Author(s):
Silva, Ana P. 
; Pinheiro, Paulo S. ; Carvalho, Arsélio P. ; Carvalho, Caetana M. ; Jakobsen, Birthe ; Zimmer, Jens ; Malva, João O.
Date: 2003
Persistent ID: http://hdl.handle.net/10316/12831
Origin: Estudo Geral - Universidade de Coimbra
Subject(s): NPY; AMPA; Kainate; Neuroprotection; Neurodegeneration
Description
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 [Leu31,Pro34]NPY, 300 nM NPY13–36 or 1 μM 500 nM NPY(19–23)-
1 3 4 6 31 32 34
(Gly ,Ser ,Gln ,Thr ,Ala ,Aib ,Gln )-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
