Perinatal nicotine treatment induces transient increases in NACHO protein levels in the rat frontal cortex
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Perinatal nicotine treatment induces transient increases in NACHO protein levels in the rat frontal cortex. / Wichern, Franziska; Jensen, Majbrit M; Christensen, Ditte Z; Mikkelsen, Jens D; Gondré-Lewis, Marjorie C; Thomsen, Morten S.
In: Neuroscience, Vol. 346, 27.03.2017, p. 278-283.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Perinatal nicotine treatment induces transient increases in NACHO protein levels in the rat frontal cortex
AU - Wichern, Franziska
AU - Jensen, Majbrit M
AU - Christensen, Ditte Z
AU - Mikkelsen, Jens D
AU - Gondré-Lewis, Marjorie C
AU - Thomsen, Morten S
N1 - Copyright © 2017 IBRO. All rights reserved.
PY - 2017/3/27
Y1 - 2017/3/27
N2 - The nicotinic acetylcholine receptor (nAChR) regulator chaperone (NACHO) was recently identified as an important regulator of nAChR maturation and surface expression. Here we show that NACHO levels decrease during early postnatal development in rats. This decrease occurs earlier and to a greater degree in the frontal cortex (FC) compared with the hippocampus (HIP). We further show that rats exposed to nicotine during pre- and postnatal development exhibit significantly higher NACHO levels in the FC at postnatal day (PND) 21, but not at PND60. Repeated exposure to nicotine selectively during early (PND8-14) or late (PND54-60) postnatal stages did not affect NACHO protein levels in the FC or HIP, neither did exposure to high doses of the selective α7 nAChR agonists SSR180711, A-582941, or PNU-282987. However, we found significantly increased NACHO protein levels in the FC of PND36 rats after a single exposure to a combination of nicotine and the type II α7 nAChR positive allosteric modulator (PAM) PNU-120596, but not the type I PAM AVL-3288. These findings suggest that exposure to nAChR agonism affects NACHO protein levels, and that this effect is more pronounced during pre- or early postnatal development. The effect of PNU-120596 further suggests that the increase in NACHO expression is caused by activation rather than desensitization of nAChRs.
AB - The nicotinic acetylcholine receptor (nAChR) regulator chaperone (NACHO) was recently identified as an important regulator of nAChR maturation and surface expression. Here we show that NACHO levels decrease during early postnatal development in rats. This decrease occurs earlier and to a greater degree in the frontal cortex (FC) compared with the hippocampus (HIP). We further show that rats exposed to nicotine during pre- and postnatal development exhibit significantly higher NACHO levels in the FC at postnatal day (PND) 21, but not at PND60. Repeated exposure to nicotine selectively during early (PND8-14) or late (PND54-60) postnatal stages did not affect NACHO protein levels in the FC or HIP, neither did exposure to high doses of the selective α7 nAChR agonists SSR180711, A-582941, or PNU-282987. However, we found significantly increased NACHO protein levels in the FC of PND36 rats after a single exposure to a combination of nicotine and the type II α7 nAChR positive allosteric modulator (PAM) PNU-120596, but not the type I PAM AVL-3288. These findings suggest that exposure to nAChR agonism affects NACHO protein levels, and that this effect is more pronounced during pre- or early postnatal development. The effect of PNU-120596 further suggests that the increase in NACHO expression is caused by activation rather than desensitization of nAChRs.
KW - Allosteric Regulation
KW - Animals
KW - Female
KW - Frontal Lobe
KW - Hippocampus
KW - Male
KW - Molecular Chaperones
KW - Nicotine
KW - Nicotinic Agonists
KW - Pregnancy
KW - Prenatal Exposure Delayed Effects
KW - Rats
KW - Rats, Sprague-Dawley
KW - Receptors, Nicotinic
KW - Journal Article
U2 - 10.1016/j.neuroscience.2017.01.026
DO - 10.1016/j.neuroscience.2017.01.026
M3 - Journal article
C2 - 28131622
VL - 346
SP - 278
EP - 283
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
ER -
ID: 187621674