Pituitary Adenylate Cyclase-Activating Polypeptide Modulates Dendritic Spine Maturation and Morphogenesis via MicroRNA-132 Upregulation

被引：17

作者：

Hayata-Takano, Atsuko ^{[1
,2
,3
,4
,5
,6
]}

Kamo, Toshihiko ^{[1
]}

Kijima, Harui ^{[1
]}

Seiriki, Kaoru ^{[1
,7
]}

Ogata, OKatsuya ^{[1
]}

Ago, Yukio ^{[1
,8
]}

Nakazawa, Takanobu ^{[1
,9
]}

Shintani, Yusuke ^{[1
]}

Higashino, Kosuke ^{[1
]}

Nagayasu, OKazuld ^{[1
]}

Shintani, Norihito ^{[1
]}

Kasai, Atsushi ^{[1
]}

Waschek, James A. ^{[10
]}

Hashimoto, Hitoshi ^{[1
,2
,3
,4
,5
,6
,11
,12
]}

机构：

[1] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Mol Neuropharmacol, Suita, Osaka 5650871, Japan

[2] Osaka Univ, United Grad Sch Child Dev, Suita, Osaka 5650871, Japan

[3] Kanazawa Univ, Suita, Osaka 5650871, Japan

[4] Hamamatsu Univ Sch Med, Suita, Osaka 5650871, Japan

[5] Chiba Univ, Suita, Osaka 5650871, Japan

[6] Univ Fukui, Suita, Osaka 5650871, Japan

[7] Osaka Univ, Inst Transdisciplinary Grad Degree Programs, Suita, Osaka 5650871, Japan

[8] Osaka Univ, Grad Sch Pharmaceut Sci, Lab Biopharmaceut, Suita, Osaka 5650871, Japan

[9] Osaka Univ, Grad Sch Dent, Dept Pharmacol, Suita, Osaka 5650871, Japan

[10] Univ Calif Los Angeles, David Geffen Sch Med, Intellectual Dev & Disabil Res Ctr, Los Angeles, CA 90095 USA

[11] Osaka Univ, Inst Databil Sci, Div Biosci, Suita, Osaka 5650871, Japan

[12] Osaka Univ, Inst Open & Transdisciplinary Res Initiat, Transdimens Life Imaging Div, Suita, Osaka 5650871, Japan

来源：

JOURNAL OF NEUROSCIENCE | 2019年 / 39卷 / 22期

基金：

日本学术振兴会;

关键词：

CA1; dendritic spine; miRNA; morphogenesis; PACAP; NEUROTROPHIC FACTOR EXPRESSION; PACAP-DEFICIENT MICE; CYCLIC-AMP; RECEPTOR; BRAIN; PROTEIN; SCHIZOPHRENIA; BDNF; DYSREGULATION; PLASTICITY;

D O I：

10.1523/JNEUROSCI.2468-18.2019

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Alterations in pituitary adenylate cyclase-activating polypeptide (PACAP), a multifunctional neuropeptide, and its receptors have been identified as risk factors for certain psychiatric disorders, including schizophrenia. Increasing evidence from human genetic and animal model studies suggest an association between various psychiatric disorders and altered dendritic spine morphology. In the present study, we investigated the role of exogenous and endogenous PACAP in spine formation and maturation. PACAP modified the density and morphology of PSD-95-positive spines in primary cultured hippocampal neurons. Notably, PACAP increased the levels of microRNA (miR)-132 and decreased expression of corresponding miR-132 target genes and protein expression of p250GAP, a miR-132 effector known to be involved in spine morphology regulation. In corroboration, PSD-95-positive spines were reduced in PACAP-deficient (PACAP(-/-)) mice versus WT mice. Golgi staining of hippocampal CA1 neurons revealed a reduced spine densities and atypical morphologies in the male PACAP(-/-) mice. Furthermore, viral miR-132 overexpression reversed the reduction in hippocampal spinal density in the male PACAP (-/-) mice. These results indicate that PACAP signaling plays a critical role in spine morphogenesis possibly via miR-132. We suggest that dysfunction of PACAP signaling may contribute to the pathogenesis of neuropsych iatric disorders, at least partly through its effects on spine formation.

引用

页码：4208 / 4220

页数：13

共 64 条

[1] The selective metabotropic glutamate 2/3 receptor agonist MGS0028 reverses psychomotor abnormalities and recognition memory deficits in mice lacking the pituitary adenylate cyclase-activating polypeptide [J].