Cerebellar and Striatal Implications in Autism Spectrum Disorders: From Clinical Observations to Animal Models
Abstract
:1. Introduction
2. Cerebellar Involvement in ASD
2.1. Structure and Function of the Cerebellum
2.2. Anatomical Evidence of Cerebellar Involvement in ASD
2.3. Cellular Correlates
2.4. Neurotransmission Systems Implicated
2.5. Evidence from Our Previous Work
3. Striatal Involvement in ASD
3.1. Anatomical Evidence of Striatal Involvement in ASD
3.2. Cellular Consequences Correlates
3.3. Neurotransmission Systems Implicated
4. Epigenetic Alterations in the Brain of ASD Animal Models
5. Conclusions and Future Direction
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Species | Treated Animal | Periodicity | Dose | Age of Treatment | Phenotype |
---|---|---|---|---|---|
Xenopus [13] | Embryo | 24 h exposition of the eggs |
| Stage 8 embryo |
|
C57BL/6J mice [25] | Pregnant female | One IP injection | 450 mg/kg | E12.5 |
|
C57BL/6J mice [16] | Pregnant female | One IP injection | 600 mg/kg | E12 |
|
C57BL/6J mice [26] | Pregnant female | One oral administration | 600 mg/kg | E12 |
|
CD-1 and GFAP-eGFP mice [27] | Pregnant female | One IP injection | 500 mg/kg | E12.5 |
|
FVB/NJ mice [28] | Pregnant female | One IP injection | 400 mg/kg | E11.5 or E12.75 | E11.5
E12.75
|
Long Evans rats [29] | Pregnant female | One IP injection | 600 mg/kg | E12.5 |
|
Long Evans rats [30] | Pregnant female | One oral administration | 800 mg/kg | E12 |
|
Sprague-Dawley rats [31] | Pregnant female | Two oral administrations | 800 mg/kg | E10 and E12 |
|
Winstar rats [32] | Young rat | Daily intragastric administration | 200 mg/kg | 1 month 3 months 6 months 9 months 12 months |
|
Winstar rats [33] | Pregnant female | One IP injection | 500 mg/kg | E12.5 |
|
Children | Teenagers | Adults | Animal Models | |||
---|---|---|---|---|---|---|
<5 years old | 5 to 14 years old | 14 to 21 years old | >21 years old | |||
Anatomical impairment | Global cerebellar volume |
|
|
|
= Shank3∆C/∆C, VPA and Poly I:C models [25,66,67] | |
White matter (WM) changes |
|
|
|
| ||
Connectivity |
|
|
| |||
Global right overconnectivity [73] | ||||||
Cellular correlates | Purkinje cell (PC) |
|
|
| PC arborization in LPS rats [84] Dendritic spine density in VPA rats [30] | |
Bergmann cells |
|
|
| |||
Microglia |
|
|
| |||
Neurotransmission | Glutamate |
|
| |||
GABA |
|
|
|
|
GABA-A β1 & β2 levels in Fmr1 KO [99] |
Children | Teenagers | Adults | Animal Models | |||
---|---|---|---|---|---|---|
<5 yo | 5 to 14 yo | 14 to 21 yo | >21 yo | |||
Anatomical impairment | Volume |
|
| |||
| ||||||
Matrice/striosome organization |
|
|
|
| ||
Cellular correlates | Medium spiny neurons |
|
|
| ||
PV interneurons |
|
| ||||
Astrocyte |
|
|
| |||
Microglia |
|
|
| |||
Neurotransmission | Glutamate |
|
|
|
| |
GABA |
|
|
|
|
sIPSCs & mIPSCs frequency in Fmr1 KO mice [175] | |
Dopamine |
|
|
|
|
|
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Thabault, M.; Turpin, V.; Maisterrena, A.; Jaber, M.; Egloff, M.; Galvan, L. Cerebellar and Striatal Implications in Autism Spectrum Disorders: From Clinical Observations to Animal Models. Int. J. Mol. Sci. 2022, 23, 2294. https://doi.org/10.3390/ijms23042294
Thabault M, Turpin V, Maisterrena A, Jaber M, Egloff M, Galvan L. Cerebellar and Striatal Implications in Autism Spectrum Disorders: From Clinical Observations to Animal Models. International Journal of Molecular Sciences. 2022; 23(4):2294. https://doi.org/10.3390/ijms23042294
Chicago/Turabian StyleThabault, Mathieu, Valentine Turpin, Alexandre Maisterrena, Mohamed Jaber, Matthieu Egloff, and Laurie Galvan. 2022. "Cerebellar and Striatal Implications in Autism Spectrum Disorders: From Clinical Observations to Animal Models" International Journal of Molecular Sciences 23, no. 4: 2294. https://doi.org/10.3390/ijms23042294