Institutional creator:

Instytut Medycyny Doświadczalnej i Klinicznej im. M. Mossakowskiego PAN

Contributor:

Adamczyk, Agata (Promotor) ; Wilkaniec, Anna (Promotor pomocniczy)

Publisher:

Instytut Medycyny Doświadczalnej i Klicznej im. M. Mossakowskiego PAN

Place of publishing:

Warszawa

Description:

184 str.il., wykr., fot., tabl.; 30 cm. ; Bibliografia zawiera 185 pozycje.

Degree name:

doktor

Level of degree:

2

Degree discipline :

nauki medyczne

Type of object:

Praca dyplomowa

Abstract:

Autism Spectrum Disorders (ASD) are a group of heterogeneous neurodevelopmental disorders affecting approximately 1% of the global population. The etiology of ASD is complex, involving both environmental and genetic factors. Prenatal exposure to drugs, such as valproic acid, is one of the risk factors for ASD. Genetic background can be identified in 10-30% of autistic individuals. One of the most common monogenic disorders associated with ASD is the tuberous sclerosis complex (TSC), caused by mutations in the TSC1 or TSC2 genes, which inhibit the activity of the mTOR kinase. In 26-50% of TSC patients, behavioral symptoms characteristic of ASD are present. The mTOR pathway regulates translation, protein biosynthesis, and autophagy; its dysregulation can lead to abnormalities in the expression of synaptic proteins and receptors. Purinergic signaling plays a crucial role in regulating the structure and function of synapses. In the central nervous system (CNS), ATP and adenosine are released from neuronal and glial cells both in a regulated and uncontrolled manner. Synaptic ATP is degraded by ectonucleotidases, controlling the amount of bioavailable agonists that activate purinergic receptors (P1 for adenosine and P2 for nucleotides). Purinergic signaling mediates communication between CNS cells, regulating microglial activation and the release of pro-inflammatory cytokines. Additionally, ATP can enhance mTOR pathway signaling. There has been no comprehensive analysis of the interactions between purinergic signaling dysregulation, the mTOR pathway, and synaptic protein levels in ASD. Therefore, this doctoral dissertation aimed to investigate the involvement of purinergic signaling deregulation in mTOR-dependent alterations of key synaptic proteins and the development of ASD-like behaviors. The research was conducted using two ASD models: an environmental model, where ASD was induced by prenatal exposure to valproic acid (VPA), and a genetic model with Tsc2 gene knockdown mic

Detailed Resource Type:

PhD Dissertations

Resource Identifier:

oai:rcin.org.pl:242573

Source:

IMDiK PAN, sygn. ZS 438 ; click here to follow the link

Language:

pol

Language of abstract:

eng

Rights:

Creative Commons Attribution BY 4.0 license

Terms of use:

Copyright-protected material. [CC BY 4.0] May be used within the scope specified in Creative Commons Attribution BY 4.0 license, full text available at: ; -

Digitizing institution:

Mossakowski Medical Research Institute PAS

Original in:

Library of the Mossakowski Medical Research Institute PAS

Access:

Open