title: Insufficient intake of L-histidine reduces brain histamine and causes anxiety-like behaviors in male mice.
abstract: L-histidine is one of the essential amino acids for humans, and it plays a critical role as a component of proteins. L-histidine is also important as a precursor of histamine. Brain histamine is synthesized from L-histidine in the presence of histidine decarboxylase, which is expressed in histamine neurons. In the present study, we aimed to elucidate the importance of dietary L-histidine as a precursor of brain histamine and the histaminergic nervous system. C57BL/6J male mice at 8 wk of age were assigned to 2 different diets for at least 2 wk: the control (Con) diet (5.08 g L-histidine/kg diet) or the low L-histidine diet (LHD) (1.28 g L-histidine/kg diet). We measured the histamine concentration in the brain areas of Con diet-fed mice (Con group) and LHD-fed mice (LHD group). The histamine concentration was significantly lower in the LHD group [Con group vs. LHD group: histamine in cortex (means ± SEs): 13.9 ± 1.25 vs. 9.36 ± 0.549 ng/g tissue; P = 0.002]. Our in vivo microdialysis assays revealed that histamine release stimulated by high K(+) from the hypothalamus in the LHD group was 60% of that in the Con group (P = 0.012). However, the concentrations of other monoamines and their metabolites were not changed by the LHD. The open-field tests showed that the LHD group spent a shorter amount of time in the central zone (87.6 ± 14.1 vs. 50.0 ± 6.03 s/10 min; P = 0.019), and the light/dark box tests demonstrated that the LHD group spent a shorter amount of time in the light box (198 ± 8.19 vs. 162 ± 14.1 s/10 min; P = 0.048), suggesting that the LHD induced anxiety-like behaviors. However, locomotor activity, memory functions, and social interaction did not differ between the 2 groups. The results of the present study demonstrated that insufficient intake of histidine reduced the brain histamine content, leading to anxiety-like behaviors in the mice.
authors: Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Takeo
authors: T
authors: Yoshikawa
authors: Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Tadaho
authors: T
authors: Nakamura
authors: Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
authors: Tetsuro
authors: T
authors: Shibakusa
authors: Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
authors: Mayu
authors: M
authors: Sugita
authors: Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Fumito
authors: F
authors: Naganuma
authors: Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Tomomitsu
authors: T
authors: Iida
authors: Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Yamato
authors: Y
authors: Miura
authors: Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Attayeb
authors: A
authors: Mohsen
authors: Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
authors: Ryuichi
authors: R
authors: Harada
authors: Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan; and yanai@med.tohoku.ac.jp.
authors: Kazuhiko
authors: K
authors: Yanai
mesh_terms: D000818:Animals; D001007:Anxiety / Q000209:etiology / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000378:metabolism; D004032:Diet; D006632:Histamine / Q000378:metabolism*; D006639:Histidine / Q000008:administration & dosage* / Q000172:deficiency; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D009474:Neurons / Q000378:metabolism
chemical_list: D006639:Histidine; D006632:Histamine