Specific regions display altered grey matter volume in μ-opioid receptor knockout mice: MRI voxel-based morphometry

被引：13

作者：

Sasaki, Kazumasu ^{[1
,2
]}

Sumiyoshi, Akira ^{[2
]}

Nonaka, Hiroi ^{[2
]}

Kasahara, Yoshiyuki ^{[1
]}

Ikeda, Kazutaka ^{[5
]}

Hall, F. Scott ^{[6
]}

Uhl, George R. ^{[6
]}

Watanabe, Masahiko ^{[7
]}

Kawashima, Ryuta ^{[2
,3
,4
]}

Sora, Ichiro ^{[1
,8
]}

机构：

[1] Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, Sendai, Miyagi 980, Japan

[2] Tohoku Univ, Dept Funct Brain Imaging, Sendai, Miyagi 980, Japan

[3] Tohoku Univ, Div Dev Cognit Neurosci, Sendai, Miyagi 980, Japan

[4] Tohoku Univ, Inst Dev Aging & Canc, Smart Ageing Int Res Ctr, Sendai, Miyagi 980, Japan

[5] Tokyo Metropolitan Inst Med Sci, Addict Subst Project, Tokyo 113, Japan

[6] NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD USA

[7] Hokkaido Univ, Grad Sch Med, Dept Anat, Sapporo, Hokkaido, Japan

[8] Kobe Univ, Dept Psychiat, Grad Sch Med, Kobe, Hyogo 6500017, Japan

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 2015年 / 172卷 / 02期

关键词：

GROWTH-FACTOR RECEPTOR; PERIAQUEDUCTAL GRAY; OLFACTORY-BULB; MOUSE-BRAIN; MORPHINE; NEUROGENESIS; ANALGESIA; ANTINOCICEPTION; PHARMACOLOGY; REGISTRATION;

D O I：

10.1111/bph.12807

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Background and Purpose Opioid receptor knockout (MOP-KO) mice display several behavioural differences from wild-type (WT) littermates including differential responses to nociceptive stimuli. Brain structural changes have been tied to behavioural alterations noted in transgenic mice with targeting of different genes. Hence, we assess the brain structure of MOP-KO mice. Experimental ApproachMagnetic resonance imaging (MRI) voxel-based morphometry (VBM) and histological methods were used to identify structural differences between extensively backcrossed MOP-KO mice and WT mice. Key ResultsMOP-KO mice displayed robust increases in regional grey matter volume in olfactory bulb, several hypothalamic nuclei, periaqueductal grey (PAG) and several cerebellar areas, most confirmed by VBM analysis. The largest increases in grey matter volume were detected in the glomerular layer of the olfactory bulb, arcuate nucleus of hypothalamus, ventrolateral PAG (VLPAG) and cerebellar regions including paramedian and cerebellar lobules. Histological analyses confirm several of these results, with increased VLPAG cell numbers and increased thickness of the olfactory bulb granule cell layer and cerebellar molecular and granular cell layers. Conclusions and ImplicationsMOP deletion causes previously undescribed structural changes in specific brain regions, but not in all regions with high MOP receptor densities (e.g. thalamus, nucleus accumbens) or that exhibit adult neurogenesis (e.g. hippocampus). Volume differences in hypothalamus and PAG may reflect behavioural changes including hyperalgesia. Although the precise relationship between volume change and MOP receptor deletion was not determined from this study alone, these findings suggest that levels of MOP receptor expression may influence a broader range of neural structure and function in humans than previously supposed. Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit

引用

页码：654 / 667

页数：14

共 65 条

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