-
[show abstract]
[hide abstract]
ABSTRACT: Neuronal loss and gliosis were detected in the rat hippocampus soon after unilateral intra-amygdala injection of kainate (KA) (2.5 nmol) while solid mossy fiber sprouting could be seen only fourteen days after this injection. Using this experimental model, we examined the metabotropic glutamate receptor (mGluR)-induced inositol phosphate (IP) formation in hippocampal synaptoneurosomes and slices. In synaptoneurosomes prepared from ipsilateral hippocampi fourteen days following injection, there were no significant changes in mGluR- and carbachol(CARB)-stimulated IPs syntheses when sham-operated and KA-injected animals were compared. In the corresponding hippocampal slices, significant increases of the mGluR responses mediated by ibotenate (IBO) and aminocyclopentane-trans-1,3-dicar☐ylate (t-ACPD) were noted after KA application. The net stimulation values respectively expressed in a pair-wise fashion for buffer-injected control and KA-treated animals were IBO: 1,947 ± 457 and 10,553 ± 1,242; t-ACPD: 1,557 ± 662 and 9,449 ± 2,251 dpm/mg protein respectively. Significantly augmented mGluR responses in hippocampal slices were also measured at 7,42 and 92 days after KA injection. There were, however, no significant increases in CARB-stimulated phosphoinositide hydrolysis in the hippocampal slices at all time-intervals after KA administration. These findings show that there are differences between the mGluR responses in hippocampal synaptoneurosome and slice preparations, suggesting the presence of two distinct populations of mGluR in each of these two models. The large specific increases in certain mGluR activities after KA-induced status epilepticus in hippocampal slices could represent one of the molecular mechanisms which underlie the profound morphological changes, in particular gliosis or mossy fiber sprouting, which follow the KA-induced status epilepticus.
Brain Research 06/1994; · 2.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The effect of postnatal age on phosphoinositide metabolism per se and on quisqualate-stimulated phosphoinositide metabolism was characterized in synaptoneurosomes prepared from nine different regions of the rat nervous system, namely the brainstem, cerebellum, cerebral cortex, colliculi, hippocampus, hypothalamus, olfactory bulb, spinal cord and striatum. In the hippocampus, striatum, cerebellum, cerebral cortex, brainstem, colliculus and spinal cord, the basal levels of inositol phosphate (inositol-1-phosphate+inositol-4,5-bisphosphate) formation were maximal two days after birth and declined steeply to steady-state levels from the age of 10 postnatal days. Similarly, in the olfactory bulb, basal inositol phosphate synthesis did not significantly change when measured during the period from postnatal day 10 to 42. The extent of [3H]-inositol labelling of phosphoinositides as a function of age presented similar profiles when measured in hippocampal, striatal, cerebellar and cerebral cortical synaptoneurosomes, i.e. maximal at perinatal ages and minimal at adult ages. In the hypothalamus, [3H]-inositol labelling of phosphoinositides showed an increase from postnatal day 12 to higher levels from postnatal days 14 to 18 subsequently followed by a dramatic increase from postnatal day 21 to 42. A similar developmental trend was also obtained for basal inositol phosphate synthesis.On the whole, four types of developmental profiles for quisqualate-stimulated inositol phosphate formation (expressed as the percentage of the basal level and as the difference between stimulated and basal levels of radioactive inositol phosphates) were obtained depending on the nervous system region studied. In the early, prenatally developed nervous system regions, namely the brainstem and the spinal cord, no postnatal stimulation peaks of quisqualate-induced inositol phosphate formation were recorded. This was also the case for the colliculi when the stimulation of IP formation was expressed as the difference in basal and stimulated levels of inositol phosphates. Secondly, in the olfactory bulb a region known to possess a continuous capacity for developmental plasticity both structurally and functionally during the first three weeks of postnatal development, a simultaneous sustained high level of quisqualate stimulation of phosphoinositide metabolism (fluctuating around 200% of the basal level) during the early postnatal period was evident. Thirdly, in regions of the central nervous system like the cerebellum, cerebral cortex, hippocampus and the striatum known to undergo intense developmental activity during the first two postnatal weeks, peaks of quisqualate-stimulated phosphoinositide metabolism were initially detected around the first week after birth in each of these brain areas. Finally, in the hypothalamus where structurally unique postnatal developmental processes are known to take place, quisqualate-induced inositol phosphate formation progressively increases with age to reach maxima at postnatal day 18. The transient increases in quisqualate responses in the cerebellum, hippocampus and striatum are probably specific to quisqualate since carbachol-stimulated phosphoinositide metabolism yielded different age-associated response patterns. Similar increases of carbachol- and quisqualate-mediated phosphoinositide hydrolysis were on the other hand assayed in cerebral cortical and hypothalamic synaptoneurosomes. EC50, values for quisqualate (the quisqualate concentration required to produce 50% of the maximal effect) at postnatal days 6 and 10 were not significantly different in each of four types of synaptoneurosomes: cerebellar, cerebral cortical, hippocampal and striatal. On the basis of these latter results, it was deduced that the peak of quisqualate-stimulated phosphoinositide metabolism does not materialize on the basis of changes in quisqualate metabotropic receptor affinity. In conclusion, the measurement of inositol phosphate formation in synaptoneurosomes prepared from different regions of the postnatally developing nervous system indicate that there is a temporal correlation between the increased activity of quisqualate-stimulated phosphoinositide metabolism mediated by specific metabotropic glutamate receptors and region-specific developmental events. This could suggest a key role for certain metabotropic glutamate receptors in the developmental plasticity of the nervous system.
International Journal of Developmental Neuroscience.
-
[show abstract]
[hide abstract]
ABSTRACT: The action of excitatory amino acids (EAA) on inositol phosphates (IPs) synthesis was examined in forebrain synaptoneurosomes of Long Evans rats (6–9 days old). Glutamate (GLU) (EC50: 23 μM) and quisqualate (QA) (EC50: 0.12 μM) enhanced IPs turnover. N-methyl-D-aspartate (NMDA) and kainate (KA) were less potent. The EAA-elicited IPs response was not blocked by tetrodotoxin (2 μM) or by the absence of Ca2+. This suggests that the activation of EAA receptors stimulates directly the phosphodiesterase responsible for phosphoinositide breakdown. The three main agonists (QA, KA and NMDA) tested in pairs, induced additive responses on IPs accumulation. In synaptoneurosomes prepared from adult rat, the relative responses to QA and GLU were dramatically reduced, whereas those to KA and NMDA remained unchanged. We concluded that GLU stimulates IPs formation mainly via a QA-like receptor subtype (AA2). This stimulation is transient and could play a key role during synaptogenesis. GLU also enhanced IPs accumulation via other receptor subtypes (probably of the NMDA- or AA1-like class).
European Journal of Pharmacology.
