Somatostatin Release in the Hippocampus in the Kindling Model of Epilepsy

Abstract

Somatostatin biosynthesis in the hippocampus is activated during and following kindling epileptogenesis. The aim of this study was to investigate whether this phenomenon is associated with enhanced somatostatin release in vivo. Experiments have been run in awake, freely moving rats, implanted with a bipolar electrode in the right amygdala (for kindling stimulation), and with a recording electrode and a microdialysis probe in the left hippocampus. Basal somatostatin-like immunoreactivity (-LI) release was significantly greater in kindled than naive rats. In naive rats, a 2-min perfusion with 100 mM K ϩ did not affect behavior and EEG recordings and nonsignificantly increased somatostatin-LI release; a 10-min K ϩ perfusion evoked numerous wet dog shakes, electrical seizures (class 0; latency Х8 min, duration Х8 min), and somatostatin-LI release (Х350% of basal); and a single kindling after-discharge (4 Ϯ 3-s duration in the hippocampus) also evoked somatostatin-LI release (Х200% of basal). In kindled rats, a 2-min 100 mM K ϩ perfusion evoked hippocampal discharges in three of seven animals (latency Х2 min, mean duration Х1.5 min) and increased somatostatin-LI release (Х250% of basal); a 10-min K ϩ perfusion evoked behavioral seizures (class 1 to 5, latency Х4 min, mean duration Х12 min) with numerous wet dog shakes and robust somatostatin-LI release (Х350% of basal); and a kindling stimulation evoked generalized seizures (class 4 or 5, 77 Ϯ 15-s duration in the hippocampus) with remarkable somatostatin-LI release (Х300% of basal). These data demonstrate that hippocampal somatostatin release is increased in the kindling model in vivo. Key Words: Somatostatin-Hippocampus-Kindling-Microdialysis. J. Neurochem. 74, 2497Neurochem. 74, -2503Neurochem. 74, (2000.The biosynthesis of somatostatin appears to be altered in several "acute" seizure models (see Schwarzer et al., 1996) and in kindling, a gradual process of epileptogenesis considered to model certain aspects of human partial epilepsy (McNamara, 1984). Kindling is induced by the repeated application of an initially subconvulsive stimulus to a discrete brain area, which evokes a progressive seizure activity, culminating in generalized tonic-clonic convulsions (Goddard, 1967). Once established, this latent hyperexcitability is essentially permanent. An increase in preprosomatostatin mRNA and in somatostatin levels has been found in the hippocampus, the cortex, and the striatum during and following kindling epileptogenesis (Shinoda et al., 1989(Shinoda et al., , 1991Schwarzer et al., 1996), indicating an augmented peptide synthesis.An activation of somatostatin biosynthesis during kindling may translate into or depend on enhanced release of the peptide. However, somatostatin release studies conducted thus far have provided apparently conflicting results. Release of somatostatin has been reported to increase in hippocampal slices (Vezzani et al., 1992) but not in hippocampal synaptosomes (Simonato et al., 1998) taken from kindled rats. The aim of this stud...

Somatostatin: An endogenous antiepileptic

“…Baseline and K+ -induced SST release was significantly higher in hippocampal slices kindled rats vs. control rats (Vezzani et al, 1992). An in vivo study microdialysis study reported similar findings, i.e., an increase in both basal and K+ -stimulated release in hippocampus after kindling (Marti et al, 2000). Increased SST release following seizures would likely be protective (see below).…”

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

“…The cell bodies and horizontal dendrites of O-LM cells are located in the stratum oriens and provide inhibition to the distal dendrites of pyramidal cells in the stratum lacunosum-moleculare [34]. Somatostatin is released from hippocampal neurons after seizures [35] and its expression was enhanced by seizures in animal models [36]. However, a loss of somatostatin interneurons was found in the hilus in human temporal lobe epilepsy and in animal models of epilepsy while somatostatin usually remained in the Ammon´s horn even in sclerotic hippocampus [37,38].…”

The Effect of Octreotide on Kainate-Induced Wet Dog Shakes and Seizure Activity in Male and Female Rats

“…Because NOS and SS colocalize in the dentate hilus of rat hippocampus (Dun et al, 1994), and because the permissive role of NO on SS release are documented (Aguila, 1994;McCann et al, 1996), the behavioral effect of SS would be expected to be inversely related to NOS inhibition. In awake, freely moving rats, kindling epileptogenesis evoked WDS and SS release (Marti, Bregola, Morari, Gemignani, & Simonato, 2000), suggesting a compensatory mechanism.…”