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Activation of neuropeptide Y receptors is neuroprotective against excitotoxicity in organotypic hippocampal slice cultures
Author(s) -
Silva Ana P.,
Pinheiro Paulo S.,
Carvalho Arsélio P.,
Carvalho Caetana M.,
Jakobsen Birthe,
Zimmer Jens,
Malva João O.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0885fje
Subject(s) - neuroprotection , kainate receptor , kainic acid , ampa receptor , glutamate receptor , excitotoxicity , hippocampal formation , neuropeptide y receptor , quinolinic acid , receptor , chemistry , neuroscience , neurodegeneration , biology , medicine , biochemistry , neuropeptide , amino acid , tryptophan , disease
Glutamate and NPY have been implicated in hippocampal neuropathology in temporal lobe epilepsy. Thus, we investigated the involvement of NPY receptors in mediating neuroprotection against excitotoxic insults in organotypic cultures of rat hippocampal slices. Exposure of hippocampal slice cultures to 2 μM AMPA (α‐amino‐3‐hydroxy‐5‐methyl‐isoxazole‐4‐propionate) induced neuronal degeneration, monitored by propidium iodide uptake, of granule cells and CA1 pyramidal cells. For dentate granule cells, selective activation of Y1, Y2, or Y5 receptors with 1 μM [Leu 31 ,Pro 34 ]NPY, 300 nM NPY13–36 or 1 μM 500 nM NPY(19–23)‐(Gly 1 ,Ser 3 ,Gln 4 ,Thr 6 ,Ala 31 ,Aib 32 ,Gln 34 )‐PP, respectively, had a neuroprotective effect against AMPA, whereas only the activation of Y2 receptors was effective for CA1 pyramidal cells. When the slice cultures were exposed to 6 μM kainate, the CA3 pyramidal cells displayed significant degeneration, and in this case the activation of Y1, Y2, and Y5 receptors was neuroprotective. For the kainic acid‐induced degeneration of CA1 pyramidal cells, it was again found that only the Y2 receptor activation was effective. Based on the present findings, it was concluded that Y1, Y2, and Y5 receptors effectively can modify glutamate receptor‐mediated neurodegeneration in the hippocampus.