Time‐ and Region‐Specific Variations in Somatostatin Release Following Amygdala Kindling in the Rat

Simonato, Michele; Bregola, Gianni; Beani, L.; Vezzani, Annamaria; Sala, Roberta; Raiteri, Maurizio; Bonanno, Giambattista

doi:10.1046/j.1471-4159.1998.70010252.x

Cited by 7 publications

(7 citation statements)

References 30 publications

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“…In the current report, the increase of GAD 65 -IR, as well as CCK-IR, puncta detected 96 h after picrotoxin infusion is likely to reflect slowly evolving changes within hippocampal circuitry. Similar delayed effects have been shown using other experimental paradigms (e.g., Schwarzer and Sperk, 1995;Zhang et al, 1996;Simonato et al, 1998;Bouilleret et al, 2000). An increase in GAD 65 -and CCK-IR terminals could be parsimoniously explained by a direct and sustained increase of activation of intrinsic GABAergic neurons in the hippocampus by amygdalar afferents that results in a sprouting and/or increased size of GABAergic terminals.…”

Section: Changes In Terminalssupporting

confidence: 74%

Long‐term effects of amygdala GABA receptor blockade on specific subpopulations of hippocampal interneurons

et al. 2004

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Growing evidence indicates that the amygdala modulates hippocampal functions. To test the hypothesis that this modulation may involve long-lasting effects on interneuronal networks in the hippocampus, changes in the expression of neurochemical markers specific for different interneuronal subpopulations were assessed in adult rats 96 h following acute infusion of low doses of the GABAA receptor antagonist picrotoxin into the amygdala. The numerical density (Nd) of somata showing immunoreactivity (IR) for parvalbumin (PVB) was decreased in dentate gyrus (DG) and the CA4-2 region, while that of calretinin (CR)-IR was decreased in DG and CA2. The Nd of calbindin D28k (CB)-IR somata was decreased in CA3-2. The densities of axon terminals arising from PVB-IR and cholecystokinin (CCK)-IR basket neurons were also altered, with those of CCK-IR terminals increased across all sectors, while PVB-IR terminals were decreased only in the CA region. Increases in CCK-IR terminals were paralleled by increases of terminals with IR for the 65-kD isoform of glutamate decarboxylase (GAD65). Mixed-effects statistical models, adapted specifically for these analyses, indicated that perturbations of amygdalar inputs to the hippocampus significantly alter the drive that hippocampal PVB-, CR-, and CB-IR neurons within the dentate gyrus/CA4 region exercise on CCK-IR terminals within the same region as well as in CA3-1. These results suggest that amygdalar modulation of specific neuronal subpopulations may induce lasting and far-reaching changes in the hippocampus during normal functioning, as well as in diseases involving a disruption of amygdalar activity. In particular, changes in specific interneuronal markers within selective hippocampal sectors detected in the present results are strikingly similar to those reported in this region in schizophrenia. These similarities suggest that, in this disease, a disruption of GABAergic transmission within the amygdala may play a significant role in the induction of abnormalities in the hippocampus.

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Section: Changes In Terminalssupporting

confidence: 74%

Long‐term effects of amygdala GABA receptor blockade on specific subpopulations of hippocampal interneurons

et al. 2004

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“…Interestingly, as discussed above for the basal release, in vivo (present study) and slice (Vezzani et al, 1992) studies show greater somatostatin‐LI stimulation‐evoked release in the kindled than the control hippocampus; this, however, does not apply to isolated terminals (synaptosomes; Simonato et al, 1998). Again, the involvement of transsynaptic excitatory effects (lost in the synaptosomal preparation) may explain this discrepancy, and glutamate, because of the reasons discussed above and because it is phasically released during seizures (During and Spencer, 1993), is likely to play a leading role.…”

