کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3055709 | 1186534 | 2011 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Functional changes in postsynaptic adenosine A2A receptors during early stages of a rat model of Huntington disease Functional changes in postsynaptic adenosine A2A receptors during early stages of a rat model of Huntington disease](/preview/png/3055709.png)
Huntington disease (HD) is a neurodegenerative disorder involving preferential loss of striatal GABAergic medium spiny neurons. Adenosine A2A receptors (A2ARs) are present in the striatum at both presynaptic and post-synaptic levels. Blocking pre-synaptic A2ARs, localized in glutamatergic terminals that contact striatal GABAergic dynorphinergic neurons, reduces glutamate release, which could be beneficial in HD. On the other hand, blockade of post-synaptic A2ARs, localized in striatal GABAergic enkephalinergic neurons, could exacerbate the motor dysfunction. To evaluate the function of pre- or post-synaptic A2ARs in HD we used selective antagonists for these receptors in a transgenic rat model of HD. Locomotor activity after systemic administration of the postsynaptic A2AR antagonist KW-6002 was used to investigate the function of post-synaptic A2ARs. The role of pre-synaptic A2ARs was instead evaluated by measuring the reduction of the electromyographic response of mastication muscles during electrical stimulation of the orofacial motor cortex after the systemic administration of the presynaptic A2AR antagonist SCH-442416. The ability of KW-6002 to produce locomotor activation was lost at 6 and 12 month-old of age in heterozygous and homozygous transgenic rats, but not in wild-type littermates. Nevertheless, no significant changes were observed up to 12 months of age in the potency of SCH-442416 to decrease the electromyographic response after cortical electrical stimulation. These results agree with a selective impairment of the striatal GABAergic enkephalinergic neuronal function during pre-symptomatic stages in HD. Since presynaptic A2AR function is not impaired, this receptor could probably be used as a target for the symptomatic treatment of the disease.
► Striatal adenosine A2A receptors are both presynaptic and post-synaptic.
► We studied their functional activity in a transgenic rat model of Huntington disease.
► Postsynaptic A2A receptor function was impaired between 3 and 6 months of age.
► Presynaptic A2A receptor function was not impaired up to 12 months of age.
► Results suggest an impairment of A2A receptor function during pre-symptomatic stages.
Journal: Experimental Neurology - Volume 232, Issue 1, November 2011, Pages 76–80