title: Activation of neuropeptide Y receptors is neuroprotective against excitotoxicity in organotypic hippocampal slice cultures.
abstract: 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 microM AMPA (alpha-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 microM [Leu31,Pro34]NPY, 300 nM NPY13-36 or 1 microM 500 nM NPY(19-23)-(Gly1,Ser3,Gln4,Thr6,Ala31,Aib32,Gln34)-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 microM 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.
authors.affiliation: Center for Neuroscience of Coimbra, Department of Zoology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Silva
authors.forename: Paulo S
authors.initials: PS
authors.lastname: Pinheiro
authors.forename: Arsélio P
authors.initials: AP
authors.lastname: Carvalho
authors.forename: Caetana M
authors.initials: CM
authors.lastname: Carvalho
authors.forename: Birthe
authors.initials: B
authors.lastname: Jakobsen
authors.forename: Jens
authors.initials: J
authors.lastname: Zimmer
authors.forename: João O
authors.initials: JO
authors.lastname: Malva
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007608:Kainic Acid / Q000633:toxicity; D009410:Nerve Degeneration / Q000139:chemically induced / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000378:metabolism; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018013:Receptors, Neuropeptide / Q000502:physiology; D017476:Receptors, Neuropeptide Y / Q000819:agonists* / Q000378:metabolism / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000633:toxicity
chemical_list: D018696:Neuroprotective Agents; D018013:Receptors, Neuropeptide; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; C106657:neuropeptide Y3 receptor; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid