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Clozapine-induced reduction of glutamate transport in the frontal cortex is not mediated by GLAST and EAAC1
No full textExpression of Neurofilament Subunits at Neocortical Glutamatergic and GABAergic Synapses
No full textHeterogeneity of glutamatergic and GABAergic release machinery in cerebral cortex: analysis of synaptogyrin, vesicle-associated membrane protein, and syntaxin
No full textTo define whether cortical glutamatergic and GABAergic release machineries can be
differentiated on the basis of the nature and amount of proteins they express, we studied the degree
of co-localization of synaptogyrin (SGYR) 1 and 3, vesicle-associated membrane protein (VAMP)
1 and 2, syntaxin (STX) 1A and 1B in VGLUT1-, VGLUT2- and VGAT-positive (+) puncta and
synaptic vesicles in the rat cerebral cortex.
Co-localization studies showed that SGYR1 and 3 were expressed in about 90% of
VGLUT1+, 70% of VGLUT2+ and 80% of VGAT+ puncta; VAMP1 was expressed in
approximately 45% of VGLUT1+, 55% of VGLUT2+, and 80% of VGAT+ puncta; VAMP2 in
about 95% of VGLUT1+, 75% of VGLUT2+, and 80% of VGAT+ puncta; STX1A in about 65% of
VGLUT1+, 30% of VGLUT2+, and 3% of VGAT+ puncta, and STX1B in approximately 45% of
VGLUT1+, 35% of VGLUT2+, and 70% of VGAT+ puncta. Immunoisolation studies showed that
while SXT1A was completely segregated and virtually absent from VGAT synaptic vesicles,
STX1B, VAMP1/VAMP2, SGYR1/SGYR3 showed a similar pattern with the highest expression in
VGLUT1 immunoisolated vesicles and the lowest in VGAT immunoisolated vesicles. Moreover,
we studied the localization of STX1B at the electron microscope and found that a population of
axon terminals forming symmetric synapses were STX1B-positive.
These results extend our previous observations on the differential expression of presynaptic
proteins involved in neurotransmitter release in GABAergic and glutamatergic terminals and
indicate that heterogeneity of glutamatergic and GABAergic release machinery can be contributed
by both the presence or absence of a given protein in a nerve terminal and the amount of protein
expressed by synaptic vesicle
Clozapine up-regulates the expression of the vesicular GABA transporter (VGAT) in rat cerebral cortex
No full textLevetiracetam Affects Differentially Presynaptic Proteins in Rat Cerebral Cortex
Full text linkPresynaptic proteins are potential therapeutic targets for epilepsy and other neurological diseases. We tested the hypothesis that chronic treatment with the SV2A ligand levetiracetam affects the expression of other presynaptic proteins. Results showed that in rat neocortex no significant difference was detected in SV2A protein levels in levetiracetam treated animals compared to controls, whereas levetiracetam post-transcriptionally decreased several vesicular proteins and increased LRRK2, without any change in mRNA levels. Analysis of SV2A interactome indicates that the presynaptic proteins regulation induced by levetiracetam reported here is mediated by this interactome, and suggests that LRRK2 plays a role in forging the pattern of effects
Acute phencyclidine administration reduces extracellular glutamate levels and the expression of synaptophysin and SNAP-25 in rat frontal cortex
No full textBragina L, Bonifacino T, Bassi S, Milanese M, Bonanno G and Conti F (2015). Differential expression of metabotropic glutamate and GABA receptors at neocortical glutamatergic and GABAergic axon terminals.
No full textMetabotropic glutamate (Glu) receptors (mGluRs) and GABAB receptors are highly expressed at presynaptic sites. To verify the possibility that the two classes of metabotropic receptors contribute to axon terminals heterogeneity, we studied the localization of mGluR1α, mGluR5, mGluR2/3, mGluR7, and GABAB1 in VGLUT1-, VGLUT2-, and VGAT- positive terminals in the cerebral cortex of adult rats. VGLUT1-positive puncta expressed mGluR1α (∼5%), mGluR5 (∼6%), mGluR2/3 (∼22%), mGluR7 (∼17%), and GABAB1 (∼40%); VGLUT2-positive terminals expressed mGluR1α (∼10%), mGluR5 (∼11%), mGluR2/3 (∼20%), mGluR7 (∼28%), and GABAB1 (∼25%); whereas VGAT-positive puncta expressed mGluR1α (∼27%), mGluR5 (∼24%), mGluR2/3 (∼38%), mGluR7 (∼31%), and GABAB1 (∼19%). Control experiments ruled out the possibility that postsynaptic mGluRs and GABAB1 might have significantly biased our results. We also performed functional assays in synaptosomal preparations, and showed that all agonists modify Glu and GABA levels, which return to baseline upon exposure to antagonists. Overall, these findings indicate that mGluR1α, mGluR5, mGluR2/3, mGluR7, and GABAB1 expression differ significantly between glutamatergic and GABAergic axon terminals, and that the robust expression of heteroreceptors may contribute to the homeostatic regulation of the balance between excitation and inhibition
Heterogeneity of glutamatergic and GABAergic release machineries in cerebral cortex
No full textWe investigated whether cortical glutamatergic and GABAergic release machineries can be
differentiated on the basis of the proteins they express, by studying the degree of co-localization of
synapsin (SYN) I and II, synaptophysin (SYP) I and II, SNAP-25 and SNAP-23 in VGLUT1-,
VGLUT2- and VGAT-positive (+) puncta in the rat cerebral cortex.
Co-localization studies showed that SYNI and II were expressed in ~90% of VGLUT1+,
~30% of VGLUT2+ and 30-50% of VGAT+ puncta; SYPI was expressed in ~95% of VGLUT1+,
30% of VGLUT2+, and 45% of VGAT+ puncta; SYPII in ~7% of VGLUT1+, 3% of VGLUT2+,
and 20% of VGAT+ puncta; SNAP-25 in ~94% of VGLUT1+, 5% of VGLUT2+, and 1% of
VGAT+ puncta, and SNAP-23 in ~3% of VGLUT1+, 86% of VGLUT2+, and 22% of VGAT+
puncta. Since SYPI, which is considered ubiquitous, was expressed in about half of GABAergic
axon terminals, we studied its localization electron microscopically and in immunoisolated synaptic
vesicles: these studies showed that ~30% of axon terminals forming symmetric synapses were
SYPI-negative, and that immunoisolated VGAT-positive synaptic vesicles were relatively depleted
of SYPI as compared to VGLUT1+ vesicles.
Overall, the present investigation shows that in the cerebral cortex of rats distinct
presynaptic proteins involved in neurotransmitter release are differentially expressed in GABAergic
and in the two major types of glutamatergic axon terminals in the cerebral cortex of rats
GLT-1 down-regulation induced by clozapine in rat frontal cortex is associated with synaptophysin up-regulation
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