A gain-of-function study of amelioration of pentylenetetrazole-induced seizures by endogenous prostaglandin D2

Publication date: Available online 7 September 2018Source: Neuroscience LettersAuthor(s): Mahesh K. Kaushik, Kosuke Aritake, Yoan Cherasse, Rahul Sharma, Yoshihiro UradeAbstractWe previously showed that knockout mice of hematopoietic prostaglandin (PG) D synthase (H-PGDS) produce less PGD2 to exacerbate pentylenetetrazole (PTZ)-induced seizures. Here, we adopted a gain-of-function strategy and used transgenic mice that over-express human H-PGDS enzyme, to elucidate the role of overproduction of endogenous PGD2 in PTZ-induced seizures. H-PGDS-transgenic mice showed the elevated level of a urinary metabolite of PGD2, tetranor-PGDM, 3.3- and 2.8-fold higher than the wild-type littermates under the basal condition and after the PTZ administration, respectively, without significantly changing the urinary concentration of a PGE2-metabolite, tetranor-PGE2. The intensity of PTZ-induced seizures was decreased in H-PGDS-transgenic mice as evident by the increased seizure onset latency, and a decrease in total duration of generalized tonic-clonic seizures and a total number of EEG seizure spikes during the postictal period (84 sec, 17 sec, and 5.3/min, respectively), as compared to wild-type mice (53 sec, 24 sec, and 12.6/min, respectively). These results indicate that overproduction of endogenous PGD2 decreased PTZ-induces seizures.
Source: Neuroscience Letters - Category: Neuroscience Source Type: research