Ocular Nerve Growth Factor Administration Modulates Brain-derived Neurotrophic Factor Signaling in Prefrontal Cortex of Healthy and Diabetic Rats.

Aims Nerve growth factor ( NGF) eyedrops (ed- NGF) activate brain neurons, stimulate growth factors, including brain-derived neurotrophic factor ( BDNF), and exert neuroprotection in the forebrain of streptozotocin-induced diabetic rats ( STZ rats). In this study, the effects of ed- NGF on BDNF signaling in the prefrontal cortex ( PFC) were explored in healthy and STZ-diabetic rats, in which cortical neuronal and axonal loss, and altered circulating BDNF associated with depressive phenotype are also described. Methods STZ and healthy ( CTR) adult rats received ed- NGF twice a day for 2 weeks. Depressive phenotype was identified by force swimming test ( FST). Proteins extracted from PFC were processed for ELISA and Western blot analyses to measure the expression of BDNF, pro BDNF, and their receptors and intracellular signals. Results ed- NGF treatment modulates BDNF pathway in PFC and normalizes the STZ-induced BDNF alterations by stimulating TRK-mediated survival mechanism. A decreased latency in FST was also found in STZ rats, while no change was observed comparing CTR + NGF and STZ + NGF with CTR. Conclusion The present data confirm the capacity of ed- NGF treatment to affect brain neurons and lead to brain damage recovery by activating protective and remodeling pathways triggered by BDNF. We suggest that the ed- NGF-induced changes in BDNF signaling might influence the manifestation of depressive phenotype in diabetic rats. [ABSTRACT FROM AUTHOR]