[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.