesity. Hypocretin or its agonists may be a therapeutic target for treating obesity.
研究兴趣
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bioRxiv : the preprint server for biology (2024)
Thomas C Thannickal, Joshi John,Ling Shan,Dick F Swaab, Ming-FungWu, Lalini, Ramanathan,Ronald McGregor, Keng-Tee Chew,Marcia Cornford, Y Akihiro, Yamanaka,
semanticscholar(2017)
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World Journal of Neurologyno. 3 (2015)
Orexin and Sleeppp.289-298, (2015)
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