Cystamine attenuated behavioral deficiency via increasing the expression of BDNF and activating PI3K/Akt signaling in 2,5-hexanedione intoxicated rats.

Organic solvent-induced neurodegeneration is a severe public health problem which has no effective prevention measures yet. Cystamine stands as a promising neuroprotective agent against many degenerative diseases. In the present study, we investigated the possible protective effects of cystamine against 2,5-hexanedione (2,5-HD) induced peripheral neuropathy. Chronic exposure to 2,5-HD (300 mg kg-1, 6 times per week for 6 weeks) resulted in obvious peripheral nerve damage shown as the elevation of gait scores and the increase of latency in an accelerating rota-rod test. Cystamine (30 mg kg-1 and 60 mg kg-1) co-treatment obviously ameliorated 2,5-HD-induced impairments of the peripheral nervous system. To decipher the underlying mechanisms, we investigated the effects of cystamine on the regulation of brain-derived neurotrophic factor (BDNF) and heat shock protein-70 (Hsp70) expression and the PI3K/Akt signaling pathway. The results revealed that cystamine up-regulated the protein levels of BDNF and Hsp70, accompanied by the activation of the PI3K/Akt pathway in the spinal cord, which might account for the protection of cystamine against 2,5-HD-induced neuropathy.