Ocular nerve growth factor administration counteracts the impairment of neural precursor cell viability and differentiation in the brain subventricular area of rats with streptozotocin-induced diabetes.
The ocular administration of nerve growth factor (NGF) as eye drops (oNGF) has been shown to exert protective effects in forebrain-injured animal models, including adult diabetes induced by a single injection of streptozotocin (STZ) (60 mg/kg body weight). This type 1 diabetes model was used in this study to investigate whether oNGF might extend its actions on neuronal precursors localised in the subventricular zone (SVZ). NGF or saline was administrated as eye drops twice daily for 2 weeks in rats with STZ-induced diabetes and healthy control rats. The expression of mature and precursor NGF and the NGF receptors, tropomyosin-related kinase A and neurotrophin receptor p75, and the levels of DNA fragmentation were analysed by ELISA and western blotting. Incorporation of bromodeoxyuridine was used to trace newly formed cells. Nestin, polysialylated neuronal cell adhesion molecule (PSA-NCAM), doublecortin (DCX) and glial fibrillary acidic protein antibodies were used to identify the SVZ cells by confocal microscopy. It was found that oNGF counteracts the STZ-induced cell death and the alteration of mature/pro-NGF expression in the SVZ. It also affects the survival and differentiation of SVZ progenitors. In particular, oNGF counteracts the reduction in the number of cells expressing PSA-NCAM/DCX (neuroblast type A cells) and the related reductions in the number and distribution of nestin/DCX-positive cells (C-type cells), or glia-committed cells (type B cells), observed in the SVZ of diabetic rats. These findings show that oNGF treatment counteracts the effect of type 1 diabetes on neuronal precursors in the SVZ, and further support the neuroprotective and reparative role of oNGF in the brain.
Institute of Cell Biology and Neurobiology, National Research Council (CNR), Via del Fosso di Fiorano, 64 (00143), Rome, Italy.
Paola
P
Tirassa
Mattia
M
Maccarone
Valentina
V
Carito
Sara
S
De Nicolò
Marco
M
Fiore
D000818:Animals; D002470:Cell Survival; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003930:Diabetic Retinopathy / Q000188:drug therapy*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D020547:Lateral Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D055495:Neurogenesis; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism
C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D064231:Nestin; D019006:Neural Cell Adhesion Molecules; D009479:Neuropeptides; D020800:Receptor, Nerve Growth Factor; D020932:Nerve Growth Factor; D011494:Protein Kinases
brain pathology; collyrium; neurogenesis; neuroprotection; neurotrophins