PMID- 11406193
OWN - NLM
STAT- MEDLINE
DCOM- 20010906
LR  - 20220321
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 40
IP  - 8
DP  - 2001 Jun
TI  - Regulation of BDNF expression in primary neuron culture by LY392098, a novel AMPA 
      receptor potentiator.
PG  - 1019-27
AB  - The effects of a novel AMPA receptor potentiator (LY392098) on the expression of 
      brain-derived neurotrophic factor (BDNF) were examined in primary neuron culture. 
      The addition of either AMPA or LY392098 to cortical neurons elicited a time and 
      concentration dependent increase in mRNA encoding BDNF. Moreover, co-addition of 
      subeffective concentrations of AMPA (1 microM) and LY392098 (1 microM) resulted 
      in dramatic increases in both BDNF mRNA (>25-fold) and protein ( approximately 
      7-fold) levels, whilst no changes in either NT-3 or NT-4 mRNA were detected. More 
      modest ( approximately 1.5-2.5-fold) elevations in BDNF mRNA and protein 
      expression were also produced by combinations of AMPA and LY392098 in cerebellar 
      granule cell neurons. In contrast, AMPA and LY392098, either alone or in 
      combination, did not elevate BDNF mRNA levels in primary astroglial cultures. 
      Maximum elevations in BDNF mRNA and protein were produced by 6-12h of AMPA 
      receptor activation 1-3h of AMPA receptor activation were required to elevate 
      BDNF mRNA levels. AMPA receptor-mediated increases in BDNF mRNA and protein were 
      abolished by the AMPA antagonist, NBQX, but were unaffected by the NMDA 
      antagonist, MK-801. In cortical neuron cultures, activation of both L-type Ca(+2) 
      channels and mitogen-activated protein (MAP) kinases contribute to AMPA 
      receptor-mediated increases in BDNF mRNA. The ability of LY392098 to increase the 
      expression of BDNF in primary neuron culture indicates this and related 
      biarylpropylsulfonamides may be useful in the treatment of neuropsychiatric 
      disorders.
FAU - Legutko, B
AU  - Legutko B
AD  - Eli Lilly and Co., Lilly Research Laboratories, Corporate Center, Indianapolis, 
      IN 46285, USA. nflegutk@cyf-kr.edu.pl
FAU - Li, X
AU  - Li X
FAU - Skolnick, P
AU  - Skolnick P
LA  - eng
PT  - Journal Article
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Ciliary Neurotrophic Factor)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (LY 392098)
RN  - 0 (Neurotrophin 3)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Sulfonamides)
RN  - 0 (Thiophenes)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics/metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/drug effects/metabolism
MH  - Ciliary Neurotrophic Factor/drug effects/metabolism
MH  - Embryo, Mammalian
MH  - Excitatory Amino Acid Agonists/*pharmacology
MH  - Neurons/*drug effects/metabolism
MH  - Neurotrophin 3/drug effects/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, AMPA/*drug effects/metabolism
MH  - Sulfonamides/*pharmacology
MH  - Thiophenes/*pharmacology
EDAT- 2001/06/19 10:00
MHDA- 2001/09/08 10:01
CRDT- 2001/06/19 10:00
PHST- 2001/06/19 10:00 [pubmed]
PHST- 2001/09/08 10:01 [medline]
PHST- 2001/06/19 10:00 [entrez]
AID - S0028390801000065 [pii]
AID - 10.1016/s0028-3908(01)00006-5 [doi]
PST - ppublish
SO  - Neuropharmacology. 2001 Jun;40(8):1019-27. doi: 10.1016/s0028-3908(01)00006-5.