Glutamate, glutamine and GABA levels in the rat hippocampus in the pharmacological models of autism: a microdialysis study

• Autorzy: Diamandakis D. , Zieminska E. , Hilgier W. , Filipkowski R.K. , Polowy R. , Toczylowska B. , Lazarewicz J.W.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: The disorders of the glutamatergic neurotransmission have been implicated in the pathogenesis of autism, but data on brain content of glutamate (Glu) in patients and animal models are inconsistent. AIM(S): Aim of this study is to evaluate changes in the brain content of Glu, glutamine (Gln) and GABA in the rat models of pharmacologically-induced autism. METHOD(S): The rat females at the 11th day of gestation were given orally 800 mg/kg b.w. of valproic acid (VPA) or 500 mg/kg b.w. of thalidomide (THAL). The pups at PND 9 were submitted to ultrasonic vocalization (USV) test, and at PND 30, under anesthesia, to in vivo unilateral microdi alysis of the hippocampus with a calcium-containing medium. The samples of dialysate representing the basal level followed by a 40 min pulse of 100 mM KCl were collected. The contralateral hippocampi were prepared and homogenized. After derivatization of the amino acids with o-phtalaldehyde, the samples were submitted to HPLC analysis with a fluorescence detection. RESULTS: The results of USV tests showed that the pups prenatally treated with VPA, and to a greater extent with THAL, less frequently produced USV calls, which is regarded as impairment in social communication, a symptom characteristic of autism. In the male rats of the VPA and THAL groups, a total content of Glu increased to 143% and 158%, respectively, and also Gln and GABA contents were significantly elevated. All these values remained unchanged in the female rats. Basal levels of Glu, Gln and GABA in the dialysates of the hippocampi in the experimental groups did not differ from controls, however in VPA‑treated male rats during application of 100 mM KCl a reduction by 59% of Gln concentration and tendency to increase GABA level were found. CONCLUSIONS: The results demonstrate increased content of glutamate in the hippocampus of rats in two chemical models of autism, support a hypothesis on the role of the glutamatergic disturbances in the pathogenesis of autism. FINANCIAL SUPPORT: This study was supported by the Polish National Science Centre, grant no. 2014/15/B/ NZ4/04490.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.52-53

Twórcy

autor

Diamandakis D.

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

autor

Zieminska E.

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

autor

Hilgier W.

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

autor

Filipkowski R.K.

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

autor

Polowy R.

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

autor

Toczylowska B.

• Nalecz Institute of Biocybernetics and Biomedical Engineering Polish Academy of Sciences, Warsaw, Poland

autor

Lazarewicz J.W.

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