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Fat‐1 transgenic mice endogenously synthesizing high levels of n−3 PUFA are resistant to pentylenetetrazol induced seizures
Author(s) -
Taha Ameer Y.,
Hout Pedro SP,
Lopez Sandra R,
Prayitno Nita R,
Kang Jing X,
Burnham W McIntyre,
Ma David WL
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a322-c
Subject(s) - pentylenetetrazol , polyunsaturated fatty acid , epilepsy , anticonvulsant , endocrinology , medicine , biology , biochemistry , fatty acid , psychiatry
Epilepsy is a serious neurological disorder which is characterized by spontaneous, recurrent seizures. Current medications have side effects including weight gain, fatigue and sedation. Omega‐3 (n−3) polyunsaturated fatty acids (PUFA), derived from marine fish oils, have been considered as an alternative treatment for patients with epilepsy. Accordingly, we hypothesized that enrichment of brain lipids with n−3 PUFA would inhibit the epileptic‐like seizures induced by pentylenetetrazol (PTZ). We demonstrate that the increased levels of n−3 PUFA in brain phospholipids of male and female transgenic Fat‐1 mice, which are capable of de novo synthesis of n−3 PUFA from n−6 PUFA, results in increased latency to seizure onset in males only (P<0.05 by 2‐way analysis of variance) . Latency to seizure onset was ~2‐fold longer in male Fat‐1 mice, as compared to male controls. Although not significant, the percentage of male and female mice that survived following the PTZ injection was also higher in Fat‐1 mice, as compared to controls (P=0.08 by chi‐squared test). These findings suggest that n−3 PUFA have anticonvulsant properties and would be potentially useful in the treatment of epilepsy.