PMID- 10627576
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20231014
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 20
IP  - 1
DP  - 2000 Jan 1
TI  - Positive modulation of AMPA receptors increases neurotrophin expression by 
      hippocampal and cortical neurons.
PG  - 8-21
AB  - This study investigated whether positive modulators of AMPA-type glutamate 
      receptors influence neurotrophin expression by forebrain neurons. Treatments with 
      the ampakine CX614 markedly and reversibly increased brain-derived neurotrophic 
      factor (BDNF) mRNA and protein levels in cultured rat entorhinal/hippocampal 
      slices. Acute effects of CX614 were dose dependent over the range in which the 
      drug increased synchronous neuronal discharges; threshold concentrations for 
      acute responses had large effects on mRNA content when applied for 3 d. 
      Comparable results were obtained with a second, structurally distinct ampakine 
      CX546. Ampakine-induced upregulation was broadly suppressed by AMPA, but not 
      NMDA, receptor antagonists and by reducing transmitter release. Antagonism of 
      L-type voltage-sensitive calcium channels blocked induction in entorhinal cortex 
      but not hippocampus. Prolonged infusions of suprathreshold ampakine 
      concentrations produced peak BDNF mRNA levels at 12 hr and a return to baseline 
      levels by 48 hr. In contrast, BDNF protein remained elevated throughout a 48 hr 
      incubation with the drug. Nerve growth factor mRNA levels also were increased by 
      ampakines but with a much more rapid return to control levels during chronic 
      administration. Finally, intraperitoneal injections of CX546 increased 
      hippocampal BDNF mRNA levels in aged rats and middle-aged mice. The present 
      results provide evidence of regional differences in mechanisms via which activity 
      regulates neurotrophin expression. Moreover, these data establish that changes in 
      synaptic potency produce sufficient network level physiological effects for 
      inducing neurotrophin genes, indicate that the response becomes refractory during 
      prolonged ampakine exposure, and raise the possibility of using positive AMPA 
      modulators to regulate neurotrophin levels in aged brain.
FAU - Lauterborn, J C
AU  - Lauterborn JC
AD  - Department of Anatomy and Neurobiology, University of California, Irvine, 
      California 92697-4292, USA. jclauter@uci.edu
FAU - Lynch, G
AU  - Lynch G
FAU - Vanderklish, P
AU  - Vanderklish P
FAU - Arai, A
AU  - Arai A
FAU - Gall, C M
AU  - Gall CM
LA  - eng
GR  - NS26748/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
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 (Excitatory Amino Acid Antagonists)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, AMPA)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Aging/physiology
MH  - Animals
MH  - Brain Chemistry/drug effects
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Cerebral Cortex/chemistry/*cytology/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Electrophysiology
MH  - Excitatory Amino Acid Antagonists/*pharmacology
MH  - Gene Expression/drug effects/physiology
MH  - Hippocampus/chemistry/*cytology/metabolism
MH  - Membrane Potentials/drug effects/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Growth Factor/genetics
MH  - Neurons/chemistry/*metabolism
MH  - Organ Culture Techniques
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Long-Evans
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/genetics
MH  - Receptors, AMPA/*genetics/metabolism
MH  - Up-Regulation/physiology
PMC - PMC6774091
EDAT- 2000/01/11 00:00
MHDA- 2000/01/11 00:01
PMCR- 2000/07/01
CRDT- 2000/01/11 00:00
PHST- 2000/01/11 00:00 [pubmed]
PHST- 2000/01/11 00:01 [medline]
PHST- 2000/01/11 00:00 [entrez]
PHST- 2000/07/01 00:00 [pmc-release]
AID - 3751 [pii]
AID - 10.1523/JNEUROSCI.20-01-00008.2000 [doi]
PST - ppublish
SO  - J Neurosci. 2000 Jan 1;20(1):8-21. doi: 10.1523/JNEUROSCI.20-01-00008.2000.