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Modifications in Cytoskeletal and Astrocytic Proteins Content in Prefrontal Cortex, Hippocampus and Cerebellum of the Murine Model of Autism C58/J Strain

Poster Presentation
Thursday, May 10, 2018: 11:30 AM-1:30 PM
Hall Grote Zaal (de Doelen ICC Rotterdam)
I. Barón-Mendoza1 and A. González-Arenas2, (1)Instituto de Investigaciones Biomédicas, National Autonomous University of Mexico, Ciudad de México, Mexico, (2)National Autonomous University of Mexico, Ciudad de México, Mexico
Background:

Autism Spectrum Disorder (ASD) is presented with a global prevalence of 1/160. ASD have been recognized as a complex brain disorder with high heritability. Two common characteristics are presented in this disorder: impairment of social interaction and communication, and restricted and repetitive behaviours.

Alterations in neuritogenesis, elongation of axons and dendrites, and greater spine densities in ASD patients, particularly found in brain structures associated to memory, learning and motor processes as prefrontal cortex, hippocampus and cerebellum, besides a reported synaptic gene dysfunction, suggest connectional changes and disturbances in plasticity in the autistic brain. The cytoskeleton has a pivotal role in regulating the structure and dynamics of dendrites, spines and axon outgrowth. Also it is essential for synaptic connections stabilization and remodelling. Hence, some modifications of cytoskeletal and astrocyte components could be involved at molecular level in the mentioned alterations.

Objectives:

The objective of this research was to analyse changes in the content of cytoskeletal proteins β-actin and actin-binding-proteins cofilin and synaptopodin; α-tubulin and microtubules-associated proteins MAP2A and Tau, and astrocyte secreted protein thrombospondin-1 (TSP-1) in prefrontal cortex, hippocampus and cerebellum of an autistic animal model corresponding to the C58/J mice strain.

Methods: Prefrontal cortex, hippocampus and cerebellum from C58/J and C57 BL/6 (wild type) mice were dissected. Samples were processed for Western Blot technique.

Results: α-tubulin content showed no change in prefrontal cortex, neither hippocampus nor cerebellum between both strains. However microtubule-associated proteins as MAP2A and Tau presented clear differences. We observed six Tau isoforms with molecular weights between 20-100 kDa in prefrontal cortex, hippocampus and cerebellum of wild type mice strain (C57BL/6). Four Tau isoforms completely disappear in autistic brain areas, 80 and 60 kDa isoforms were detected in both strains. The 80 kDa Tau isoform content in prefrontal cortex, hippocampus and cerebellum of autistic mice (C58/J) was not different compared to the WT strain (C57 BL/6), but the 60 kDa isoform and its phosphorylated form showed a decrease in the autistic prefrontal cortex and hippocampus compared to the WT regions. Furthermore the MAP2A protein content was lower only in prefrontal cortex of autistic mice compared to WT strain. The content of β-actin was uniform in the studied brain areas between WT and autistic mice. Instead, the content of phosphorylated actin-binding protein cofilin showed a decrease in the autistic prefrontal cortex and an increase in autistic cerebellum. Besides, synaptopodin content, another actin-binding protein enriched in dendritic spines neck, was diminished only in hippocampus of autistic mice. Finally, the protein content of astrocyte-secreted protein thrombospondin-1 showed a decrease in prefrontal cortex and hippocampus of autistic mice, although the GFAP protein content was not different between both strains.

Conclusions:

Our work showed important brain structure-dependent changes in protein content of 60 kDa Tau/phospho-Tau isoform, MAP2A, phosphorylated-cofilin and synaptopodin, as well as differences in the astrocyte-secreted protein thrombospondin-1 content in prefrontal cortex, hippocampus and cerebellum of autistic animals (C58/J) compared to wild type mice (C57 BL/6). These differences in autistic mice brain could be associated with disturbances in neuronal cytoskeleton dynamics.

See more of: Animal Models
See more of: Animal Models