Dietary curcumin supplementation counteracts reduction in levels of molecules involved in energy homeostasis after brain trauma

Abstract

Traumatic brain injury (TBI) is followed by an energy crisis that compromises the capacity of the brain to cope with challenges, and often reduces cognitive ability. New research indicates that events that regulate energy homeostasis crucially impact synaptic function and this can compromise the capacity of the brain to respond to challenges during the acute and chronic phases of TBI. The goal of the present study is to determine the influence of the phenolic yellow curry pigment curcumin on molecular systems involved with the monitoring, balance, and transduction of cellular energy, in the hippocampus of animals exposed to mild fluid percussion injury (FPI). Young adult rats were exposed to a regular diet (RD) without or with 500 ppm curcumin (Cur) for four weeks, before an FPI was performed. The rats were assigned to four groups: RD/Sham, Cur/Sham, RD/FPI, and Cur/FPI. We found that FPI decreased the levels of AMP-activated protein kinase (AMPK), ubiquitous mitochondrial creatine kinase (uMtCK) and cytochrome c oxidase II (COX-II) in RD/FPI rats as compared to the RD/sham rats. The curcumin diet counteracted the effects of FPI and elevated the levels of AMPK, uMtCK, COX-II in Cur/FPI rats as compared to RD/sham rats. In addition, in the Cur/sham rats, AMPK and uMtCK increased compared to the RD/sham. Results show the potential of curcumin to regulate molecules involved in energy homeostasis following TBI. These studies may foster a new line of therapeutic treatments for TBI patients by endogenous upregulation of molecules important for functional recovery.

Fig. 1

(A) Ratio of pAMPK/AMPK in rat hippocampus revealed by Western blot analysis in all the groups. (B) Representative Western blots for pAMPK, AMPK and actin from different groups in hippocampus. The ratio of pAMPK/AMPK was significantly reduced after FPI, whereas dietary curcumin (Cur) supplementation significantly increased the ratio of pAMPK/AMPK in TBI rats. The values were converted to percent of RD sham group (mean±SEM). * P<0.05, ANOVA followed by post hoc tests with Bonferroni's comparisons. RD, regular diet. (C, D) Immunohistochemical localization of AMPK distribution in the hippocampus. TBI resulted in reduced immunostaining of AMPK in pyramidal neurons of hippocampus, but dietary Cur could counteract the effect of TBI, preserving the expression of these molecules in hippocampus. Scale bars=100 μm.

Fig. 2

(A–D) Expression of (A) uMtCK, (B) UCP2, (C) COX-II and (D) Sir 2 in rat hippocampus revealed by Western blot analysis. Expression of these molecular systems associated with energy homeostasis was significantly reduced after FPI, whereas dietary curcumin (Cur) supplementation significantly increased their levels in TBI rats. The values were converted to percent of RD sham group (mean±SEM). * P<0.05, ANOVA followed by post hoc tests with Bonferroni's comparisons. RD, regular diet.

Fig. 3

Possible mechanisms underlying the beneficial effects of curcumin dietary supplementation on the injured brain. TBI may lead to disturbances in energy homeostasis and mitochondrial dysfunction resulting in neurodegeneration and altered synaptic plasticity, which could further lead to cognitive dysfunction. On the other hand, the beneficial effect of curcumin dietary supplementation could be due to its ability to restore the energy homeostasis as indicated by levels of molecules like AMPK, uMtCK, UCP2, COX-II and SIR2.