Chiou Lih-Chu 邱麗珠 – NTU Neuroscience

邱麗珠

Lih-Chu Chiou

Lab Introduction & Major Research Interests

Trained as an electrophysiologist, I established my laboratory in 1999 by employing electrophysiological approaches in brain slices containing the periaqueductal gray (PAG) to characterize pharmacologically several nociceptin receptor ligands for years. Recently, we revealed an opioid-independent antinociceptive mechanism mediated by orexin-initiated eCB signaling in the PAG. This mechanism can contribute to the phenomenon of stress-induced analgesia, and surprisingly also to acupuncture analgesia via median nerve stimulation. Insterestingly, this signaling also exists in the ventral tegmental area, and contributes to stress-induced extinguished cocaine seeking. Besides, a drug development project initiated in 2008 by a clinical case where a local herb effectively alleviated intractable motor tics. From this herb, we identified an active constituent, hispidulin that mainly acted as a positive allosteric modulator (PAM) of the α6 subunit-containing GABAA receptors (α6GABAARs). Later, the reports of α6GABAAR-selective pyrazoloquinolinones developed by University of Wisconsin Milwaukee and Medical University of Vienna prompted me to initiate an international drug development team aiming to develop α6GABAAR-slective PAMs as the first-in-class novel therapy for neuropsychiatric disorders, migraine, orofacial pain and essential tremor.

Recent Representative Publication ( * corresponding author)

1. Mouri A, Lee HJ, Mamiya T, Aoyama Y, Matsumoto Y, Kubota H, Huang WJ, Chiou LC and Nabeshima T (2020) Hispidulin attenuates the social withdrawal in isolated disrupted-in-schizophrenia-1 mutant and chronic phencyclidine -treated mice. Br J Pharmacol Mar. 4. DOI: 10.1111/bph.15043.

2. Chen YH, Lee HJ, Lee MT, Wu YT, Lee YH, Hwang LL, Hung MS, Zimmer A, Mackie K and Chiou LC (2018) Median nerve stimulation induces analgesia via orexin-initiated endocannabinoid disinhibition in the periaqueductal gray. Proc Natl Acad Sci USA 115 (45): E10720-E10729.

3. Fan PC, Huang P, Sieghart W, Ernst M, Knutson DE, Cook J and Chiou LC (2018) Alpha6 subunit-containing GABAA receptors: Novel targets for migraine therapy. Neuropharmacology 140:1-13.

4. Chiou LC, Lee HJ, Ernst M, Huang WJ, Chou JF, Chen HL, Mouri A, Chen LG, Treven M, Mamiya T, Fan PC, Knutson DE, Witzigmann C, Cook J, Sieghart W and Nabeshima T. (2018) Cerebellar subunit-containing GABAA receptors: A novel therapeutic target for disrupted prepulse inhibition in neuropsychiatric disorders. Br J Pharmacol 175(12):2414-2427.

5. Tung LW, Lu GL, Lee YH, Yu L, Lee HJ, Leishman E, Bradshaw H, Hwang LL, Hung MS, Mackie K, Zimmer A and Chiou LC (2016) Orexins contribute to restraint stress-induced cocaine relapse by endocannabinoid-mediated disinhibition of dopaminergic neurons. Nat Commun 7:12199.

6. Ho YC, Cheng JK, Chiou LC (2015). Impairment of adenylyl cyclase-mediated glutamatergic synaptic plasticity in the periaqueductal gray in a rat model of neuropathic pain. J Physiol 593.13:2955-2973.

7. Ho YC, Cheng JK and Chiou LC (2013) Hypofunction of glutamatergic neurotransmission in the periaqueductal gray contributes to nerve injury-induced neuropathic pain. J Neurosci 33:7825-7836.

8. Ho YC, Lee HJ, Tung LW, Liao YY, Fu SY, Teng SF, Liao HT, Mackie K and Chiou LC (2011) Activation of orexin 1 receptors in the periaqueductal gray of male rats leads to antinociception via retrograde endocannabinoid (2-arachidonoylglycerol)-induced disinhibition. J Neurosci 31:14600-10.

9. Liao HT, Lee HJ, Ho YC and Chiou LC (2011) Capsaicin in the periaqueductal gray induces analgesia via metabotropic glutamate receptor-mediated endocannabinoid retrograde disinhibition. Br J Pharmacol 163:330-45.

10. Chiou LC, Liao YY, Fan PC, Kuo PH, Wang CH, Riemer C and Prinssen EP (2007) Nociceptin/orphanin FQ peptide receptors: pharmacology and clinical implications. Curr Drug Targets 8:117-35.