Hiraoka Kotaro, Sumiyoshi Akira, Nonaka Hiroi, Kikkawa Takako, Kawashima Ryuta, Osumi Noriko
Division of Cyclotron Nuclear Medicine, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
Department of Functional Brain Imaging, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
PLoS One. 2016 Jun 29;11(6):e0158153. doi: 10.1371/journal.pone.0158153. eCollection 2016.
Pax6 is a transcription factor that pleiotropically regulates various developmental processes in the central nervous system. In a previous study, we revealed that Pax6 heterozygous mutant (rSey2/+) adult rats exhibit abnormalities in social interaction. However, the brain malformations underlying the behavioral abnormality are unknown. To elucidate the brain malformations in rSey2/+ rats, we morphometrically analyzed brains of rSey2/+ and wild type rats using small-animal magnetic resonance imaging (MRI). Sixty 10-week-old rats underwent brain MRI (29 rSey2/+ rats and 31 wild type rats). SPM8 software was used for image preprocessing and statistical image analysis. Normalized maps of the Jacobian determinant, a parameter for the expansion and/or contraction of brain regions, were obtained for each rat. rSey2/+ rats showed significant volume decreases in various brain regions including the neocortex, corpus callosum, olfactory structures, hippocampal formation, diencephalon, and midbrain compared to wild type rats. Among brain regions, the anterior commissure showed significant interaction between genotype and sex, indicating the effect of genotype difference on the anterior commissure volume was more robust in females than in males. The rSey2/+ rats exhibited decreased volume in various gray and white matter regions of the brain, which may contribute to manifestation of abnormal social behaviors.
Pax6是一种转录因子，可多效性地调节中枢神经系统中的各种发育过程。在先前的一项研究中，我们发现Pax6杂合突变体（rSey2/+）成年大鼠在社交互动方面表现出异常。然而，行为异常背后的脑畸形尚不清楚。为了阐明rSey2/+大鼠的脑畸形，我们使用小动物磁共振成像（MRI）对rSey2/+和野生型大鼠的大脑进行了形态计量分析。60只10周龄大鼠接受了脑部MRI检查（29只rSey2/+大鼠和31只野生型大鼠）。使用SPM8软件进行图像预处理和统计图像分析。为每只大鼠获得了雅可比行列式的归一化图，这是一个用于脑区扩张和/或收缩的参数。与野生型大鼠相比，rSey2/+大鼠在包括新皮层、胼胝体、嗅觉结构、海马结构、间脑和中脑在内的各个脑区的体积显著减小。在脑区中，前连合显示出基因型和性别的显著相互作用，表明基因型差异对前连合体积的影响在雌性中比在雄性中更强。rSey2/+大鼠在大脑的各种灰质和白质区域的体积减小，这可能导致异常社会行为的表现。
