TY - JOUR
T1 - BDNF-induced LTP in dentate gyrus is impaired with age
T2 - Analysis of changes in cell signaling events
AU - Gooney, Martina
AU - Messaoudi, Elhoucine
AU - Maher, Frank O.
AU - Bramham, Clive R.
AU - Lynch, Marina A.
N1 - Funding Information:
Funded by the European Union Biotechnology program (BIO4-CT98-0333) and the Norwegian Foundation for Public Health. BDNF for in vivo perfusion was provided by Amgen-Regeneron Partners.
PY - 2004/11
Y1 - 2004/11
N2 - Brain-derived neurotrophic factor (BDNF) has emerged as a major regulator of synaptic plasticity in the adult brain and acute BDNF infusion has been shown to trigger long-term potentiation (BDNF-LTP) in adult rats. Here we compared the effects of acute BDNF infusion in young adult and aged anesthetized rats. In young rats, BDNF-LTP was accompanied by increased activation of the BDNF receptor TrkB, and extracellular signal-regulated kinase (ERK), as well as enhanced evoked release of glutamate in synaptosomes prepared from DG. In aged rats, both BDNF-LTP and the associated signaling were significantly impaired, while analysis of untreated hippocampal tissue from aged rats showed that activation of TrkB and ERK were decreased. In addition to effects in the DG, BDNF-LTP was accompanied by robust phosphorylation of the calcium/cAMP- responsive element binding protein (CREB) in tissue prepared from entorhinal cortex of both young and aged rats. These results suggest a cascade of presynaptic changes contributing to the expression of BDNF-induced LTP and show that BDNF-induced transduction mechanisms are attenuated with age.
AB - Brain-derived neurotrophic factor (BDNF) has emerged as a major regulator of synaptic plasticity in the adult brain and acute BDNF infusion has been shown to trigger long-term potentiation (BDNF-LTP) in adult rats. Here we compared the effects of acute BDNF infusion in young adult and aged anesthetized rats. In young rats, BDNF-LTP was accompanied by increased activation of the BDNF receptor TrkB, and extracellular signal-regulated kinase (ERK), as well as enhanced evoked release of glutamate in synaptosomes prepared from DG. In aged rats, both BDNF-LTP and the associated signaling were significantly impaired, while analysis of untreated hippocampal tissue from aged rats showed that activation of TrkB and ERK were decreased. In addition to effects in the DG, BDNF-LTP was accompanied by robust phosphorylation of the calcium/cAMP- responsive element binding protein (CREB) in tissue prepared from entorhinal cortex of both young and aged rats. These results suggest a cascade of presynaptic changes contributing to the expression of BDNF-induced LTP and show that BDNF-induced transduction mechanisms are attenuated with age.
KW - Aging
KW - Brain-derived neurotrophic factor (BDNF)
KW - Dentate gyrus
KW - Extracellular signal-regulated kinase (ERK)
KW - Glutamate
KW - Hippocampus
KW - Long-term potentiation (LTP)
KW - Synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=4644351697&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2004.01.003
DO - 10.1016/j.neurobiolaging.2004.01.003
M3 - Article
C2 - 15465630
AN - SCOPUS:4644351697
SN - 0197-4580
VL - 25
SP - 1323
EP - 1331
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 10
ER -