PMID- 12498910
OWN - NLM
STAT- MEDLINE
DCOM- 20030516
LR  - 20190624
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 458
IP  - 1-2
DP  - 2003 Jan 1
TI  - Protective effects of selegiline and desmethylselegiline against 
      N-methyl-D-aspartate-induced rat retinal damage.
PG  - 81-9
AB  - Selegiline, a therapeutic agent of Parkinson's disease, and its metabolite, 
      desmethylselegiline, were explored for their neuroprotective effects against 
      N-methyl-D-aspartate (NMDA)-induced cell death in rat retina. Morphometric 
      analysis of the retina revealed that an intravitreal injection of NMDA induced a 
      significant decrease in cell density in the ganglion cell layer and in thickness 
      of the inner plexiform layer, but not of other retinal layers such as the outer 
      nuclear layer. Concurrent intravitreal injection of selegiline with NMDA did not 
      show a significant protective effect, whereas co-injection of desmethylselegiline 
      provided protection from NMDA-induced retinal damage. Parenteral administration 
      (both single and consecutive dosing) of selegiline significantly prevented loss 
      of ganglion cell layer cells. Counting of retinal ganglion cells by fluorescent 
      tracer labeling confirmed that selegiline protected retinal ganglion cells from 
      NMDA toxicity. The selegiline treatment did not produce a significant increase, 
      though it tended to such as effect, in a brain-derived neurotrophic factor (BDNF) 
      level in the retina, when compared with the NMDA-treated control group. These 
      results indicate that parenteral treatment with selegiline rescues inner retinal 
      cells from NMDA-induced neural damage, and that desmethylselegiline may 
      contribute, in part, to the protective activities of selegiline. The 
      neuroprotective effects exerted by selegiline may be attributed partially to a 
      change in the retinal BDNF expression.
FAU - Takahata, Kazue
AU  - Takahata K
AD  - Institute of Research and Development, Fujimoto Pharmaceutical Corporation, 
      1-3-40 Nishiotsuka, Osaka 580-8503, Matsubara, Japan.
FAU - Katsuki, Hiroshi
AU  - Katsuki H
FAU - Kobayashi, Yutaka
AU  - Kobayashi Y
FAU - Muraoka, Shizuko
AU  - Muraoka S
FAU - Yoneda, Fumio
AU  - Yoneda F
FAU - Kume, Toshiaki
AU  - Kume T
FAU - Kashii, Satoshi
AU  - Kashii S
FAU - Honda, Yoshihito
AU  - Honda Y
FAU - Akaike, Akinori
AU  - Akaike A
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Amphetamines)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - 2K1V7GP655 (Selegiline)
RN  - 5F44WR1I53 (desmethylselegiline)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
SB  - IM
MH  - Amphetamines/*pharmacology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Dizocilpine Maleate/pharmacology
MH  - Injections
MH  - Injections, Subcutaneous
MH  - Male
MH  - N-Methylaspartate/administration & dosage
MH  - Neurons/drug effects/pathology
MH  - Neuroprotective Agents/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retina/*drug effects/metabolism/pathology
MH  - Selegiline/*pharmacology
MH  - Superior Colliculi/drug effects/metabolism
MH  - Vitreous Body
EDAT- 2002/12/25 04:00
MHDA- 2003/05/17 05:00
CRDT- 2002/12/25 04:00
PHST- 2002/12/25 04:00 [pubmed]
PHST- 2003/05/17 05:00 [medline]
PHST- 2002/12/25 04:00 [entrez]
AID - S0014299902027292 [pii]
AID - 10.1016/s0014-2999(02)02729-2 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2003 Jan 1;458(1-2):81-9. doi: 10.1016/s0014-2999(02)02729-2.