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Identifier

000463358

Title

Μελέτη προτύπων συμπεριφοράς σε ελλειματικούς για το συσχετιζόμενο με αυτισμό γονίδιο SATB1 μύες

Alternative Title

Behavioral phenotyping in a conditional KO mouse model for the autism associated gene SATB1

Author

Μαντούκα, Αδαμαντία-Ηλιάννα

Thesis advisor

Δεναξά, Μυρτώ

Reviewer

Σιδηροπούλου, Κυριακή
Σκαλιώρα, Ειρήνη

Abstract

GABAergic interneurons comprise 15-25% of all neurons in the cortex. They have multiple roles, from maintaining excitation/inhibition balance and synchronizing brain activity, to refining cortical circuits in the brain. Their functional diversity is enabled through their remarkable heterogeneity at the molecular, morphological and electrophysiological level. This diversity, although begins from early embryonic stages and depends on the unique combinatorial expression of transcription factors that characterize the place of origin of each interneuron type, it is better manifested at postnatal stages, when interneurons acquire their mature properties via inducing additional genetic programs, as a response to emerging environmental cues, such as network activity. As a consequence, deficits of the GABAergic system have been implicated in the etiology of several neurodevelopmental disorders such as Autism Spectrum Disorders (ASDs). We have previously shown that Satb1 is an activity-regulated transcription factor that is expressed at late embryonic stages, in the lineages of MGE-derived, parvalbumin (PV) and somatostatin (SST)-expressing interneurons, and it is implicated in their survival and differentiation in a cell-autonomous manner (Denaxa et al., 2012). In addition, in the absence of Satb1 function, MGE-derived cortical interneurons seem to have an aberrant transcriptional profile, with genes implicated in synapse organization, ion channel transmission, and neuropeptide regulation being down-regulated. These data are further supported, by defects in the morphology, as well as synapse number, of Satb1 mutant interneurons, both in vivo and in vitro. In this study, we investigate whether this disrupted inhibitory network in Satb1-cKO mice results in the manifestation of autism-like behaviors. We conducted a battery of behavioral experiments and we show that Satb1-cKO mice display impaired sociability, anxiety-like behaviors and hyperactivity which are identified by open-field and three-chamber social preference tests, along with increased self-grooming, a core symptom of repetitive behaviors. The findings suggest that SATB1 orchestrates a late-onset developmental molecular program in cortical interneurons, contributing to the onset of autistic-like behaviors when disturbed.

Language

English

Subject

Autism spectrum disorders

Behavioral experiments

MGE προερχόμενοι ενδονευρώνες

MGE-derived cortical interneurons

Διαταραχές του φάσματος του αυτισμού

Συμπεριφορικά πειράματα

Issue date

2024-04-17

Collection