TY - JOUR
T1 - Larger numbers of glial and neuronal cells in the periaqueductal gray matter of μ-opioid receptor knockout mice
AU - Sasaki, Kazumasu
AU - Hall, Frank Scott
AU - Uhl, George R.
AU - Sora, Ichiro
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Start-up 26893009).
Publisher Copyright:
© 2007 - 2018 Frontiers Media S.A. All Rights Reserved.
PY - 2018/9/19
Y1 - 2018/9/19
N2 - Background: μ-opioid receptor knockout (MOP-KO) mice display baseline hyperalgesia. We have recently identified changes in tissue volume in the periaqueductal gray matter (PAG) using magnetic resonance imaging voxel-based morphometry. Changes in the structure and connectivity of this region might account for some behavior phenotypes in MOP-KO mice, including hyperalgesia. Methods: Adult male MOP-KO and wild-type (WT) mice were studied. Immunohistochemistry was performed to detect microglia, astrocytes, and neurons in the PAG using specific markers: ionized calcium-binding adaptor molecule 1 (Iba-1) for microglia, glial fibrillary acidic protein (GFAP) for astrocytes, and the neuronal nuclei antigen (NeuN; product of the Rbfox3 gene) for neurons, respectively. Cell counting was performed in the four parallel longitudinal columns of the PAG (dorsomedial, dorsolateral, lateral, and ventrolateral) at three different locations from bregma (-3.5, -4.0, and -4.5 mm). Results: The quantitative analysis showed larger numbers of well-distributed Iba1-IR cells (microglia), NeuN-IR cells (neurons), and GFAP-IR areas (astrocytes) at all the anatomically distinct regions examined, namely, the dorsomedial (DM) PAG, dorsolateral (DL) PAG, lateral (L) PAG, and ventrolateral (VL) PAG, in MOP-KO mice than in control mice.Conclusions: The cellular changes in the PAG identified in this paper may underlie aspects of the behavioral alterations produced by MOP receptor deletion, and suggest that alterations in the cellular structure of the PAG may contribute to hyperalgesic states.
AB - Background: μ-opioid receptor knockout (MOP-KO) mice display baseline hyperalgesia. We have recently identified changes in tissue volume in the periaqueductal gray matter (PAG) using magnetic resonance imaging voxel-based morphometry. Changes in the structure and connectivity of this region might account for some behavior phenotypes in MOP-KO mice, including hyperalgesia. Methods: Adult male MOP-KO and wild-type (WT) mice were studied. Immunohistochemistry was performed to detect microglia, astrocytes, and neurons in the PAG using specific markers: ionized calcium-binding adaptor molecule 1 (Iba-1) for microglia, glial fibrillary acidic protein (GFAP) for astrocytes, and the neuronal nuclei antigen (NeuN; product of the Rbfox3 gene) for neurons, respectively. Cell counting was performed in the four parallel longitudinal columns of the PAG (dorsomedial, dorsolateral, lateral, and ventrolateral) at three different locations from bregma (-3.5, -4.0, and -4.5 mm). Results: The quantitative analysis showed larger numbers of well-distributed Iba1-IR cells (microglia), NeuN-IR cells (neurons), and GFAP-IR areas (astrocytes) at all the anatomically distinct regions examined, namely, the dorsomedial (DM) PAG, dorsolateral (DL) PAG, lateral (L) PAG, and ventrolateral (VL) PAG, in MOP-KO mice than in control mice.Conclusions: The cellular changes in the PAG identified in this paper may underlie aspects of the behavioral alterations produced by MOP receptor deletion, and suggest that alterations in the cellular structure of the PAG may contribute to hyperalgesic states.
KW - Astrocytes
KW - Immunohistochemistry
KW - Microglia
KW - Neuron
KW - Periaqueductal gray matter (PAG)
KW - μ opioid
KW - μ opioid receptor knockout (MOP-KO)
UR - http://www.scopus.com/inward/record.url?scp=85055089016&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055089016&partnerID=8YFLogxK
U2 - 10.3389/fpsyt.2018.00441
DO - 10.3389/fpsyt.2018.00441
M3 - Article
AN - SCOPUS:85055089016
VL - 9
JO - Frontiers in Psychiatry
JF - Frontiers in Psychiatry
SN - 1664-0640
IS - SEP
M1 - 441
ER -