Premium
Homeostatic NMDA receptor down‐regulation via brain derived neurotrophic factor and nitric oxide‐dependent signalling in cortical but not in hippocampal neurons
Author(s) -
Sandoval Rodrigo,
González Andrés,
Caviedes Ariel,
Pancetti Floria,
Smalla KarlHeinz,
Kaehne Thilo,
Michea Luis,
Gundelfinger Eckart D.,
Wyneken Ursula
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07365.x
Subject(s) - neuroscience , nmda receptor , hippocampal formation , brain derived neurotrophic factor , nitric oxide , neurotrophic factors , glutamate receptor , neurotrophin , chemistry , homeostasis , receptor , biology , endocrinology , biochemistry
J. Neurochem. (2011) 118 , 760–772. Abstract Nitric oxide (NO) has been proposed to down‐regulate NMDA receptors (NMDA‐Rs) in a homeostatic manner. However, NMDA‐R‐dependent NO synthesis also can cause excitotoxic cell death. Using bicuculline‐stimulated hippocampal and cortical cell cultures, we have addressed the role of the brain‐derived neurotrophic factor‐NO pathway in NMDA‐R down‐regulation. This pathway protected cortical cells from NMDA‐induced death and led to NMDA‐R inhibition. In contrast, no evidence was gained for the presence of this protective pathway in hippocampal neurons, in which NMDA‐induced NO synthesis was confirmed to be toxic. Therefore, opposing effects of NO depended on the activation of different signalling pathways. The pathophysiological relevance of this observation was investigated in synaptosomes and post‐synaptic densities isolated from rat hippocampi and cerebral cortices following kainic acid‐induced status epilepticus . In cortical, but not in hippocampal synaptosomes, brain‐derived neurotrophic factor induced NO synthesis and inhibited NMDA‐R currents present in isolated post‐synaptic densities. In conclusion, we identified a NO‐dependent homeostatic response in the rat cerebral cortex induced by elevated activity. A low performance of this pathway in brain areas including the hippocampus may be related to their selective vulnerability in pathologies such as temporal lobe epilepsy.