Expression of Neurotrophin-3 and trkC following Focal Cerebral Ischemia in Adult Rat Brain with Treadmill Exercise

Abstract

Neurotrophin-3 (NT-3) is a neurotrophic factor that mainly binds to the tyrosine kinase C (trkC) receptor. NT-3 has been shown to have neuroprotective effects in focal cerebral ischemia. Exercise also has ability to induce functional recovery in focal cerebral ischemia. However, the relationship between NT-3, its receptor trkC, and exercise has not been revealed. In this study, we assessed the expressions of NT-3 and trkC in focal cerebral ischemia. We also assessed the expression of NT-3 and trkC with treadmill exercise in focal cerebral ischemia. The results showed that, in a permanent middle cerebral artery occlusion rat model, exercise increased NT-3 and trkC expression. However, the patterns of expression of NT-3 and trkC at different time points varied. These results suggest that exercise-induced functional recovery in focal cerebral ischemia was related to NT-3 and trkC, but the role on times of NT-3 and trkC differed, although trkC is the receptor kinase for NT-3.

Figure 1

Expression profile of NT-3. (A) There are two forms of NT-3, dimer (40 kDa) and monomer (21 kDa). Exercise in the sham group increased immunoreactivities of the monomer. Exercise in ischemia increased the monomer in the contralateral hemisphere (contra). (B) In the ischemia-nonexercise group, expression of the NT-3 dimer protein decreased from postinfarct day 9 to postinfarct day 23 in the contralateral region. In the ipsilateral region, expression of NT-3 dimer protein was decreased at postinfarct day 9 and then increased at postinfarct day 23. However, in the ischemia-exercise group, expression of the NT-3 dimer protein was decreased at postinfarct day 16 and then increased at postinfarct day 23. (C) The expression of NT-3 dimer protein increased along with severities II and III in the ischemia-nonexercise group. However, expression of NT-3 dimer decreased in the ischemia-exercise group. (D) (a) Immunoreactivity decreased in the core of the infracted region. In contrast, staining increased around the ischemic area. (b) Exercise decreased this contrasting effect. (a') and (b') are magnificent figures of (a) and (b) each. ■ = 25 μm (^∗p < 0.05).

Figure 2

trkC expression profile. (A) There are two forms: full-length (140 kDa) and truncated (90–95 kDa). Ischemia increased both forms, while exercise increased both forms of protein in the bilateral hemispheres, particularly in the contralateral hemisphere (contra) in the ischemic brain. (B) The maximal expression of the two forms was observed at day 23 in the ischemia group. In the exercise group, the full-length form increased with time in the contralateral region, while the expression of the full-length decreased with time in the ipsilateral region. The truncated form was increased at postinfarct day 23 in the contralateral region. (C) (a) In the sham group, exercise itself increased immunoreactivities in both hemispheres, particularly in the vascular structures. (b) Immunoreactivity also increased in the ischemic region. (c) The immunoreactivities were restricted following exercise. (a'), (b'), and (c') are magnificent figures of (a), (b), and (c) each. ■ = 25 μm (^∗p < 0.05).