Abstract

Given that the spinal cord is capable of learning sensorimotor tasks and that dietary interventions can influence learning involving supraspinal centers, we asked whether the presence of omega-3 fatty acid docosahexaenoic acid (DHA) and the curry spice curcumin (Cur) by themselves or in combination with voluntary exercise could affect spinal cord learning in adult spinal mice. Using an instrumental learning paradigm to assess spinal learning we observed that mice fed a diet containing DHA/Cur performed better in the spinal learning paradigm than mice fed a diet deficient in DHA/Cur. The enhanced performance was accompanied by increases in the mRNA levels of molecular markers of learning, i.e., BDNF, CREB, CaMKII, and syntaxin 3. Concurrent exposure to exercise was complementary to the dietary treatment effects on spinal learning. The diet containing DHA/Cur resulted in higher levels of DHA and lower levels of omega-6 fatty acid arachidonic acid (AA) in the spinal cord than the diet deficient in DHA/Cur. The level of spinal learning was inversely related to the ratio of AA∶DHA. These results emphasize the capacity of select dietary factors and exercise to foster spinal cord learning. Given the non-invasiveness and safety of the modulation of diet and exercise, these interventions should be considered in light of their potential to enhance relearning of sensorimotor tasks during rehabilitative training paradigms after a spinal cord injury.

Highlights

  • Recent evidence indicates that select dietary factors such as docosahexaenoic acid (DHA) can improve learning in the brain by acting on molecular systems involved with synaptic plasticity [1,2]

  • Given that brainderived neurotrophic factor (BDNF) levels are modulated with DHA, curcumin, and exercise, we have focused on molecular systems related to the action of BDNF on synaptic plasticity, such as calcium/calmodulin activated protein kinase II (CaMKII), the gene transcription factor cAMP-response element binding protein (CREB), and syntaxin 3

  • The mRNA levels of BDNF (Fig. 2A), CaMKII (Fig. 2C), CREB (Fig. 2E), and syntaxin 3 (Fig. 2G) were higher in both groups receiving DHA/Cur than in both CtrlDiet groups except that there was no difference in the levels of CaMKII, CREB, or syntaxin 3 mRNA in the CtrlDiet+Ex and DHA/Cur+Sed groups

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Summary

Introduction

Recent evidence indicates that select dietary factors such as docosahexaenoic acid (DHA) can improve learning in the brain by acting on molecular systems involved with synaptic plasticity [1,2]. DHA has been shown to normalize levels of brainderived neurotrophic factor (BDNF), reduce oxidative damage, and counteract learning disabilities in animal models of brain trauma [3]. DHA has been shown to improve locomotor recovery and decrease cellular damage after spinal cord injury. Intravenous acute DHA injection combined with dietary supplementation of DHA after a spinal cord compression injury in adult rats decreased the amount of apoptotic cell death and white matter degradation [5]. Curcumin supplementation has been shown to reduce cognitive [8,9] and locomotor deficits [10,11] via normalizing levels of BDNF in rodents with brain trauma

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