Department：Neurology
Medical School：University of Science and Technology of China, School of Life Sciences, China
Academic Rank：Professor
Neurobiological mechanisms of neuropsychiatric diseases
The 12th Zhejiang University Lin Baixin High-Tech Award, First Prize, 2017
Zhejiang University Medical School Scientific Research Contribution Award, 2016
Natural Science Award of the Ministry of Education of China, Second Prize, 2014
Zhejiang University Medical School Scientific Research Contribution Award, 2014
Zhejiang University Medical School Scientific Research Contribution Award, 2013
Zhejiang University Medical School Scientific Research Contribution Award, 2012
General Secretary, International Neuroendocrine Federation, 2020-2024
Vice Chairman, Human Brain Research Branch of Chinese Anatomical Society, 2015-present
Deputy Secretary General, Stress Neurobiology Branch of Chinese Neuroscience Society, 2017-2020
Council Member, Zhejiang Neuroscience Society, 2013-present
Vice Director, Popular Science Working Committee of Zhejiang Neuroscience Society, 2018-present
Visiting Professor, Netherlands Institute of Neuroscience
Neuropsychiatric diseases have been ranked very high, or the top, of the total disease-burden. It becomes therefore urgent to explore the pathogenesis of these diseases in order to develop adequate prevention and treatment strategies. Genetic and environmental (epigenetic) factors may both play a role in the pathogenesis of brain disorders, which are extremely difficult to model with experimental animals - while some symptoms may be reproduced, no animal model recapitulates a full blown brain disease at present. In addition, these animal models need to be validated in human brains. We therefore believe that to decode the genetic, epigenetic, molecular and pathogenic underpinning of brain functions there is no alternative than directly studying the human brain. This is our lab's focus: postmortem human brain study.
At present, there are 2 main research lines:
(1) Depression. Our hypothesis is that factors involved in the heterogeneous pathogenesis of depression include polymorphisms in genes, gender, age, developmental history and environmental stressors. They may make different brain systems vulnerable in a variable way to different stressful life events, causing alterations in a network mediated by neurotransmitters and neuromodulators, which finally make individuals in a personal way at risk for depression. With postmortem human brain material that is clinically and neuropathologically well characterized, animal models mimicking depression and molecular mechanistic work on cell lines, we try to elucidate the specific changes and the interaction in these molecular systems in relation to special subtypes of depression. The final aim is to set up tailor-made treatment for depressive patients.
(2) Alzheimer's diseases (AD). Our hypothesis is 'Use it or lose it', which is based upon our observations that the higher the brain function, the lower the chance for AD. This has recently been confirmed by our findings that during the course of AD as marked by Braak stages, quite a lot of brain areas including prefrontal cortex experienced a first increase then decrease (up-down) pattern of function change, implying that the brain knows the start of AD and it has certain self-rescue, or compensation, mechanism to keep its function well during the early stage of AD. We are trying to make clear these first molecular AD changes, which might be beneficial for AD therapy.
In addition, we also use i) cell and animal models that are validated in the clinical situation, and ii) blood and cerebrospinal fluid obtained from living patients to measure the hormones and neuroactive compounds involved in the diseases to investigate functional alterations that underlying mechanism.
Yang-Jian Qi, Zheng Fang, Zhong Ren, Juan-Li Wu, Lei Guo, Hong Tan, Man-Li Huang, Yi Shen*, Ai-Min Bao*. Rapid membrane effect of estrogens on stimulation of corticotropin-releasing hormone. Psychoneuroendocrinology. 2020;117:104680.
Bao AM*, Swaab DF. The human hypothalamus in mood disorders: the HPA axis in the center. IBRO Reports 6 (2019):45-53.
Guo L, Stormmesand J, Fang Z, Zhu Q, Balesar R, van Heerikhuize J, Sluiter A, Swaab DF, Bao AM*. Quantification of tyrosine hydroxylase and ErbB4 in the locus coeruleus of mood disorder patients: using a multispectral method to prevent interference with immunocytochemical signals by neuromelanin. Neurosci Bull. 2019 Apr; 35(2):205-215.
Zhu QB, Bao AM*, Swaab D. Activation of the Brain to Postpone Dementia: A Concept Originating from Postmortem Human Brain Studies. Neurosci Bull. 2019 Apr; 35(2):253-266.
