Moxibustion upregulates hippocampal progranulin expression

Abstract

In China, moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome, but its mechanisms are largely unknown. More recently, the focus has been on the wealth of information supporting stress as a factor in chronic fatigue syndrome, and largely concerns dysregulation in the stress-related hypothalamic-pituitary-adrenal axis. In the present study, we aimed to determine the effect of moxibustion on behavioral symptoms in chronic fatigue syndrome rats and examine possible mechanisms. Rats were subjected to a combination of chronic restraint stress and forced swimming to induce chronic fatigue syndrome. The acupoints Guanyuan (CV4) and Zusanli (ST36, bilateral) were simultaneously administered moxibustion. Untreated chronic fatigue syndrome rats and normal rats were used as controls. Results from the forced swimming test, open field test, tail suspension test, real-time PCR, enzyme-linked immunosorbent assay, and western blot assay showed that moxibustion treatment decreased mRNA expression of corticotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone and corticosterone levels in plasma, and markedly increased progranulin mRNA and protein expression in the hippocampus. These findings suggest that moxibustion may relieve the behavioral symptoms of chronic fatigue syndrome, at least in part, by modulating the hypothalamic-pituitary-adrenal axis and upregulating hippocampal progranulin.

Keywords: adrenocorticotropic hormone; behavioral symptoms; chronic fatigue syndrome; corticosterone; corticotrophin-releasing hormone; hippocampus; hypothalamic-pituitary-adrenal axis; moxibustion; nerve regeneration; neural regeneration; progranulin; traditional Chinese medicine.

Figure 1

Moxibustion at the Zusanli (CV4) and Guanyuan (ST36) acupoints.

Figure 2

Behavioral performance of CFS rats after moxibustion treatment in the forced swimming test, open field test, and tail suspension test. Data are presented as the mean ± SEM (n = 8 per group; one-way analysis of variance followed by the least significant difference post hoc test). (A) Maximal swimming time in the forced swimming test. (B) Locomotion frequency (number of total squares crossed) in the open field test. (C) Rearing frequency (rat stood upright on its hind legs) in the open field test. (D) Immobile time (lack of all movement) in the tail suspension test. **P < 0.01, vs. normal; ##P < 0.01, vs. CFS. MX: Moxibustion; CFS: chronic fatigue syndrome.

Figure 3

Moxibustion modulated the hypothalamic-pituitary-adrenal axis of CFS rats. Data are presented as the mean ± SEM (n = 8 per group; one-way analysis of variance followed by the least significant difference post hoc test). (A) CRH mRNA expression in the hypothalamus was semi-quantified by real-time PCR. (B, C) ACTH (B) and CORT (C) concentration in plasma was detected by enzyme-linked immunosorbent assay. **P < 0.01, vs. normal; ##P < 0.01, vs. CFS. CFS: Chronic fatigue syndrome; CRH: corticotrophin-releasing hormone; ACTH: adrenocorticotropic hormone; CORT: corticosterone; MX: moxibustion.

Figure 4

Moxibustion modulated progranulin mRNA and protein expression in the hippocampus of CFS rats. β-Actin served as a loading control. Data are presented as the mean ± SEM (n = 8 per group; one-way analysis of variance followed by the least significant difference post hoc test). (A) Progranulin protein expression (progranulin/β-actin gray values) in the hippocampus was detected by western blot assay. (B) Progranulin mRNA expression (2^–ΔΔCt) in the hippocampus was semi-quantified by real-time PCR. *P < 0.05, **P < 0.01, vs. normal; ##P < 0.01, vs. CFS. MX: Moxibustion; CFS: chronic fatigue syndrome.