title: Effects of brain-derived neurotrophic factor on the development of NADPH-diaphorase/nitric oxide synthase-positive amacrine cells in the rodent retina.
abstract: Amacrine neurons expressing nitric oxide synthase (NOS) contain brain-derived neurotrophic factor (BDNF) receptors and respond to exogenous BDNF [Klöcker, N., Cellerino, A. & Bähr, M. (1998) J. Neurosci., 18, 1038-1046]. We analysed the effects of BDNF on the development of neurons which express NOS in the mouse and rat retina. Rat pups received a total of three intraocular injections of BDNF at intervals of 48 h, starting at postnatal day 16 (P16), and were killed at P22. The retinas were stained for NADPH-diaphorase, a histological marker of NOS. NOS-expressing neurons were found in both the inner nuclear layer (INL) and the ganglion cell layer (GCL). Two classes of NOS-expressing neurons, type I and type II, had already been distinguished in the INL [Koistinaho, J. & Sagar, S.M. (1995) In Osborne, N.N. & Chader, G.J. (eds), Progress in Retinal and Eye Research, Vol. 15. Oxford University Press, pp. 69-87] and a third one in the GCL. Up-regulation of NADPH-diaphorase activity was observed after BDNF treatment. The number of type I neurons remained stable, whereas the number of type II neurons and NOS-positive neurons in the GCL increased significantly (P < 0.001). Type I and type II neurons were significantly larger in BDNF-treated retinas. Double-labelling experiments revealed that BDNF induces NADPH-diaphorase in dopaminergic neurons and amacrine cells displaced to the GCL, but not in retinal ganglion cells. In mice homozygous for a null mutation of the bdnf gene, the intensity of NADPH-diaphorase labelling in both somata and processes was reduced, but the number of labelled neurons was not dramatically reduced. These findings indicate that BDNF regulates the neurotransmitter phenotype of NOS-expressing amacrine neurons under physiological conditions, but is not required for their survival.
authors.affiliation: Department of Pathophysiology of Vision and Neuroophthalmology, Division of Experimental Ophthalmology, University Eye Hospital, Tübingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Cellerino
authors.forename: B A
authors.initials: BA
authors.lastname: Arango-González
authors.forename: K
authors.initials: K
authors.lastname: Kohler
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D011914:Rats, Inbred BN; D011994:Recombinant Proteins / Q000494:pharmacology; D012160:Retina / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000201:enzymology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C496322:Nos1 protein, rat; D009252:NADPH Dehydrogenase; D004298:Dopamine