Indispensable amino acid deficiency and increased seizure susceptibility in rats.
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.
Gietzen
D W
DW
Department of Veterinary Anatomy, Physiology, and Cell Biology, University of California, Davis 95616, USA.
Dixon
K D
KD
Truong
B G
BG
Jones
A C
AC
Barrett
J A
JA
Washburn
D S
DS
D000596:Amino Acids / Q000172:deficiency*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004056:Differential Threshold; D004198:Disease Susceptibility; D004334:Drug Administration Schedule; D006639:Histidine / Q000172:deficiency; D007267:Injections; D007274:Injections, Intraperitoneal; D007532:Isoleucine / Q000172:deficiency; D008032:Limbic System / Q000187:drug effects / Q000502:physiology; D008297:Male; D009833:Olfactory Pathways / Q000187:drug effects / Q000502:physiology; D010433:Pentylenetetrazole / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced*; D013912:Threonine / Q000172:deficiency
D000596:Amino Acids; D007532:Isoleucine; D013912:Threonine; D006639:Histidine; D010433:Pentylenetetrazole; D001640:Bicuculline