Hu YT, Chen XL, Huang SH, Zhu QB, Yu SY, Shen Y, Sluiter A, Verhaagen J, Zhao J, Swaab DF, Bao AM*. Early Growth response-1 regulates acetylcholinesterase and its relation with the course of Alzheimer's disease. Brain Pathol. 2019 Jul;29(4):502-512.
Cao SX, Zhang Y, Hu XY, Hong B, Sun P,He HY, Geng HY, Bao AM, Duan SM, Yang JM, Gao TM, Lian H, Li XM. ErbB4 deletion in noradrenergic neurons in the locus coeruleus induces mania-like behavior via elevated catecholamines. Elife. 2018 Sep 4;7. pii: e39907.
Guo L, Chen YX, Hu YT, Wu XY, He Y, Wu JL, Huang ML, Mason M, Bao AM*. Sex hormones affect acute and chronic stress responses in sexually dimorphic patterns: Consequences for depression models. Psychoneuroendocrinology. 2018 May 21;95:34-42.
Bao AM*, Swaab DF. The art of matching brain tissue from patients and controls for postmortem research. Handb Clin Neurol. 2018;150:197-217.
Wu XY, Balesar R, Lu J, Farajnia S, Zhu QB, Huang ML, Bao AM*, Swaab DF. Increased glutamic acid decarboxylase expression in the hypothalamic suprachiasmatic nucleus in depression. Brain Struct Funct. 2017 Dec;222(9):4079-4088.
Dai D, Li QC, Zhu QB, Hu SH, Balesar B, Swaab DF, Bao AM*. Direct involvement of androgen receptor in oxytocin gene expression: possible relevance for mood disorders. Neuropsychopharmacology. 2017 Sep;42(10):2064-2071.
Lu J, Zhao J, Balesar R, Fronczekd R, Zhu QB, Wu XY, Hu SH, Bao AM*, Swaab DF. Sexually dimorphic changes of hypocretin (orexin) in depression. EBioMedicine 18 (2017) 311–319.
Wu JL, He Y, Hrubý R, Balesar R, Qi YJ, Guo L, Ren Z, Zhu QB, Huang ML, Swaab DF, Bao AM*. Aromatase changes in depression: a postmortem and animal experimental study. Psychoneuroendocrinology. 2017 Mar;77:56-62.
Zhu QB, Unmehopa U, Bossers K, Hu YT, Verwer R, Balesar R, Zhao J, Bao AM*, Swaab D. MicroRNA-132 and early growth response-1 in Nucleus Basalis of Meynert during the course of Alzheimer’s disease. Brain. 2016 Mar;139(Pt 3):908-21.
Wu JL, Yu SY, Wu SH, Bao AM*. A sensitive and practical RP-HPLC-FLD for determination of the low neuroactive amino acid levels in body fluids and its application in depression. Neurosci Lett. 2016 Mar 11;616:32-7.
Lu J, Wu XY, Zhu QB, Li J, Shi LG, Wu JL, Zhang QJ, Huang ML, Bao AM*. Sex differences in the stress response in SD rats. Behav Brain Res 284 (2015) :231-237.
Wu XY, Hu YT, Guo L, Lu J, Zhu QB, Yu E, Wu JL, Shi LG, Huang ML, Bao AM*. Effect of pentobarbital and isoflurane on acute stress response in rat. Physiol Behav. 2015 (145):118-21.
Shan L, Bao AM*, Swaab DF. The human histaminergic system in neuropsychiatric disorders. Trends Neurosci. 2015 Jan 6. March 2015, Vol. 38, No. 3 167-177.
Yan XX, Ma C, Bao AM, Wang XM, Gai WP. Brain banking as a cornerstone of neuroscience in China. Lancet Neurol. 2015 Feb;14(2):136. doi: 10.1016/S1474-4422(14)70259-5.
Lu YR, Fu XY, Shi LG, Jiang Y, Wu JL, Weng XJ, Wang ZP, Wu XY, Lin Z, Liu WB, Li HC, Luo JH and Bao AM*. Decreased plasma neuroactive amino acids and increased nitric oxide levels in melancholic major depressive disorder. BMC Psychiatry 2014, 14:123 doi:10.1186/1471-244X-14-123.
