Humanin Does Not Protect Against STZ-Induced Spatial Memory Impairment.

[Gly14]-Humanin (HNG) is a 24-amino acid peptide which was first identified in the brains of patients diagnosed with Alzheimer's disease (AD). In this region, some neurons were protected against cell damage occurring in this disease. Further studies suggested a neuroprotective role for humanin against Aβ and some other insults. Intraventricularly administered streptozotocin (STZ) disrupts insulin signaling pathway which leads to behavioral and biochemical changes resemble to early signs of AD; therefore, STZ model has been proposed as a model for sporadic Alzheimer's disease (sAD). Regarding the reported beneficial effects of humanin in AD, this study was aimed to investigate if this peptide prevents spatial memory and hippocampal PI3/Akt signaling impairment induced by centrally injected STZ. Adult male Sprague-Dawely rats weighting 250-300 g were used, and cannuls were implanted bilaterally into lateral ventricles. STZ was administered on days 1 and 3 (3 mg/kg), and humanin (0.01, 0.05, 0.1, and 1 nmol) or saline were injected from day 4 and continued till day 14. The animal's learning and memory capability was assessed on days 15-18 using Morris water maze. After complement of behavioral studies, the hippocampi were isolated, and the level of phosphorylated Akt (pAkt) was assessed through Western blot analysis. The results showed that STZ significantly impaired spatial memory, and humanin in a wide range of doses (0.01, 0.05, 0.1, and 1 nmol) failed to restore STZ-induced deficit. It was also revealed that humanin was not efficient in restoring pAkt disruption. It seems that humanin is not capable in restoring memory deterioration that resulted from insulin signaling disruption.