Oral Supplementation of L-Carnosine Attenuates Acute-Stress-Induced Corticosterone Release and Mitigates Anxiety in CD157 Knockout Mice

Abstract

Corticosterone, an end product of the hypothalamic-pituitary-adrenal (HPA) axis, is a crucial stress hormone. A dysregulated HPA axis and corticosterone release play pivotal roles in the onset and persistence of symptoms of stress-related psychiatric disorders, such as anxiety. The intake of nutrients, probiotics, and prebiotic supplements decreases blood corticosterone levels. The dipeptide L-carnosine is composed of beta-alanine and L-histidine and is commercially available as a nutritional supplement for recovery from fatigue. L-carnosine is involved in stress-induced corticosterone responses and anxiety behaviors in rodents. Here, we assessed the effect of L-carnosine in CD157 knockout (KO) mice, a murine model of autism spectrum disorder (ASD). The uptake of L-carnosine suppressed the increase in plasma corticosterone levels in response to acute stress and attenuated anxiety-like behaviors in CD157 KO mice. These results suggest that L-carnosine supplementation may relieve anxiety by suppressing excessive stress responses in individuals with ASD.

Keywords: CD157; L-carnosine; anxiety; autism spectrum disorder; corticosterone; stress.

Figure 1

Plasma corticosterone level after acute stress in WT and CD157KO group with or without treatment of carnosine. (a) The plasma corticosterone without any stress as control. (b) The plasma corticosterone level after 6 min of forced swimming. (c) The plasma corticosterone levels after 6 min of restrained stress. Numbers of animals are shown in bars. Bars are represented in median and interquartile ranges in each group. * p ≤ 0.05, ** p ≤ 0.01.

Figure 2

Elevated plus maze test. (a) Numbers of entries in the open arms. (b) Time in the open arm or the closed arm. Numbers of animals are shown in bars. Bars are represented in median and interquartile ranges in each group. * p ≤ 0.05. ** p ≤ 0.01. n.s.: not significant.