J Nutr. 2014 Oct;144(10):1637-41. doi: 10.3945/jn.114.196105. Epub 2014 Jul 23.

Insufficient intake of L-histidine reduces brain histamine and causes anxiety-like behaviors in male mice.

Yoshikawa T1, Nakamura T1, Shibakusa T2, Sugita M2, Naganuma F1, Iida T1, Miura Y1, Mohsen A1, Harada R1, Yanai K3.

• 1Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan; and.
• 2Institute for Innovation, Ajinomoto Co., Inc., Kawasaki, Japan.
• 3Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan; and yanai@med.tohoku.ac.jp.

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.

© 2014 American Society for Nutrition.

PMID:  25056690