Objectives: To investigate whether or not the BDNF/TrkB signaling pathway is disrupted in autism by comparing protein expression of TrkB isoforms and Akt in cortical tissue of autism versus control subjects.
Methods: We measured protein expression of TrkB isoforms by Western blotting in post-mortem fusiform gyrus tissue of autism (n=11) and control subjects (n=13), and determined TrkB-FL and truncated TrkB isoform ratios. As a downstream effector of the BDNF/TrkB pathway, we next examined total Akt protein expression by Western blotting in the same cohort.
Results: We found significantly increased truncated TrkB isoforms, significantly reduced TrkB-FL and a highly significant reduction of the TrkB-FL/truncated TrkB protein ratio in autism subjects compared to controls. Akt protein levels were also significantly decreased in autism compared to control tissue.
Conclusions: Decreased TrkB-FL and Akt levels in autism suggest downregulation of the BDNF/TrkB signaling pathway. In addition, increased truncated TrkB isoforms may abnormally sequester the high levels of BDNF seen in autism. These findings point to an impaired cellular response to BDNF in autism. Moreover, a dysfunctional PI3K-Akt-mTOR pathway activated by BDNF through TrkB receptors may contribute to changes in dendritic development, thereby affecting communication at synapses. Aberrant cellular response to BDNF may lead to defects in synaptic development and plasticity which could account for the behavioral deficits typical of autistic disorder.
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See more of: Biological Mechanisms