Regulation of brain-derived neurotrophic factor mRNA levels in hippocampus by neuronal activity
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Regulation of brain-derived neurotrophic factor mRNA levels in hippocampus by neuronal activity. / Castrén, E; Berninger, B; Leingärtner, A; Lindholm, D.
in: PROG BRAIN RES, Jahrgang 117, 01.01.1998, S. 57-64.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Regulation of brain-derived neurotrophic factor mRNA levels in hippocampus by neuronal activity
AU - Castrén, E
AU - Berninger, B
AU - Leingärtner, A
AU - Lindholm, D
PY - 1998/1/1
Y1 - 1998/1/1
N2 - Neuronal activity increases synthesis of brain-derived neurotrophic factor (BDNF) mRNA in vivo and in vitro. We have investigated the pathways through which neuronal activity stimulated by kainic acid regulates BDNF mRNA levels in cultured hippocampal neurons and transgenic mice. Kainic acid induced the transcription of BDNF mRNA without influencing the mRNA stability. Interestingly, the half-life of the 4.2 kb BDNF transcript was much shorter than that of the 1.6 kb transcript (23 +/- 4 min. vs. 132 +/- 30 min). Increase in the BDNF mRNA levels by kainic acid was not blocked by the protein synthesis inhibitor cycloheximide demonstrating that BDNF is regulated as an immediate early gene in hippocampal neurons. Although calmodulin antagonists are known to abolish the effect of kainic acid on BDNF mRNA, this effect was very similar in Ca(+2)-calmodulin-dependent protein kinase II alpha knock-out mice and in wild-type mice. Surprisingly, even high doses of kainic acid failed to increase nerve growth factor (NGF) mRNA in mouse hippocampus although elevation in rat brain has been consistently observed.
AB - Neuronal activity increases synthesis of brain-derived neurotrophic factor (BDNF) mRNA in vivo and in vitro. We have investigated the pathways through which neuronal activity stimulated by kainic acid regulates BDNF mRNA levels in cultured hippocampal neurons and transgenic mice. Kainic acid induced the transcription of BDNF mRNA without influencing the mRNA stability. Interestingly, the half-life of the 4.2 kb BDNF transcript was much shorter than that of the 1.6 kb transcript (23 +/- 4 min. vs. 132 +/- 30 min). Increase in the BDNF mRNA levels by kainic acid was not blocked by the protein synthesis inhibitor cycloheximide demonstrating that BDNF is regulated as an immediate early gene in hippocampal neurons. Although calmodulin antagonists are known to abolish the effect of kainic acid on BDNF mRNA, this effect was very similar in Ca(+2)-calmodulin-dependent protein kinase II alpha knock-out mice and in wild-type mice. Surprisingly, even high doses of kainic acid failed to increase nerve growth factor (NGF) mRNA in mouse hippocampus although elevation in rat brain has been consistently observed.
KW - Animals
KW - Brain-Derived Neurotrophic Factor
KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2
KW - Calcium-Calmodulin-Dependent Protein Kinases
KW - Genes, Immediate-Early
KW - Hippocampus
KW - Kainic Acid
KW - Mice
KW - Mice, Knockout
KW - Nerve Growth Factors
KW - Neurons
KW - RNA, Messenger
KW - Rats
KW - Transcription, Genetic
M3 - SCORING: Journal article
C2 - 9932400
VL - 117
SP - 57
EP - 64
JO - PROG BRAIN RES
JF - PROG BRAIN RES
SN - 0079-6123
ER -