Jd. Mikkelsen et al., Intrahippocampal infusion of antisense oligodeoxynucleotide to the GABA(A)receptor gamma 2 subunit enhances neuropeptide Y gene expression, BRAIN RES B, 54(1), 2001, pp. 91-99
The effects of hippocampal treatment with a phosphorothioate oligodeoxynucl
eotide (ODN) antisense to the gamma -aminobutyric acid (GABA)(A) receptor g
amma2 subunit on neuropeptide Y (NPY) were studied. Adult male Wistar rats
were treated with unilateral intrahippocampal infusion of gamma2 subunit an
tisense ODN for 5 days. Rats infused with mismatch ODN and naive rats serve
d as controls. Brain sections were analysed for levels of NPY mRNA by in si
tu hybridisation, NPY-immunoreactivity (NPY-ir) by means of immunocytochemi
stry, and specific NPY binding sites by in vitro receptor autoradiography.
Following infusion of antisense ODN, a marked increase in cytoplasmic NPY-i
r was observed in hilar neurones of the fascia dentata, Further, intense NP
Y-ir was visualised in the mossy fibres and in cell bodies of the entorhina
l cortex and throughout the neocortex. High levels of NPY mRNA were detecte
d in the same cortical areas of antisense treated rats. A very large increa
se was observed in the piriform and parietal areas. NPY gene expression als
o occurred in the granular cell layer, in which no NPY mRNA could be detect
ed in normal animals. The level and distribution of cells displaying high l
evels of NPY mRNA differed among animals, perhaps as a result of the distin
ct anatomical location of ODN infusion. Finally, hippocampal levels of NPY
specific binding increased, suggesting that NPY neurotransmission is marked
ly increased. These findings are reminiscent of reported changes in the exp
ression of NPY mRNA and immunoreactivity in conditions of increased neurona
l excitation and support the usefulness of the present animal model for the
study of epileptic phenomena. (C) 2001 Elsevier Science Inc.