Gao SF, Lu YR, Shi LG, Wu XY, Sun B, Fu XY, Luo JH, Bao AM*. Nitric oxide synthase and nitric oxide alterations in chronically stressed rats: a model for nitric oxide in major depressive disorder. Psychoneuroendocrinology. 2014 Sep; 47:136-40.
Shan L, Qi XR, Balesar R, Swaab DF, Bao AM*. Unaltered histaminergic system in depression: a postmortem study. J Affect Disord. 2013 Apr 5;146(2):220-223.
Shan L, Swaab DF, Bao AM*. Neuronal histaminergic system in aging and age-related neurodegenerative disorders. Exp Gerontol. 2013 Jul; 48(7):603-607.
Gao SF, Klomp A, Wu JL, Swaab DF, Bao AM*. Reduced GAD65/67 immunoreactivity in the hypothalamic paraventricular nucleus in depression. J Affect Disord. 2013 Jan 9; 149(1–3): 422–425.
Gao SF, Qi XR, Zhao J, Balesar R, Bao AM*, Swaab DF. Decreased nNOS expression in anterior cingulate cortex in depression. Cereb Cortex. 2013 Dec;23(12):2956-64.
Wang ZP, Wu JL, Wu SH, Bao AM*. High-performance liquid chromatographic determination of histamine in biological samples: the cerebrospinal fluid challenge-A review. Analytica Chimica Acta 774 (2013) 1-10.
Zhao J, Bao AM, Qi XR, Kamphuis W, Luchetti S, Lou JS, Swaab DF. Gene expression of GABA and glutamate pathway markers in the prefrontal cortex of non-suicidal elderly depressed patients. J Affect Disord. 2012 May; 138(3): 494-502.
Swaab DF, Bao AM, Garcia-Falgueras A, Hofman MA, Ishunina1 TA. Sex differences in the human forebrain. Human Nervous System 3th edition Eds J. Mai and G. Paximos. Academic Press/Elsevier 2012. Chapter 21, 739-758.
Bao AM*, Ruhé HG, Gao SF, Swaab DF. Neurotransmitters and neuropeptides in depression. In: Handbook of Clinical Neurology. Vol.106, M.J. Aminoff, Boller,F., Swaab, DF, eds. Elsevier Series edts, and Schlaepfer T.E. and Nemeroff C.B. Volume edts, Amsterdam. 2012, 107-136.
Shan L, Hofman MA, van Wamelen DJ, Van Someren EJW, Bao AM*, Swaab DF. Diurnal fluctuation in histidine decarboxylase expression, the rate limiting enzyme for histamine production, and its disorder in neurodegenerative diseases. Sleep 2012, 35(5): 713-715.
Shan L, Bossers K, Unmehopa U, Bao AM*, Swaab DF. Alterations in the histaminergic system in Alzheimer’s disease: a postmortem study. Neurobiol Aging. 2012, 33(11): 2585-2598.
Shan L, Bossers K, Luchetti S, Balesar R, Lethbridge N, Chazot PL, Bao AM*, Swaab DF. Alterations in the histaminergic system in the substantia nigra and striatum of Parkinson's patients: a postmortem study. Neurobiol Aging. 2012, 33(7): 1488.e1–1488.e13.
Shan L, Liu CQ, Balesar R, Hofman MA, Bao AM*, Swaab DF. Neuronal histamine production remains unaltered in Parkinson's disease despite the accumulation of Lewy bodies and Lewy neurites in the tuberomamillary nucleus. Neurobiol Aging. 2012, 33(7): 1343–1344.
Bao AM*, Swaab DF. Sexual differentiation of the human brain: Relation to gender-identity, sexual orientation and neuropsychiatric disorders. Front Neuroendocrinol. 2011 Apr;32(2):214-26.
Van Wamelen DJ, Shan L, Aziz NA, Anink JJ, Bao AM, Roos RA, Swaab DF. Functional Increase of Brain Histaminergic Signaling in Huntington's Disease. Brain Pathol. 2011 Jul;21(4):419-27.
Swaab DF, Bao AM*. (Re-)activation of neurons in aging and dementia: lessons from the hypothalamus. Exp Gerontol. 2011 Feb-Mar; 46(2-3):178-84.
