Spontaneous epileptiform seizures but increased resistance to kindled seizures in a mutant Sprague-Dawley rat (mf/mf).
Approximately 30% of a breeding colony of Sprague-Dawley rats homozygous for an autosomal recessive mutation mf ("mutilated foot") associated with a peripheral sensory neuropathy have been found unexpectedly to suffer spontaneous epileptiform attacks. Seizures ranged from brief episodes of compulsive running to tonic-clonic convulsions lasting for up to 30 s, recurring at intervals of hours or days. EEG recordings during seizures showed high-voltage 8-10 Hz spike trains that abated over the ensuing 1-2 min. Interictal records were usually normal. Twice-daily kindling of the amygdala (200 microA sinewave for 1.0 s) was unexpectedly ineffective. Most of the rats that had suffered spontaneous seizures failed to develop kindled afterdischarges, even after 30 kindling stimulations. Other mf rats developed prolonged high-amplitude kindled afterdischarges that were arrested at stage 2 and failed to evolve into convulsive seizures. Hippocampal dentate granule cells of kindled mf rats, stained for zinc by Timm's method, showed significantly less mossy fibre sprouting than wild-type Sprague-Dawley rats after the same number of kindled afterdischarges. A minority of the mf rats tested (2 of 14) kindled normally. Auditory stimulation (n = 23) or stroboscopic flicker (n = 14) failed to elicit seizures or running fits in any mf rat. Peripheral neuropathy corresponding to that in the mf rat, with resistance to kindling and diminished mossy fibre sprouting, have also been reported in transgenic mice with defective p75NGFR neurotrophin receptors. A homologous genetic defect in the rat could account for most of the features of the mf phenotype.
Herberg
L J
LJ
Experimental Psychology Laboratory, Institute of Neurology, London, UK.
Rose
I C
IC
Davison
F
F
Thom
M
M
Beckett
A
A
Scaravilli
F
F
D000161:Acoustic Stimulation; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000473:pathology; D004567:Electrodes, Implanted; D004569:Electroencephalography; D006624:Hippocampus / Q000473:pathology; D007696:Kindling, Neurologic / Q000235:genetics* / Q000502:physiology; D019599:Mossy Fibers, Hippocampal / Q000502:physiology; D009154:Mutation; D010775:Photic Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000235:genetics* / Q000473:pathology / Q000523:psychology