[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.

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Background & aim: Steroid production has been reported in the asexual tissues of the nervous system. Stimulants are in the normal activity, function and function of the nervous system. Identifying the conduction pathways involved in glucocorticoids and enabling brain parenchymal cells can offset the balance in the active nervous system at old ages when the body is depleted. Therefore, in this study, by increasing the activity of sonic hedgehog (SHH) pathway attempted by purmorphamine and its capacity by Gant 61, the effect of this pathway on steroid process in culture medium of glial neurons is evaluated. Methods:The present experimental study was conducted in 2021. First, neuronal stem cells were obtained from the cortex of a 14-day-old embryonic mice by standard methods. Survival of neuronal stem cells after treatment with 5 μM pregnenolone with different concentrations of purmorphamine (1,2,5, 10 and 20) and Gant 61 was performed by MTT method. Then the cells were placed in a differentiation medium and after treatment with different concentrations and 5-day incubation, the surface of the cells was removed from the cell culture medium and the amount of testosterone and estrogen were measured by ELISA and HPLC. Data were analyzed using ANOVA statistical test using graph pad software. Results:The survival data of the groups indicated an increase in survival after treatment with purmorphamine (114.3) compared to the Gant 61 group (63.7 Pg) (p≤0.5). Progesterone data in the supernatant of glial neurons showed that purmorphamine groups (287.2 Pg) had a significant increase compared to control (88.28) and Gant 61 (40.5 Pg) groups (p≤ 0.001). Also, testosterone data show that purmorphamine groups (73.8 Pg) in both ELISA and HPLC methods have a significant increase compared to the control (153.8 Pg) and Gant61 (52.92 Pg) groups (p≤ 0.0001). Also, pregnenolone group (236.5 Pg) showed a significant increase compared to Gant61 (40.5 Pg) group (p≤ 0.05). Analysis of estrogen data by HPLC method showed that there was a significant increase in estrogen production in the purmorphamine groups (331.2 Pg) compared to the control (42.11 Pg) and Gant61 (42.11 Pg) groups (p≤ 0.0001). Conclusion:The data from this study indicated that the induction of the shh pathway by purrmorphamine increased the production of steroid hormones (estrogen-progesterone and testosterone) by glial-neuronal differentiating cells, which inhibition of this pathway had the opposite effect. The present study concluded that induction of the shh pathway can lead to the production of steroids.