BDNF-induced LTP in dentate gyrus is impaired with age: analysis of changes in cell signaling events.
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.
Department of Physiology, Trinity College Institute of Neuroscience, Trinity College, Dublin, Ireland.
Martina
M
Gooney
Elhoucine
E
Messaoudi
Frank O
FO
Maher
Clive R
CR
Bramham
Marina A
MA
Lynch
D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D018698:Glutamic Acid; D048049:Extracellular Signal-Regulated MAP Kinases