BDNF receptor blockade hinders the beneficial effects of exercise in a rat model of Parkinson's disease.

Physical exercise is known to produce beneficial effects to the nervous system. In most cases, brain-derived neurotrophic factor (BDNF) is involved in such effects. However, little is known on the role of BDNF in exercise-related effects on Parkinson's disease (PD). The aim of this study was to investigate the effects of intermittent treadmill exercise-induced behavioral and histological/neurochemical changes in a rat model of unilateral PD induced by striatal injection of 6-hydroxydopamine (6-OHDA), and the role of BDNF in the exercise effects. Adult male Wistar rats were divided into two main groups: (1) injection of K252a (a blocker of BDNF receptors), and (2) without BDNF receptor blockade. These groups were then subdivided into four groups: control (CLT), sedentary (SED, non-exercised with induction of PD), exercised 3×/week during four weeks before and four weeks after the induction of PD (EXB+EXA), and exercised 3×/week during four weeks after the induction of PD (EXA). One month after 6-OHDA injections, the animals were subjected to rotational behavioral test induced by apomorphine and the brains were collected for immunohistochemistry and immunoblotting assays, in which we measured BDNF and tyrosine hydroxylase (TH) in the substantia nigra pars compacta (SNc) and the striatum (caudate-putamen, CPu). Our results showed a significant reduction of rotational asymmetry induced by apomorphine in the exercised parkinsonian rats. BDNF decreased in the SNc of the SED group, and exercise was able to revert that effect. Exercised groups exhibited reduced damage to the dopaminergic system, detected as a decreased drop of TH levels in SNc and CPu. On the other hand, BDNF blockade was capable of substantially reducing TH expression postlesion, implying enhanced dopaminergic cell loss. Our data revealed that physical exercise is capable of reducing the damage induced by 6-OHDA, and that BDNF receptors are involved in that effect.