TY - JOUR
T1 - Shank3 transgenic and prenatal zinc-deficient autism mouse models show convergent and individual alterations of brain structures in MRI
AU - Schoen, Michael
AU - Asoglu, Harun
AU - Bauer, Helen F.
AU - Müller, Hans Peter
AU - Abaei, Alireza
AU - Sauer, Ann Katrin
AU - Zhang, Rong
AU - Song, Tian Jia
AU - Bockmann, Juergen
AU - Kassubek, Jan
AU - Rasche, Volker
AU - Grabrucker, Andreas M.
AU - Boeckers, Tobias M.
N1 - Publisher Copyright:
© 2019 Schoen, Asoglu, Bauer, Müller, Abaei, Sauer, Zhang, Song, Bockmann, Kassubek, Rasche, Grabrucker and Boeckers.
PY - 2019/1/28
Y1 - 2019/1/28
N2 - Research efforts over the past decades have unraveled both genetic and environmental factors, which contribute to the development of autism spectrum disorders (ASD). It is, to date, largely unknown how different underlying causes result in a common phenotype. However, the individual course of development and the different comorbidities might reflect the heterogeneous genetic and non-genetic contributions. Therefore, it is reasonable to identify commonalities and differences in models of these disorders at the different hierarchical levels of brain function, including genetics/environment, cellular/synaptic functions, brain regions, connectivity, and behavior. To that end, we investigated Shank3 transgenic mouse lines and compared them with a prenatal zinc-deficient (PZD) mouse model of ASD at the level of brain structural alterations in an 11,7 T small animal magnetic resonance imaging (MRI). Animals were measured at 4 and 9 weeks of age. We identified a decreased total brain volume (TBV) and hippocampal size of Shank3−/− mice but a convergent increase of basal ganglia (striatum and globus pallidus) in most mouse lines. Moreover, Shank3 transgenic mice had smaller thalami, whereas PZD mice had this region enlarged. Intriguingly, Shank3 heterozygous knockout mice mostly showed minor abnormalities to full knockouts, which might reflect the importance of proper Shank3 dosage in neuronal cells. Most reported volume changes seemed to be more pronounced at younger age. Our results indicate both convergent and divergent brain region abnormalities in genetic and non-genetic models of ASD. These alterations of brain structures might be mirrored in the reported behavior of both models, which have not been assessed in this study.
AB - Research efforts over the past decades have unraveled both genetic and environmental factors, which contribute to the development of autism spectrum disorders (ASD). It is, to date, largely unknown how different underlying causes result in a common phenotype. However, the individual course of development and the different comorbidities might reflect the heterogeneous genetic and non-genetic contributions. Therefore, it is reasonable to identify commonalities and differences in models of these disorders at the different hierarchical levels of brain function, including genetics/environment, cellular/synaptic functions, brain regions, connectivity, and behavior. To that end, we investigated Shank3 transgenic mouse lines and compared them with a prenatal zinc-deficient (PZD) mouse model of ASD at the level of brain structural alterations in an 11,7 T small animal magnetic resonance imaging (MRI). Animals were measured at 4 and 9 weeks of age. We identified a decreased total brain volume (TBV) and hippocampal size of Shank3−/− mice but a convergent increase of basal ganglia (striatum and globus pallidus) in most mouse lines. Moreover, Shank3 transgenic mice had smaller thalami, whereas PZD mice had this region enlarged. Intriguingly, Shank3 heterozygous knockout mice mostly showed minor abnormalities to full knockouts, which might reflect the importance of proper Shank3 dosage in neuronal cells. Most reported volume changes seemed to be more pronounced at younger age. Our results indicate both convergent and divergent brain region abnormalities in genetic and non-genetic models of ASD. These alterations of brain structures might be mirrored in the reported behavior of both models, which have not been assessed in this study.
KW - Animal MRI
KW - ASD
KW - Autism mouse models
KW - Brain structures
KW - SHANK3
KW - Zinc deficiency
UR - http://www.scopus.com/inward/record.url?scp=85062695481&partnerID=8YFLogxK
U2 - 10.3389/fncir.2019.00006
DO - 10.3389/fncir.2019.00006
M3 - Article
C2 - 30853900
AN - SCOPUS:85062695481
SN - 1662-5110
VL - 13
SP - 6
JO - Frontiers in Neural Circuits
JF - Frontiers in Neural Circuits
M1 - 6
ER -