Otizm Spektrum Bozukluğunda Nöroinflamasyonun Sinaptik Plastiklik Üzerine Etkileri

Abstract

Ünal D. The Effects Of Neuroinflamation On Synaptic Plasticity In Autism Spectrum Disorders, Hacettepe University Graduate School of Health Sciences Basic Neurological Sciences (Neuroscience) Program, Doctor of Philosophy Thesis, Ankara, 2024. Neuroinflamation has been found to be related with Autism Spectrum Disorder (ASD) However, it is not clear how neuroinflamation causes autism symptoms as a mechanism. In our study, it is aimed to undertand the role of neuroinflamation in the pathophysiology of ASD by using a Poly (I:C) Maternal Immun Activiation (MIA) Model. We hyphothesized that M2 microglia phenotype would be seen more than M1 phenotype, due to the less synaptic pruning and, ASD related behaviours would be seen as a result of the increase in synaptic density. Behavioral tests assessing social behaviour, repetetive behaviour and learning were held in the first postnatal month. The generation of the Poly (I:C) injected mothers showed the socialization deficits dispersed as a spectrum as seen in the clinic. Thus, three separate groups were formed: the control (PBS) group, the stereotypic behavior movement-dominant Poly (I:C) group, and the social deficitdominant Poly (I:C) group. Afterwards animals were sacrificed and sagittal brain sections were analyzed. Regional thickness was measured for assessing synaptic pruning process in the medial prefrontal cortex, hippocampus, and striatum, which are known to be associated with ASD. Hippocampus was the only thicker region in stereotypic behaviour-dominant Poly (I:C) group. Also hippocampus thickness positively correlated with stereotypic behaviour. Striatum thickness was positively correlated with learning scores. The groups did not differ in terms of microglial number determined by Iba-1, Ym-1, CD86 labeling. Dendiritic spine number counting process could not be completed due to technical problems. Keywords: Autism Spectrum Disorder, neuroinflammation, maternal immun activation, synaptic pruning This study was supported by Hacettepe University Coordinatorship of Scientific Research Projects (18547).