Autism Spectrum Disorders (ASDs) are neurodevelopmental syndromes, characterized by behavioral deficits and a strong genetic background.
In the last decades, the synaptic pathway has been identified as one of the affected molecular signaling cascades in these disorders. Indeed, the communication among presynaptic and postsynaptic terminals is crucial for establishing proper synaptic function and animal behavior.
Neuroligin and dystrophin both act on the establishment of functional synapses. We propose to analyze glucocorticoids treatments in two mice models, one with a mutation in Neuroligin3 and the other with a deletion of dystrophin. Both animal models exhibit behavioral deficit having manifestations characteristic of ASDs. We propose to analyse the effects of glucocorticoids treatment on the molecular pathways involved in the glucocorticoid receptors signaling in the cerebellum and on the behaviour of mdx and R451C Neuroligin 3 mice, after subchronic DEX treatment, using tests known to be dependent on cerebellar integrity.
In the last years, the research field regarding ASD disorders has expanded from studying gene mutations to identifying alterations in molecular pathways. We propose to study the synaptic pathway in two animal models which have behavioural alterations, one is a model for a monogenic form of ASD, the other is the Duchenne muscular dystrophy mouse model presenting cognitive deficits. Specifically, our project proposes to analyse the effects of glucocorticoids in both animal models for rescuing impaired behaviours.
The identification of drugs to treat multifactorial diseases represent a challenge and the results of this approach could be expanded to other disorders having same behavioural manifestations.
Moreover, the heterogeneity of ASDs and the influence of environmental factors makes it difficult to develop a cure for these disorders. Indeed, so far only therapies against the main symptoms are available. This project can be considered as part of a new field of research, which aims to find a possible treatment for correlated diseases. This field is new and exciting and it opens a high number of possibilities for all those pathologies untreatable so far.