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Meta-analysis of Voxel-Based Neuroimaging Studies using Seed-based d Mapping with Permutation of Subject Images SDM-PSI
Published on: November 27, 2019
Specific regions display altered grey matter volume in μ-opioid receptor knockout mice: MRI voxel-based morphometry
Kazumasu Sasaki1, Akira Sumiyoshi, Hiroi Nonaka
1Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Background And Purpose:
μ 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 Approach:
Magnetic 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 Results:
MOP-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 Implications:
MOP 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 Articles:
This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.
Insights
MOP receptor knockout mice show significant brain structural changes, including increased grey matter volume in the olfactory bulb, hypothalamus, and periaqueductal grey. These findings suggest MOP receptor expression influences broader neural structure and function.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- μ Opioid receptor knockout (MOP-KO) mice exhibit distinct behavioral responses compared to wild-type (WT) littermates.
- Previous studies link brain structural alterations to genetic modifications in mice.
- Investigating MOP-KO mice brain structure is crucial for understanding opioid receptor function.
Purpose of the Study:
- To assess and identify structural brain differences in MOP-KO mice.
- To correlate observed brain changes with MOP receptor deletion.
Main Methods:
- Magnetic resonance imaging (MRI) voxel-based morphometry (VBM) was employed.
- Histological analyses were performed to confirm MRI findings.
- Extensively backcrossed MOP-KO mice and WT littermates were used.
Main Results:
- MOP-KO mice showed increased grey matter volume in the olfactory bulb, hypothalamus, periaqueductal grey (PAG), and cerebellum.
- Specific regions like the ventrolateral PAG (VLPAG) and arcuate nucleus of the hypothalamus exhibited significant volume increases.
- Histology confirmed increased VLPAG cell numbers and thickened olfactory bulb and cerebellar layers.
Conclusions:
- MOP deletion induces novel structural brain changes in specific regions.
- These changes were not observed in all MOP receptor-rich areas or regions with adult neurogenesis.
- Hypothalamic and PAG volume differences may relate to behavioral changes like hyperalgesia, suggesting broader MOP receptor influence on neural function.
