Perinatal nicotine treatment induces transient increases in NACHO protein levels in the rat frontal cortex

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

SN - 0306-4522

VL - 346

SP - 278

EP - 283

JO - Neuroscience

JF - Neuroscience

ER -