Brain anticonvulsant protection of mice given chronic carbamazepine under various fatty acid and magnesium diet conditions

作者：Pages Nicole; Maurois Pierre; Delplanque Bernadette; Bac Pierre; Vamecq Joseph^*

来源：Prostaglandins, Leukotrienes and Essential Fatty Acids, 2012, 87(2-3): 63-70.

DOI：10.1016/j.plefa.2012.06.002

• Polyunsatured fatty acids
• Alpha-linolenic acid (ALA)
• Eicosapentaenoic acid (EPA)
• Rapeseed oil
• Docosahexaenoic acid (DHA)
• Brain protection
• Magnesium deficiency
• Chemical seizures
• Electrical seizures
• Audiogenic seizures
• Anticonvulsant
• Carbamazepine
• Ap2
• Arachidonate signaling
• Phospholipase A2
• GABA(B) receptors
• NMDA

The anticonvulsant and mood stabilizer drug carbamazepine (CBZ) was evaluated for anti-seizure activity after drug pretreatment of young weaning mice given various oil-based diets. These diets had various mono-(MUFA) and poly-(PUFA) unsaturated fatty acid contents, were associated or not with magnesium deprivation, and were given over the entire experimental period (34 days). The diets included a commercial and three purified synthetic diets (n-6 PUFA, n-3 PUFA and MUFA-based chows containing 5% corn/sunflower oils 1:3, 5% rapeseed oil and 5% high oleic acid sunflower oil/sunflower oil 7:3, respectively). A 10-days CBZ treatment (50 mg/kg/day fragmented in two daily intraperitoneal injections of 25 mg/kg) was given 20 days after initiating diet administration and evaluations of mice was performed 4 days after arrest of CBZ in various seizure tests. In these conditions, CBZ pretreatment still exhibited anticonvulsant protection especially in magnesium-deficient animals. Ethosuximide (ESM)-like profiles under MUFA and n-3 PUFA diets and unusual GABA(A)ergic profile under n-6 PUFA diet in magnesium-deficiency dependent audiogenic seizures (MDDAS) test as well as protection against NMDA-induced seizures in all lipid (n-3 PUFA %26gt; MUFA and n-6 PUFA) diet conditions were observed in CBZ-pretreated mice. By highlighting ESM-like and anti-NMDA mechanisms previously induced by an n-3 PUFA diet, present CBZ anticonvulsant properties suggest brain protective targets common to CBZ and n-3 PUFAs.

• 出版日期2012-9