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.

Antioxidant and anti‐acetylcholinesterase activities of anchovy (Coilia mystus) protein hydrolysates and their memory‐improving effects on scopolamine‐induced amnesia mice

“…Among them, APH‐8 and APH‐2 exhibited resembled escape latency and error times to the piracetam group. High content of Glu in APH‐8 might be a reason for its good effects on impaired mice brain, which was also found in cerebrolysin (Rockenstein et al ., ), while Asp, Ser and His were reported to be useful in improving cognitive deficits (Butcher et al ., ; Bado et al ., ; Yoshikawa et al ., ).…”

β-Alanine ingestion increases muscle carnosine content and combat specific performance in soldiers

“…Another possible role of carnosine in the brain has suggested that it acts as a reservoir for histidine, which is a precursor for histamine (Zhu et al 2007 ). Decreases in histidine has been demonstrated to reduce brain histamine levels and subsequently increase anxiety-like behaviors (Yoshikawa et al 2014 ), reduce cognitive function (Dai et al 2007 ) and contribute to stress and depression (Yanai et al 1998 ). When histamine levels are elevated levels of anxiety appear to be reduced (Endou et al 2001 ), and memory task capability appears to be maintained (Benetti and Izquierdo 2013 ).…”

Histidine in Health and Disease: Metabolism, Physiological Importance, and Use as a Supplement

“…According to several studies, dietary HIS affects histamine concentrations in immune cells, the stomach, and the brain [58][59][60][61]. Altered function of the immune system, allergic reactions, and/or peptic ulcers have not been reported after HIS administration.…”

“…Several studies have reported an anorectic effect of HIS administration [65][66][67][68] and HIS-enriched diet [62][63][64]. Insufficient HIS intake reduces the brain histamine content and is associated with anxiety-like behaviors in mice [61].…”