Both the neuronal and inducible isoforms contribute to upregulation of retinal nitric oxide synthase activity by brain-derived neurotrophic factor

1999 | journal article; research paper. A publication with affiliation to the University of Göttingen.

Jump to:Cite & Linked | Documents & Media | Details | Version history

Cite this publication

​Both the neuronal and inducible isoforms contribute to upregulation of retinal nitric oxide synthase activity by brain-derived neurotrophic factor​
Klocker, N.; Kermer, P. ; Gleichmann, M.; Weller, M. & Bähr, M. ​ (1999) 
The Journal of neuroscience19(19) pp. 8517​-8527​.​

Documents & Media

License

GRO License GRO License

Details

Authors
Klocker, N.; Kermer, Pawel ; Gleichmann, M.; Weller, M; Bähr, Mathias 
Abstract
Although neurotrophins are best known for their trophic functions, growing evidence suggests that neurotrophins can also be neurotoxic, for instance by enhancing excitotoxic insults. We have shown recently that brain-derived neurotrophic factor (BDNF) limits its neuroprotective action on axotomized rat retinal ganglion cells (RGCs) by upregulating nitric oxide synthase (NOS) activity (Klocker et al., 1998). The aim of the present study was to investigate this interaction of BDNF and NOS in the lesioned adult rat retina in more detail. We used NOS immunohistochemistry and NADPH-diaphorase (NADPH-d) reaction to characterize morphologically retinal NOS expression and activity. Using reverse transcription-PCR and Western blot analysis, we were able to identify the NOS isoforms being regulated. Six days after optic nerve lesion, we observed an increase in neuronal NOS (NOS-I) mRNA and protein expression in the inner retina. This did not lead to a marked increase in overall retinal NOS activity. Only RGC axons displayed strong de novo NADPH-d reactivity. In contrast, intraocular injection of BDNF resulted in a marked upregulation of NOS activity in NOS-I-immunoreactive structures, leaving the level of NOS-I expression unchanged. In addition, an induction of inducible NOS (NOS-II) was found after BDNF treatment. We identified microglial cells increasing in number and being activated by BDNF, which could serve as the cellular source of NOS-II. In summary, our data suggest that BDNF upregulates retinal NOS activity by both a post-translational regulation of NOS-I activity and an induction of NOS-II. These findings might be useful for developing pharmacological strategies to improve BDNF-mediated neuroprotection.
Issue Date
1999
Publisher
Soc Neuroscience
Journal
The Journal of neuroscience 
ISSN
0270-6474

Reference

Citations