Nicotine Rescues Depressive-like Behaviors via α7-type Nicotinic Acetylcholine Receptor Activation in CaMKIV Null Mice

Shigeki Moriguchi, Ryo Inagaki, Lusha Yi, Mikako Shibata, Hiroyuki Sakagami, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4929-4940
Number of pages12
JournalMolecular Neurobiology
Volume57
Issue number12
DOIs
Publication statusPublished - 2020 Dec 1

Keywords

  • Adult hippocampal neurogenesis
  • CaMKIV null mice
  • Depressive-like behaviors
  • Nicotine
  • α7-type nAChR

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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