TY  - JOUR
PY  - 2017//
TI  - Histamine N-methyltransferase regulates aggression and the sleep-wake cycle
JO  - Scientific reports
A1  - Naganuma, Fumito
A1  - Nakamura, Tadaho
A1  - Yoshikawa, Takeo
A1  - Iida, Tomomitsu
A1  - Miura, Yamato
A1  - Kárpáti, Anikó
A1  - Matsuzawa, Takuro
A1  - Yanai, Atushi
A1  - Mogi, Asuka
A1  - Mochizuki, Takatoshi
A1  - Okamura, Nobuyuki
A1  - Yanai, Kazuhiko
SP  - e15899
EP  - e15899
VL  - 7
IS  - 1
N2  - Histamine is a neurotransmitter that regulates diverse physiological functions including the sleep-wake cycle. Recent studies have reported that histaminergic dysfunction in the brain is associated with neuropsychiatric disorders. Histamine N-methyltransferase (HNMT) is an enzyme expressed in the central nervous system that specifically metabolises histamine; yet, the exact physiological roles of HNMT are unknown. Accordingly, we phenotyped Hnmt knockout mice (KO) to determine the relevance of HNMT to various brain functions. First, we showed that HNMT deficiency enhanced brain histamine concentrations, confirming a role for HNMT in histamine inactivation. Next, we performed comprehensive behavioural testing and determined that KO mice exhibited high aggressive behaviours in the resident-intruder and aggressive biting behaviour tests. High aggression in KO mice was suppressed by treatment with zolantidine, a histamine H2 receptor (H2R) antagonist, indicating that abnormal H2R activation promoted aggression in KO mice. A sleep analysis revealed that KO mice exhibited prolonged bouts of awakening during the light (inactive) period and compensatory sleep during the dark (active) period. Abnormal sleep behaviour was suppressed by treatment with pyrilamine, a H1R antagonist, prior to light period, suggesting that excessive H1R activation led to the dysregulation of sleep-wake cycles in KO mice. These observations inform the physiological roles of HNMT.<p />  <p>Language: en</p>
LA  - en
SN  - 2045-2322
UR  - http://dx.doi.org/10.1038/s41598-017-16019-8
ID  - ref1
ER  -