Dipeptide mimetic of BDNF ameliorates motor dysfunction and striatal apoptosis in 6-OHDA-induced Parkinson’s rat model: Considering Akt and MAPKs signaling

Abstract

Parkinson’s disease (PD) is a progressive and debilitating neurodegenerative disorder associated with motor and non-motor complaints. Dysregulation of neurotrophic factors and related signaling cascades have been reported to be common events in PD which is accompanied by dopaminergic (DA) neuron demise. However, the restoration of neurotrophic factors has several limitations. Bis-(N-monosuccinyl-L-methionyl-L-serine) heptamethylenediamide (BHME) is a dipeptide mimetic of brain-derived neurotrophic factor (BDNF) with reported anti-oxidant and neuroprotective effects in several experimental models. The current study has investigated the effect of BHME on 6-hydroxydopamine (6-OHDA)-caused motor anomalies in Wistar rats. In this regard, rats were treated daily with BHME (0.1 or 1 mg/kg) 1 h after 6-OHDA-caused damage until the twelfth day. Afterwards, motor behavior and DA neuron survival were evaluated via behavioral tests and immunohistochemistry (IHC) staining, respectively. Moreover, the activity of Akt, mitogen-activated protein kinases (MAPKs) family, and Bax/Bcl-2 ratio were evaluated by Western blotting. Our results indicated that BHME prevents motor dysfunction and DA cell death following 6-OHDA injection, and this improvement was in parallel with an enhancement in Akt activity, decrement of P38 phosphorylation, along with a reduction in Bax/Bcl-2 ratio. In conclusion, our findings indicated that BHME, as a mimetic of BDNF, can be considered for further research and is a promising therapeutic agent for PD therapy.