Dissociations between Kindling and Mossy Fiber Sprouting

Corcoran, Michael E.; Armitage, Lisa L.; Hannesson, Darren K.; Jenkins, Elaine M.; Mohapel, Paul

doi:10.1007/978-1-4615-5375-5_16

Cited by 5 publications

(1 citation statement)

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“…Moreover, Sloviter (45), who first demonstrated signs of excitability before sprouting, suggested that the mossy fibers reestablish the recurrent inhibition that is lost at the beginning of the stimulation procedure, or regulate AD but not the development of convulsive seizures. Mossy fiber sprouting is not a prerequisite for, and could be a consequence of, the high‐frequency ictal discharge that is the hallmark of kindling, rather than a causal mechanism in kindling (46). Taken together, this evidence suggests that deficiency of DGKε could affect the progression and spread of hippocampal hyperexcitability.…”

Section: Discussionmentioning

confidence: 99%

Diacylglycerol Kinase Epsilon Modulates Rapid Kindling Epileptogenesis

Musto

Bazán

2006

Epilepsia

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Summary:Purpose: Diacylglycerol kinase epsilon (DGK ) regulates seizure susceptibility and long-term potentiation through arachidonoyl-inositol lipid signaling. We studied the significance of arachidonoyl-diacylglycerol (20:4 DAG) in epileptogenesis in DGK -deficient mice undergoing rapid kindling epileptogenesis.Methods: Tripolar electrode units were implanted in right dorsal hippocampi of male DGK +/+ and DGK −/− mice. Ten days after surgery, kindling was achieved by stimulating 6 times daily for 4 days with a subconvulsive electrical stimulation (10-s train of 50-Hz biphasic pulses, 75-200 μA amplitude) at 30-min intervals. After 1 week, mice were rekindled. EEGs were recorded and analyzed to characterize epileptogenic events as spikes, sharp waves, or abnormal amplitudes and rhythms. Right hippocampi were analyzed by histology [Timm's staining, neuropeptide Y (NPY) and glial fibrillary acidic protein immunoreactivity], and for DNA fragmentation (TUNEL).Results: DGK −/− mice had significantly fewer motor seizure and epileptic events compared with DGK +/+ mice from the second day of stimulation. These differences were maintained during rekindling. DGK −/− mice also exhibited lowamplitude spike-wave complexes, short spreading depression, and predominant lower-frequency (1-4 Hz) bands throughout stimulation, whereas DGK +/+ mice exhibited increased highfrequency bands (4-8 Hz; 8-15 Hz) from the second day of stimulation, as determined by power spectral analysis. DGK −/− mice displayed no sprouting in the supragranular area or NPY inmunoreactivity in the hilus and had weak astrocyte reactivation in all hippocampal areas. No TUNEL-positive cells were detected in any group of mice.Conclusions: DGK modulates kindling epileptogenesis through inositol lipid signaling. Because arachidonatecontaining diacylglycerol phosphorylation to phosphatidic acid is selectively blocked in DGK −/− mice, we postulate that the shortage of arachidonoyl-moiety inositol lipids and/or the messengers derived thereof is a key signaling event in epileptogenesis. Key Words: Diacylglycerol kinase-Kindling epileptogenesis-Inositol lipid signaling-Hippocampus.Partial complex seizure with secondary generalized seizure is one of the semiologic characteristics of mesial temporal lobe epilepsy (MTLE). In most cases, MTLE progresses with severe recurrence of seizures, becomes refractory to antiepileptic drugs (AEDs), and is related to certain mental and learning disabilities and psychosocial problems (1).Abnormal electrophysiologic responses through different mechanisms (abnormal excitation, enhanced synchronization, less frequency adaptation, diminutions of feedforward inhibition, abnormal burst, and paroxysmal firing) were found in hippocampal regions from patients who had MTLE (2). Excitatory glutamatergic signaling is one of the mechanisms proposed to trigger paroxysm shift depolarization (PSD), characterized as spikes that correlate with Accepted August 18, 2005. Address correspondence and reprint requests to Dr. N. G. Bazan at LSU Neuroscience ...

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Section: Discussionmentioning

confidence: 99%