Maternal immune activation dysregulates the synaptic ProSAP/Shank expression and might contribute to autism spectrum disorders

• Autorzy: Adamczyk A. , Cieslik M. , Jesko H. , Jaron K. , Dominiak A. , Smietanka U. , Boguszewski P.M.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Autism spectrum disorders (ASD) are neurodevelopmental diseases impairing social behaviour and cognition. Shank proteins that are involved in the maturation and maintenance of synaptic function have been implicated in the pathogenesis of ASD. Prenatal maternal immune activation (MIA) is a risk factor for ASD and is commonly used as animal model of ASD. METHODS: We investigated the effect of MIA on the expression of Shank1, 2, 3 in male offspring of Wistar rats ip injected with 0.1 mg/kg lipopolysaccharide at gestational day 9.5. Moreover, redox potential and pro-oxidative/pro-inflammatory proteins were analysed along with the autism-associated behaviour. Gene expression and protein levels were analysed using Real-time PCR and Western blot methods, respectively. Glutathione was measured spectrophotometrically. Behavioural tests were conducted to assess social communication, motions and anxiety, play behaviours as well as learning and memory. RESULTS: The data showed MIA-induced down-regulation of Shank1, 2 and 3 in the cerebral cortex, without changes in other brain structures. The GSH/GSSG ratio has been used as an indicator of oxidative stress. MIAslightly decreased the reduced GSH level butsignificantly elevated the GSSG level, which led to reduction of the GSH/GSSG ratio in brain cortex. Furthermore, we analysed the expression of cyclooxygenase-2 (COX-2) as well as 12-lipoxygenase (LOX-12) that may be engaged in oxidative stress depending on cellular redox state and found up-regulation of both COX-2 and LOX-12 in the cerebral cortex. Along with the biochemical changes MIAevoked a tendency towards impaired pup communication (ultrasonic vocalization) and learning and memory (Tmaze) in adult animals. CONCLUSIONS: Our findingsindicate MIA-induced down-regulation of Shank family and reduced antioxidative capacity. These changes may disturb synaptic function and social/cognitive behaviour. Supported from MMRC statutory theme 8.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S87-S88

Twórcy

autor

Adamczyk A.

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

autor

Cieslik 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

Jaron K.

• Department of Pharmaceutical Biology and Medicinal Plant Biotechnology, Medical University of Warsaw, Warsaw, Poland;

autor

Dominiak A.

• Department of Drug Bioanalysis and Analysis, Medical University of Warsaw, Warsaw, Poland; 4Laboratory of Limbic System, Department of Neurophysiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Smietanka U.

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

autor

Boguszewski P.M.

• Laboratory of Limbic System, Department of Neurophysiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland