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

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

doi:10.1007/s12035-020-02077-z

Cited by 12 publications

(13 citation statements)

References 67 publications

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“… 27 PNU-282987 upregulated p-ERK1/2, p-CREB, and BDNF expression and decreased the number of BrdU-positive cells in the DG region of the hippocampus in CaMKIV null mice. 28 In CIH-treated mice, Wang et al observed that neurocognitive dysfunction caused by CIH was associated with ERK1/2 phosphorylation and CREB expression. 13 The results of the present study showed increased p-ERK1/2 and p-CREB expression in the hippocampus of mice after injection of the α7nAChR-specific agonist PNU-282987 compared to that in the CIH group.…”

Section: Discussionmentioning

confidence: 99%

α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia

Shen¹,

Meng²,

Liú³

et al. 2021

NSS

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Purpose: Cognitive impairment is an important complication of obstructive sleep apnea (OSA). Chronic intermittent hypoxia (CIH), the main pathophysiological characteristics of OSA, is closely related to cognitive dysfunction and may be mediated by alpha-7 nicotinic acetylcholine receptors (α7nAChR). This study investigated the effects and clarified the mechanisms of α7nAChR on the cognitive function of mice with CIH. Methods: Thirty CD-1 mice were randomly divided into room air (RA), CIH-2 weeks (CIH2W), and CIH-4 weeks (CIH4W) groups. Cognitive function was evaluated by novel object recognition (NOR) and Morris water maze (MWM) tests after exposure. Then, 104 CD-1 mice were exposed to CIH for 4 weeks and randomly divided into four groups: CIH4W (control), with dimethyl sulfoxide (DMSO) (sham), with α7nAChR-specific agonist PNU-282987 (PNU), and with α7nAChR-specific inhibitor methyllycaconitine and PNU-282987 (MLA+PNU). In addition to the evaluation of cognitive function, apoptotic bodies in the hippocampus were detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, changes in p-CREB and BDNF were detected by immunohistochemistry, while those of ERK1/2, CREB, PGC-1α, FNDC5, and BDNF were detected by Western blotting in the hippocampal tissues of the mice. Results: Compared to the CIH2W and RA groups, the CIH4W group showed cognitive dysfunction in the NOR and MWM tests. The changes in cognitive dysfunction were alleviated by PNU-282987; furthermore, MLA pretreatment offset the effect. In hippocampal tissues, TUNEL assays showed decreased apoptotic cells, immunohistochemical staining showed increased expressions of p-CREB and BDNF. The expression levels of p-ERK1/2/ t-ERK1/2, p-CREB/t-CREB, PGC-1α, FNDC5, and BDNF were increased after PNU-282987 injection. Conclusion: Four weeks of CIH caused cognitive dysfunction in mice. Activating α7nAChR might ameliorate this dysfunction by upregulating the ERK1/2/CREB signaling pathway; enhancing PGC-1α, FNDC5, and BDNF expression levels; and reducing cell apoptosis in the hippocampal tissue of mice.

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Section: Discussionmentioning

confidence: 99%

α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia

Shen¹,

Meng²,

Liú³

et al. 2021

NSS

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“…Moreover, nicotine was shown to activate CAMKII in hippocampal neurons from mice with depressive-like behavior. The specific α7 nAChRs antagonist mecamylamine blocks this activation [ 60 ]. Furthermore, Ca 2+ increases at levels capable of activating Ca 2+ signaling systems have been observed upon activation of α7 nAChRs.…”

Section: Dendritic Spines the Postsynaptic Specialization Of Excitatory Synapses In The Brainmentioning

confidence: 99%

“…Nicotine activates the PI3K/Akt and ERK/CREB pathways that increase the expression of the neurotrophic factor, BDNF. In addition, potentiation of synaptic efficacy is also observed through CaMKII activation [ 60 ].…”

Section: Functional Pharmacology Of Brain Nachr-mediated Synaptic Plasticitymentioning

confidence: 99%

Homomeric and Heteromeric α7 Nicotinic Acetylcholine Receptors in Health and Some Central Nervous System Diseases

Borroni

Barrantes

2021

Membranes

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Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels involved in the modulation of essential brain functions such as memory, learning, and attention. Homomeric α7 nAChR, formed exclusively by five identical α7 subunits, is involved in rapid synaptic transmission, whereas the heteromeric oligomers composed of α7 in combination with β subunits display metabotropic properties and operate in slower time frames. At the cellular level, the activation of nAChRs allows the entry of Na+ and Ca2+; the two cations depolarize the membrane and trigger diverse cellular signals, depending on the type of nAChR pentamer and neurons involved, the location of the intervening cells, and the networks of which these neuronal cells form part. These features make the α7 nAChR a central player in neurotransmission, metabolically associated Ca2+-mediated signaling, and modulation of diverse fundamental processes operated by other neurotransmitters in the brain. Due to its ubiquitous distribution and the multiple functions it displays in the brain, the α7 nAChR is associated with a variety of neurological and neuropsychiatric disorders whose exact etiopathogenic mechanisms are still elusive.

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“…Brain regions prefrontal cortex [10,11], hippocampus [12,13], amygdala [14], lateral habenula [15,16] hippocampus [17], nucleus accumbens [18] Cell types isoforms α and β: brain neurons; isoforms γ and δ: present in every examined tissue [19,20] nervous tissue (mostly in cerebellum's granular cells [21]), thymus (especially T-lymphocytes), spleen, and testis [22] Function regulation of various cellular functions by phosphorylating a wide range of substrates, e.g., regulation of immune system [23][24][25], cardiac function [26][27][28], pain [29] regulation of various cellular functions by phosphorylating a wide range of substrates, e.g., controlling transcription factors such as CREB, ATF-1, SRF [30][31][32][33], blood pressure [34], immune system [35][36][37], microtubule dynamics [38] Examples of dysfunction and associated disease-like state in rodents abnormal phosphorylation-Angelman syndrome [39], β isoform overexpression-depressive-like symptoms [15], β isoform knockout-anxiety-related behavior [40], inhibition of α isoform expression-anxiolytic-like effect [41] overexpression and increased activity-various types of cancer [42], knockout or inhibition-depressive-like state [17,43]…”

Section: Camkii Camkivmentioning

confidence: 99%

“…A number of drugs, compounds, or therapies elicit their antidepressant-like activity probably via CaMKIV pathway’s modulation. In CaMKIV knockout mice, chronic nicotine treatment decreased depressive-like behavior via alfa7-nAChRs (nicotinic acetylcholine receptors) and subsequent activation of this signaling pathway [ 43 ]. The reversal of depressive-like phenotype in CaMKIV knockout mice also occurred after sigma-1 receptor stimulation.…”

Section: Depression-like State In Rodentsmentioning

confidence: 99%

The Calcium/Calmodulin-Dependent Kinases II and IV as Therapeutic Targets in Neurodegenerative and Neuropsychiatric Disorders

Sałaciak

Koszałka

Żmudzka

et al. 2021

IJMS

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CaMKII and CaMKIV are calcium/calmodulin-dependent kinases playing a rudimentary role in many regulatory processes in the organism. These kinases attract increasing interest due to their involvement primarily in memory and plasticity and various cellular functions. Although CaMKII and CaMKIV are mostly recognized as the important cogs in a memory machine, little is known about their effect on mood and role in neuropsychiatric diseases etiology. Here, we aimed to review the structure and functions of CaMKII and CaMKIV, as well as how these kinases modulate the animals’ behavior to promote antidepressant-like, anxiolytic-like, and procognitive effects. The review will help in the understanding of the roles of the above kinases in the selected neurodegenerative and neuropsychiatric disorders, and this knowledge can be used in future drug design.

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

Cited by 12 publications

References 67 publications

α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia

α7 Nicotinic Acetylcholine Receptor Agonist PNU-282987 Ameliorates Cognitive Impairment Induced by Chronic Intermittent Hypoxia

Homomeric and Heteromeric α7 Nicotinic Acetylcholine Receptors in Health and Some Central Nervous System Diseases

The Calcium/Calmodulin-Dependent Kinases II and IV as Therapeutic Targets in Neurodegenerative and Neuropsychiatric Disorders

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