Gao SF, Bao AM*. Corticotropin-releasing hormone, glutamate and γ-aminobutyric acid in depression. Neuroscientist 2011;17(1):124-44.
Liu CQ, Shan L, Balesar R, Luchetti S, Van Heerikhuize JJ, Luo JH, Swaab DF, Bao AM*. A quantitative in situ hybridization protocol for formalin-fixed paraffin-embedded archival postmortem human brain tissue. Methods. 2010 Dec; 52(4):359-66.
Bao AM*, Swaab DF. Corticotrophin-releasing hormone and arginine vasopressin in depression: focus on the human postmortem hypothalamus. Vitamins and Hormones, Volume 81- Hormones of the Limbic System. Edt. Gerry Litwack, Academic Press/Elsevier 2010; 82:339-65.
Chen XN, Meng QY, Bao AM, Swaab DF, Wang GH, Zhou JN. The Involvement of Retinoic Acid Receptor-alpha in Corticotropin-Releasing Hormone Gene Expression and Affective Disorders. Biol Psychiatry. 2009 Nov 1; 66(9):832-9.
Bao AM*, Lucassen PJ, Swaab DF. The Neuroendocrinology of Psychiatric Disorders. Encyclopedic Reference of Neursocience. Edts. M.d.Binder, N.Hirokawa and U.Windhorst. Springer Verlag 2009, 2641-2645.
Bao AM*, Swaab DF. Gender difference in age-related number of corticotropin-releasing hormone-expressing neurons in the human hypothalamic paraventricular nucleus and the role of sex hormones. Neuroendocrinology 2007; 85(1): 27-36.
Tan ZL, Bao AM, Zhao GQ, Liu YJ, Zhou JN. Effect of fluoxetine on circadian rhythm of melatonin in patients with major depressive disorder. Neuro Endocrinol Lett. 2007; 28(1): 28-32.
Tan ZL, Bao AM, Tao M, Liu YJ, Zhou JN. Circadian rhythm of salivary serotonin in patients with major depressive disorder. Neuro Endocrinol Lett. 2007; 28(4): 395-400.
Bao AM, Fischer, DF, Wu YH, Hol EM, Balesar R, Unmehopa UA, Zhou JN, Swaab DF. A direct androgenic involvement in the expression of human corticotropin-releasing hormone. Mol Psychiatry. 2006 Jun; 11(6):567-76.
Wu YH, Zhou JN, Balesar R, Unmehopa U, Bao AM, Jockers R, Van Heerikhuize J, Swaab DF. Distribution of MT1 melatonin receptor immunoreactivity in the human hypothalamus and pituitary gland: colocalization of MT1 with vasopressin, oxytocin, and corticotropin-releasing hormone. J Comp Neurol. 2006; 499(6): 897-910.
Bao AM, Hestiantoro A, van Someren EJW, Swaab DF, Zhou JN. Colocalization of corticotropin-releasing hormone and estrogen receptor-α in the human paraventricular nucleus in depression. Brain. 2005 Jun;128 (Pt 6):1301-13.
Bao AM, Ji YF, van Someren EJW, Hofman MA, Liu RY, Zhou JN. Diurnal rhythms of free estradiol and cortisol during the normal menstrual cycle in women with major depression. Horm Behav. 2004 Feb; 45(2):93-102.
Bao AM, Liu RY, van Someren EJW, Hofman MA, Cao YX, Zhou JN. Diurnal rhythm of free estradiol during the menstrual cycle. Eur J Endocrinol 2003 Feb;148 (2):227-32.
Bao AM, Liu RY, van Someren EJW, Hofman MA, Cao YX, Zhou JN. Changes in diurnal rhythms of free cortisol secretion during the different phases of the menstrual cycle. Sheng Li Xue Bao. 2003; 55(5): 547-53.
Involvement of oxytocin in bipolar disorder: focus on the imbalance between corticotropin releasing hormone and oxytocin. Funding Source: National Natural Science Foundation of China.
Search for the mechanism that makes women more vulnerable for Alzheimer’s disease: focus on the entorhinal cortex change in preclinical Alzheimer stages. Funding Source: National Natural Science Foundation of China.
Interaction between the genetic and environmental risk factors for MDD. Funding Source: Ministry of Science and Technology.
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