INTRODUCTION: An imbalance in excitatory/inhibitory neurotransmission has been implicated in the pathogenesis of autism. AIM(S): We tested this hypothesis by measuring with Magnetic Resonance Spectroscopy (MRS) and Nuclear Magnetic Resonance (NMR) the content of glutamate (Glu), glutamine (Gln) and GABA in the rat hippocampus in two pharmacological models of autism. METHOD(S): The rat females at the 11th day of gestation were given orally 800 mg/kg of valproic acid (VPA) or 500 mg/kg of thalidomide (THAL). The pups at PND 9 were submitted to ultrasonic vocalization (USV) test, and at PND 30, to MRS studies using the 7 T Bruker BioSpec 70/30 Avance III system. Spectrum was acquired with the short echo time PRESS sequence (TR/TE=2500/20 ms, 512 averages, 2048 points, scan time=17 min) with VAPOR water suppression, the outer volume suppression, frequency drift correction (flip angle 5°) and eddy current correction. Metabolite concentrations were estimated using the LCModel software. The amino acids from homogenates of rat hippocampi were extracted for NMR studies using the HCl-Bligh and Dyer procedure. Three-trimethylsilyl propionic acid (1 mM) was used as an internal reference signal. All NMR spectra were acquired at 25°C on a Avance III HD 500 MHz (Bruker) spectrometer. RESULTS: The results of USV tests showed that the “autistic pups” produced less calls/animal (VPA-122, THAL-33) as compared to control animals (295). MRS studies demonstrated increase by 21% and 20% in Glu content in the hippocampus of male rats from both, VPA- and THAL-treated groups, whereas Gln and GABA were on the control levels. NMR studies showed gender-dependent differences in Glu content in VPA-group (by 36%) and THAL‑group vs. control (by 16%); increased level of Gln in males from both groups (by 47% and 74%) and increased (by 86%) level of GABA in male VPA‑treated rats. CONCLUSIONS: These results are consistent with a hypothesis on the role of the imbalance in glutamatergic vs. GABAergic neurotransmission in the pathogenesis of autism. FINANCIAL SUPPORT: This study was supported by the Polish National Science Centre, grant no. 2014/15/B/ NZ4/04490.
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