PMID- 10493752
OWN - NLM
STAT- MEDLINE
DCOM- 19991014
LR  - 20220310
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 19
IP  - 19
DP  - 1999 Oct 1
TI  - Both the neuronal and inducible isoforms contribute to upregulation of retinal 
      nitric oxide synthase activity by brain-derived neurotrophic factor.
PG  - 8517-27
AB  - 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.
FAU - Klocker, N
AU  - Klocker N
AD  - Department of Neurology, University of Tubingen, 72076 Tubingen, Germany.
FAU - Kermer, P
AU  - Kermer P
FAU - Gleichmann, M
AU  - Gleichmann M
FAU - Weller, M
AU  - Weller M
FAU - Bahr, M
AU  - Bahr M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Messenger)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos1 protein, rat)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
RN  - W8O17SJF3T (Memantine)
SB  - IM
MH  - Animals
MH  - Axotomy
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Female
MH  - Gene Expression Regulation, Enzymologic/drug effects/*physiology
MH  - Immunohistochemistry
MH  - Memantine/pharmacology
MH  - Nerve Fibers/*enzymology/ultrastructure
MH  - Nitric Oxide Synthase/analysis/*genetics
MH  - Nitric Oxide Synthase Type I
MH  - Nitric Oxide Synthase Type II
MH  - Optic Nerve/*physiology
MH  - RNA, Messenger/genetics
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Retina/cytology/*enzymology
MH  - *Transcription, Genetic/drug effects
PMC - PMC6783014
EDAT- 1999/09/24 00:00
MHDA- 1999/09/24 00:01
PMCR- 2000/04/01
CRDT- 1999/09/24 00:00
PHST- 1999/09/24 00:00 [pubmed]
PHST- 1999/09/24 00:01 [medline]
PHST- 1999/09/24 00:00 [entrez]
PHST- 2000/04/01 00:00 [pmc-release]
AID - 3453 [pii]
AID - 10.1523/JNEUROSCI.19-19-08517.1999 [doi]
PST - ppublish
SO  - J Neurosci. 1999 Oct 1;19(19):8517-27. doi: 10.1523/JNEUROSCI.19-19-08517.1999.