title: Ocular Nerve Growth Factor Administration Modulates Brain-derived Neurotrophic Factor Signaling in Prefrontal Cortex of Healthy and Diabetic Rats.
abstract: OBJECTIVE
  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, proBDNF, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Research Council (CNR), Institute of Cell Biology & Neurobiology, Rome, Italy.|Department of Science, LIME, University Roma Tre, Rome, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Rosso
authors.affiliation: National Research Council (CNR), Institute of Cell Biology & Neurobiology, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: De Nicolò
authors.affiliation: National Research Council (CNR), Institute of Cell Biology & Neurobiology, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Carito
authors.affiliation: National Research Council (CNR), Institute of Cell Biology & Neurobiology, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Fiore
authors.affiliation: Department of Medical-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, Rome, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Iannitelli
authors.affiliation: Department of Science, LIME, University Roma Tre, Rome, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Moreno
authors.affiliation: National Research Council (CNR), Institute of Cell Biology & Neurobiology, Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Tirassa
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D003866:Depressive Disorder / Q000209:etiology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D020932:Nerve Growth Factor / Q000008:administration & dosage* / Q000494:pharmacology*; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012794:Sialic Acids / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013311:Streptozocin / Q000633:toxicity; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D039842:Neural Cell Adhesion Molecule L1; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D013311:Streptozocin; D020932:Nerve Growth Factor; D053148:Caspase 3; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D010751:Phosphopyruvate Hydratase
keywords: Depression; Diabetes; NGF eyedrops; TrkB; p75NTR