Early and adult hippocampal TGF-beta1 overexpression have opposite effects on behaviors relevant to autism

AMAICHA M. DEPINO; LUCIANA LUCCHINA

Florencia

Congreso; 8th IBRO World Congress of Neuroscience; 2011

International Brain Research Organization

TGF-beta1 is an anti-inflammatory cytokine that is augmented in the brain of autistic patients and that can affect brain development. In this work, we studied the effects of overexpressing TGF-beta1 in the dentate gyrus of adult or young mice on autism-related behaviors. TGF-beta1 overexpression during postnatal development led to long-term augmentation of behaviors associated to autism (while other behaviors were unaltered). Our analysis suggests that these behavioral changes are due both to direct effects of TGF-beta1, as well as to indirect mechanisms such as the downregulation of the synaptic protein neuroligin 3 and the induction of a decrease in the number of Reelin-positive neurons. In contrast, chronic expression of TGF-beta1 during adulthood resulted in a transient decrease in autism-related behaviors. These results suggest that the neuroinflammation observed in autistic brains is the consequence of an early-life alteration in brain development. Moreover, we present a neuroinflammatory mouse model for autism, which will be useful for elucidating the mechanisms involved in postnatal programming of autism-related behaviors.