TY - JOUR
T1 - Nicotine Rescues Depressive-like Behaviors via α7-type Nicotinic Acetylcholine Receptor Activation in CaMKIV Null Mice
AU - Moriguchi, Shigeki
AU - Inagaki, Ryo
AU - Yi, Lusha
AU - Shibata, Mikako
AU - Sakagami, Hiroyuki
AU - Fukunaga, Kohji
N1 - Funding Information:
This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology, and from the Ministry of Health and Welfare of Japan (KAKENHI 18 K06887 to S.M.) and in part by a grant from the Project of Translational and Clinical Research Core Centers from AMED of Japan (S.M.). This work was also supported by the Smoking Research Foundation (S.M.). We would like to thank Editage ( www.editage.com ) for English language editing.
Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - The nicotinic acetylcholine receptors (nAChRs) are essential for acetylcholine-mediated signaling. Two major functional subtypes of nAChR in the brain, α7-type and α4β2-type, have a high affinity for nicotine. Here, we demonstrated that chronic exposure to nicotine at 0.03–0.3 mg/kg for 14 days rescued depressive-like behavior in calcium/calmodulin-dependent protein kinase IV (CaMKIV) null mice. Chronic exposure to nicotine together with methyllycaconitine, an α7-type nAChR antagonist, but not with dihydro-β-erythroidine, an α4β2-type nAChR antagonist, failed to rescue the depressive-like behavior and restore the reduced number of BrdU-positive cells in the dentate gyrus (DG) of CaMKIV null mice. Furthermore, chronic exposure to nicotine enhanced the PI3K/Akt and ERK/CREB pathways and increased BDNF expression in the DG of CaMKIV null mice. Similar to chronic exposure to nicotine, both PNU-282987 and GTS-21, α7-type nAChR agonists, significantly rescued depressive-like behavior, with a reduction in the number of BrdU-positive cells in the DG of CaMKIV null mice. Both PNU-282987 and GTS-21 also enhanced the PI3K/Akt and ERK/CREB pathways and increased brain-derived neurotrophic factor (BDNF) expression in the DG of CaMKIV null mice. Taken together, we demonstrated that chronic exposure to nicotine rescues depressive-like behavior via α7-type nAChR through the activation of both PI3K/Akt and ERK/CREB pathways in CaMKIV null mice.
AB - The nicotinic acetylcholine receptors (nAChRs) are essential for acetylcholine-mediated signaling. Two major functional subtypes of nAChR in the brain, α7-type and α4β2-type, have a high affinity for nicotine. Here, we demonstrated that chronic exposure to nicotine at 0.03–0.3 mg/kg for 14 days rescued depressive-like behavior in calcium/calmodulin-dependent protein kinase IV (CaMKIV) null mice. Chronic exposure to nicotine together with methyllycaconitine, an α7-type nAChR antagonist, but not with dihydro-β-erythroidine, an α4β2-type nAChR antagonist, failed to rescue the depressive-like behavior and restore the reduced number of BrdU-positive cells in the dentate gyrus (DG) of CaMKIV null mice. Furthermore, chronic exposure to nicotine enhanced the PI3K/Akt and ERK/CREB pathways and increased BDNF expression in the DG of CaMKIV null mice. Similar to chronic exposure to nicotine, both PNU-282987 and GTS-21, α7-type nAChR agonists, significantly rescued depressive-like behavior, with a reduction in the number of BrdU-positive cells in the DG of CaMKIV null mice. Both PNU-282987 and GTS-21 also enhanced the PI3K/Akt and ERK/CREB pathways and increased brain-derived neurotrophic factor (BDNF) expression in the DG of CaMKIV null mice. Taken together, we demonstrated that chronic exposure to nicotine rescues depressive-like behavior via α7-type nAChR through the activation of both PI3K/Akt and ERK/CREB pathways in CaMKIV null mice.
KW - Adult hippocampal neurogenesis
KW - CaMKIV null mice
KW - Depressive-like behaviors
KW - Nicotine
KW - α7-type nAChR
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U2 - 10.1007/s12035-020-02077-z
DO - 10.1007/s12035-020-02077-z
M3 - Article
C2 - 32815115
AN - SCOPUS:85089597243
SN - 0893-7648
VL - 57
SP - 4929
EP - 4940
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 12
ER -