کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4338951 1614888 2011 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Gestational nicotine exposure regulates expression of AMPA and NMDA receptors and their signaling apparatus in developing and adult rat hippocampus
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Gestational nicotine exposure regulates expression of AMPA and NMDA receptors and their signaling apparatus in developing and adult rat hippocampus
چکیده انگلیسی

Untimely activation of nicotinic acetylcholine receptors (nAChRs) by nicotine results in short- and long-term consequences on learning and behavior. In this study, the aim was to determine how prenatal nicotine exposure affects components of glutamatergic signaling in the hippocampus during postnatal development. We investigated regulation of both nAChRs and glutamate receptors for AMPA and N-methyl-d-aspartate (NMDA), from postnatal day 1 (P1) to P63 after a temporally restricted exposure to saline or nicotine for 14 days in utero. We analyzed postsynaptic density components associated with AMPA receptor (AMPAR) and NMDA receptor (NMDAR) signaling: calmodulin (CaM), CaM Kinase II alpha (CaMKIIα), and postsynaptic density-95 (PSD95), as well as presynaptically localized synaptosomal-associated protein 25 (SNAP25). At P1, there was significantly heightened expression of AMPAR subunit GluR1 but not GluR2, and of NMDAR subunits NR1, NR2a, and NR2d but not NR2b. NR2c was not detectable. CaM, CaMKIIα, and PSD95 were also significantly upregulated at P1, together with presynaptic SNAP25. This enhanced expression of glutamate receptors and signaling proteins was concomitant with elevated levels of [3H]epibatidine ([3H]EB) binding in prenatal nicotine-exposed hippocampus, indicating that α4β2 nAChR may influence glutamatergic function in the hippocampus at P1. By P14, neither [3H]EB binding nor the expression levels of subunits GluR1, GluR2, NR1, NR2a, NR2b, NR2c, or NR2d seemed changed with prenatal nicotine. However, CaMKIIα was significantly upregulated with nicotine treatment while CaM showed downregulation at P14. The effects of nicotine persisted in P63 young adult brains which exhibited significantly downregulated GluR2, NR1, and NR2c expression levels in hippocampal homogenates and a considerably muted overall distribution of [3H]AMPA binding in areas CA1, CA2 and CA3, and the dentate gyrus. Our results suggest that prenatal nicotine exposure can regulate the glutamatergic signaling system throughout postnatal development by enhancing or inhibiting availability of AMPAR and NMDAR or their signaling components. The persistent depression, in adults, of the requisite NR1 subunit for NMDAR assembly, and of GluR2, important for assembly, trafficking, and biophysical properties of AMPAR, indicates that nicotine may alter ionotropic glutamate receptor stoichiometry and functional properties in adults after prenatally restricted nicotine exposure.

▶Gestational nicotine perturbs glutamatergic signaling apparatus in hippocampus. ▶AMPAR, NMDAR, and postsynaptic proteins are elevated in early postnatal development. ▶Elevated expression of glutamatergic apparatus coincides with enhanced α4β2 nAChR. ▶Prenatal nicotine represses GluR2, NR1, and NR2c expression in the adult. ▶AMPAR binding is repressed in adult hippocampus exposed to prenatal nicotine.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 188, 11 August 2011, Pages 168–181
نویسندگان
, , , ,