Section: Discussionsupporting

confidence: 47%

“…One interesting finding of this study is that basal (spontaneous) somatostatin‐LI release in the hippocampus is highly increased in kindled rats. Thus, in the kindled, as compared with control, hippocampus, somatostatin‐LI spontaneous release is increased by approximately twofold both in vivo (present study) and in slices (Vezzani et al, 1992) but not in isolated terminals (synaptosomes; Simonato et al, 1998). Furthermore, in the kindled hippocampus, somatostatin‐LI and preprosomatostatin mRNA levels are increased in the interneurons of the polymorphic cell layer of the hilus and of the stratum oriens of CA1 (Bendotti et al, 1993; Schwarzer et al, 1996); somatostatin‐LI content in tissue homogenates is also significantly increased (Vezzani et al, 1992); and at the level of the nerve terminals, somatostatin‐LI levels are elevated in a subset of fibers (Wanscher et al, 1990; Schwarzer et al, 1995, 1996) but not in all somatostatinergic terminals, as indicated by the lack of significant changes in synaptosomes isolated from the whole hippocampus (Simonato et al, 1998).…”

Section: Discussionmentioning

confidence: 43%

“…Thus, the kindled state brings about an activation of the biosynthesis of somatostatin, which, however, does not appear to be constantly associated with accumulation of the peptide in the nerve terminals. Furthermore, it is likely that the increased release of somatostatin‐LI observed in kindled slices and in vivo depends on indirect transsynaptic effects, because somatostatin‐LI release from isolated terminals (synaptosomes) is unchanged in kindled rats (Simonato et al, 1998). Taken together, these observations suggest that an up‐regulated excitatory input may tonically activate somatostatin neurons (and increase somatostatin release) in the kindled hippocampus; as a consequence, this may cause an increase in the biosynthesis of the peptide, but the newly synthesized somatostatin may not always accumulate in the nerve terminals due to the tonic stimulation of release.…”

Section: Discussionmentioning

confidence: 99%

“…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 study was to attempt to shed light on this topic by evaluating somatostatin release from the kindled hippocampus in vivo.…”

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confidence: 99%

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Somatostatin Release in the Hippocampus in the Kindling Model of Epilepsy

Marti¹,

Bregola²,

Morari³

et al. 2000

Journal of Neurochemistry

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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...

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Adeno-associated viral vector-mediated preprosomatostatin expression suppresses induced seizures in kindled rats

et al. 2017

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Somatostatin is expressed widely in the hippocampus and notably in hilar GABAergic neurons that are vulnerable to seizure neuropathology in chronic temporal lobe epilepsy. We previously demonstrated that sustained bilateral preprosomatostatin (preproSST) expression in the hippocampus prevents the development of generalized seizures in the amygdala kindling model of temporal lobe epilepsy. Here we tested whether sustained preproSST expression is anticonvulsant in rats already kindled to high-grade seizures. Rats were kindled until they exhibited 3 consecutive Racine Grade 5 seizures before adeno-associated virus serotype 5 (AAV5) vector driving either eGFP (AAV5-CBa-eGFP) or preproSST and eGFP (AAV5-CBa-preproSST-eGFP) expression was injected bilaterally into the hippocampal dentate gyrus and CA1 region. Retested 3 weeks later, rats that received control vector (AAV5-CBa-eGFP) continued to exhibit high-grade seizures whereas 6/13 rats that received preproSST vector (AAV5-CBa-preproSST-eGFP) were seizure-free. Of these rats, 5/6 remained seizure-free after repeated stimulation sessions and when the stimulation current was increased. These results suggest that vector-mediated expression of preproSST may be a viable therapeutic strategy for temporal lobe epilepsy.

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Time‐ and Region‐Specific Variations in Somatostatin Release Following Amygdala Kindling in the Rat

Cited by 7 publications

References 30 publications

Long‐term effects of amygdala GABA receptor blockade on specific subpopulations of hippocampal interneurons

Long‐term effects of amygdala GABA receptor blockade on specific subpopulations of hippocampal interneurons

Somatostatin Release in the Hippocampus in the Kindling Model of Epilepsy

Adeno-associated viral vector-mediated preprosomatostatin expression suppresses induced seizures in kindled rats

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