Abstracts

Rationale: to compare the expression of NPY and its receptors NPYR1, NPYR2 and NPYR5 in mice hippocampus infected with Toxoplasma gondii [frequently associated with seizure] to those infected with Trypanosoma brucei [not associated with high incidence of seizure] and to compare similar expression between seizure-prone BALB/c and seizure-resistant C57Bl/6 [B6] mice infected with Trypanosoma brucei; and between inducible nitric oxide synthetase knock-out [iNOS-/-] B6 trypanosome infected and iNOS-/- uninfected B6 mice.Methods: 20 B6 and 24 BALB/c mice (8-12 weeks old) were infected with 2000 Trypanosoma brucei brucei [T.b.b.] and 4 animals were sacrificed, their hippocampus immediately dissected at 8, 21, 28, 33 days post-infection (dpi) for the B6 mice and at 10, 18, 26, 35 dpi for the BALB/c mice. Transcripts for NPY and its receptors were determined by real-time RT PCR from hippocampi dissected. Hippocampi were punched from 4 frozen BALB/c mice brain that were infected with Toxoplasma tachyzoites, and transcripts for NPY and its receptors similarly measured. Comparison of NPY, NPYR1 and NPYR2 expression along the dorsal hippocampus was made by immunohistochemistry using tyramide signal amplification (TSA) between the T.b.b. infected and control un-infected BALB/c mice. Similar expression was compared between 4 iNOS-/- T.b.b. infected B6 and uninfected iNOS-/- B6 mice. Susceptibility for seizure was serially checked by tail rotation in all mice.Results: T.b.b. infected B6 mice had expression of NPY, NPYR1, NPYR2 and NPYR5 in the early to intermediate dpi which leveled to be comparable to control un-infected ones at late dpi. T.b.b. infected BALB/c mice showed progressively increased expression of NPYR1 and NPYR5. Increased expression of NPY, NPYR1, NPYR2 and NPYR5 is seen in the toxoplasmosis infected BALB/c. The immunohistochemistry showed increased NPY expression, comparable NPYR1expression and increased NPYR2 expression in the late dpi samples of the BALB/c T.b.b. infected mice. iNOS-/- B6 mice had down-regulated NPY receptors, and were the only ones to develop seizures on the tail-rotation.Conclusions: Progressive increased expression of NPY receptors in the seizure-prone BALB/c mice models of trypanosomiasis and in the seizure-prone toxoplasmosis mice models, supports the protective role of NPY against seizure in neuroinflammation. iNOS maybe an important factor in the expression of NPY receptors.