Maternal immune activation alters synaptic protein expression and causes social interaction impairment in rat offspring

• Autorzy: Cieslik M. , Gassowska-Dobrowolska M. , Jesko H. , Boguszewski P.M. , Filipkowski R.K. , Adamczyk A.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Emerging epidemiology data indicate that maternal immune activation (MIA) resulting from inflammatory stimuli such as bacterial infections during pregnancy may constitute a risk factor for multiple neurodevelopmental diseases including autism spectrum disorders (ASD). Genetic and environmental variation, inflammation during early development, and their interaction can influence synaptic dysfunction in ASD. However, the molecular links between infection-induced fetal development alterations and the risk of ASD are still unclear. AIM(S): The aim of this study was to investigate the effect of MIA on the expression and protein level of key synaptic proteins along with the autism-associated behavior in male rat offspring. METHOD(S): Pregnant Wistar rat dams were injected intraperitoneally (i.p.) at gestational day 9.5 with 0.1 mg/kg lipopolysaccharide (LPS), which induces immune response similar to that against gram-negative bacteria. RESULTS: Our data shown impaired social interaction, tested by the play behaviors (Tickling test on post-natal day PND 45–50). However, we did not observe any changes in ultrasonic vocalization (9–11 PND) and bedding preference (PND 15) in MIA offspring. Along with the social interaction changes, MIA has induced presynaptic protein alterations in adolescent rat offspring. These alterations included decreased level of synaptobrevin and syntaxin-1, the key components of SNARE complex, as well as higher level of synapsin. Together with changes in presynaptic proteins, MIA induced reduction in PSD-95 and down-regulation of SHANK family proteins. Moreover, alteration in the protein level of phospho-Akt, and 4E-BP1 was found in MIA subjects. CONCLUSIONS: It is possible that variations of Akt/ mTOR pathway are responsible for aberrant synthesis of key synaptic proteins. The altered synthesis of these proteins would generate changes in synaptic structure and function, contributing to ASD-like behaviors. FINANCIAL SUPPORT: Supported by the statutory theme 8.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.67-68

Twórcy

autor

Cieslik M.

• Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Gassowska-Dobrowolska M.

• Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Jesko H.

• Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Boguszewski P.M.

• Laboratory of Animal Models, Nencki Institute of Experimental Biology Polish Academy of Sciences, Warsaw, Poland

autor

Filipkowski R.K.

• Behavior and Metabolism Research Laboratory, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland

autor

Adamczyk A.

• Department of Cellular Signalling, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland