Indispensable amino acid deficiency and increased seizure susceptibility in rats

Abstract

Repeated subthreshold stimulation of limbic brain areas increases seizure susceptibility in experimental models of epilepsy. In addition, acute dietary indispensable amino acid (IAA) deficiency activates the anterior piriform cortex (APC), a seizure-prone limbic brain area in the rat. Based on these two findings, we hypothesized that activation of the APC by chronic exposure to IAA-deficient diets might increase seizure susceptibility. Several nonessential amino acid neurotransmitters are important in seizures, but deficiencies of nontransmitter IAAs have not been well studied in seizure models. In four trials, we made injections of pentylenetetrazole intraperitoneally or of bicuculline into the APC in histidine-, isoleucine-, or threonine-deficient rats and controls. Increased susceptibility to seizures in the deficient animals was observed as increased severity of the seizures, decreased threshold for the dose of the chemostimulant and time to seizure, or a combination thereof. Pair-fed controls showed that this effect was not due to an energy deficit. This novel but robust finding suggests that IAA deficiency may increase vulnerability to seizures by repeated activation of the APC.

Malnutrition Increases Dentate Granule Cell Proliferation in Immature Rats After Status Epilepticus

“…Nevertheless, the seizure susceptibility of P15 malnourished rats was not affected compared with that of P1S nourished rats. The discrepancy between our results and other studies may be attributable to differences in the malnutrition paradigm, the age of the rats at seizure testing (9)(10)(11)(12)(13)(14), or some specific feature of the seizure model we used. Seizure expression did not differ between the malnourished and nourished rats, and mortality after status epilepticus was low in both groups.…”

“…Several authors (9)(10)(11)(12)(13)(14) have described changes in seizure susceptibility in malnourished rats exposed to dif-…”

Effects of early malnutrition and nutritional rehabilitation in rats

“…Desnutrição e epilepsia são problemas prevalentes em países em desenvolvimento, sendo uma relação causaefeito sugerida em estudos com modelo animal [4][5][6][7][8] . Até o presente momento, nenhum estudo clínico demonstrou que a desnutrição per se aumenta o risco de epilepsia, entretanto, em estudo prévio, observamos uma tendência a maior incidência de epilepsia em crianças desnutridas 9 .…”

“…Estudos experimentais evidenciam que a desnutrição perinatal causa alterações permanentes, fisiológicas e morfológicas no SNC em desenvolvimento, além de diminuir o limiar para crises convulsivas [4][5][6][7][8] . Os efeitos da desnutrição intrauterina são particularmente severos no período de proliferação e crescimento neuronal, sendo enfatizada a susceptibilidade de determinadas estruturas do sistema nervoso central, como córtex, hipocampo e cerebelo 10,11 .…”

“…Os efeitos da desnutrição intrauterina são particularmente severos no período de proliferação e crescimento neuronal, sendo enfatizada a susceptibilidade de determinadas estruturas do sistema nervoso central, como córtex, hipocampo e cerebelo 10,11 . Alterações no EEG, córtex visual e sensorimotor também já foram descritas [4][5][6][7][8]12 . Deficiências específicas de nutrientes, tais como aminoácidos indispensáveis, ativam o córtex piriforme anterior, que é uma estrutura límbica bastante susceptível a crises em ratos, causando um aumento da severidade das crises e diminuição do limiar convulsivante 7 .…”