First visualization of glutamate and GABA in neurones by immunocytochemistry

Storm‐Mathisen, Jon; Leknes, Alfhild Kristine; Bore, Anna Torbjørg; Vaaland, Jorunn Line; Edminson, Paul D.; Haug, Finn‐Mogens Šmejda; Ottersen, Ole Petter

doi:10.1038/301517a0

Cited by 861 publications

(289 citation statements)

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“…First, malonate was shown primarily to enter neurons, as could be seen from the higher specific activity of glutamate than of glutamine after injection of radiolabeled malonate (Hassel et al, 2002;Van den Berg et al, 1969). Second, formation of glutamate from radiolabeled glucose, a predominantly neuronal process (Hassel et al, 1997;Storm-Mathisen et al, 1983), was severely reduced in malonate-treated striatum, whereas the formation of glutamine, a strictly glial reaction in the brain (Martinez-Hernandez et al, 1977), was unaffected. A loss of ATP leads to a loss of ion gradients and hence to a reversal of glutamate transporters in ATP-depleted neurons (Erecinska and Nelson, 1994).…”

Section: Long-term Vpa Treatment May Be Neuroprotective In Striatummentioning

confidence: 99%

“…Glutamine synthetase is an ATP-dependent enzyme that is expressed in glia but not in neurons (Martinez-Hernandez et al, 1977). 14 CLabeling of glutamine was unaffected by malonate treatment, whereas 14 C-labeling of glutamate was reduced by 60% (Table 1), suggesting inhibition of the tricarboxylic acid cycle in neurons, in which glutamate is concentrated (Storm-Mathisen et al, 1983).…”

Section: Glial Formation Of Glutamine and Uptake Of Glutamate Proceedmentioning

confidence: 99%

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Valproate is Neuroprotective against Malonate Toxicity in Rat Striatum: An Association with Augmentation of High-Affinity Glutamate Uptake

Morland

Boldingh

Iversen

et al. 2004

J Cereb Blood Flow Metab

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Summary:The antiepileptic drug valproate (VPA) may be neuroprotective. We treated rats with VPA for 14 days (300 mg/kg twice daily) before intrastriatal injection of 1.5 mol (1 M) of the succinate dehydrogenase inhibitor malonate. VPAtreated animals developed smaller lesions than control animals: 10 ± 2 mm 3 versus 26 ± 8 mm 3 (means ± SD; P ‫ס‬ 10 −4 ). Injection of NaCl that was equiosmolar with 1 M malonate caused lesions of only 1.2 ± 0.4 mm 3 in control animals, whereas physiologic saline produced no lesion. VPA pretreatment reduced the malonate-induced extracellular accumulation of glutamate. This effect paralleled an increase in the striatal level of the glutamate transporter GLT, which augmented highaffinity glutamate uptake by 25%, as determined from the uptake of [ 3 H] glutamate into striatal proteoliposomes. Malonate caused a 76% reduction in striatal adenosine triphosphate (ATP) content, but the glial, ATP-dependent formation of glutamine from radiolabeled glucose or glutamate was intact, indicating that glial ATP production supported uptake of glutamate. Striatal levels of HSP-70 and fos were reduced, and the levels of bcl-2 and phosphorylated extracellular signalregulated kinase remained unaffected, but histone acetylation was increased by VPA treatment. The results suggest that augmentation of glutamate uptake may contribute importantly to VPA-mediated neuroprotection in striatum.

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Section: Long-term Vpa Treatment May Be Neuroprotective In Striatummentioning

confidence: 99%

Section: Glial Formation Of Glutamine and Uptake Of Glutamate Proceedmentioning

confidence: 99%

Valproate is Neuroprotective against Malonate Toxicity in Rat Striatum: An Association with Augmentation of High-Affinity Glutamate Uptake

Morland

Boldingh

Iversen

et al. 2004

J Cereb Blood Flow Metab

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“…In the molecular layer, the glutamatergic synapses are densely distributed in the neuropil, mainly consisting of terminals of parallel fibres and, to a lesser extent, of climbing fibres on the dendritic trees of Purkinje neurons [35-40]. In the same layer, GABAergic synapses are distributed throughout the neuropil and consist mainly of synapses of stellate neuron axon terminals on dendrite trees of Purkinje neurons [41-43].…”

Section: Introductionmentioning

confidence: 99%

“…In the Purkinje neuron layer, only GABAergic synapses are present, concentrated at the deep pole of the body of Purkinje neurons and formed by terminals of basket neuron axons [42-44]. In the granular layer, glutamatergic synapses and GABAergic synapses are both located in the neuropil regions scattered among granules (islands of Held), consisting of multiple synapses (glomeruli) established by glutamatergic terminals of mossy fibres and of axons of unipolar brush neurons [35-38,45] and GABAergic axon terminals of Golgi, candelabrum and Lugaro neurons [44,46,47], on granule dendrites.…”

Section: Introductionmentioning

confidence: 99%

VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

et al. 2011

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BackgroundThe aim of this study was to assess the distribution of key SNARE proteins in glutamatergic and GABAergic synapses of the adult rat cerebellar cortex using light microscopy immunohistochemical techniques. Analysis was made of co-localizations of vGluT-1 and vGluT-2, vesicular transporters of glutamate and markers of glutamatergic synapses, or GAD, the GABA synthetic enzyme and marker of GABAergic synapses, with VAMP-2, SNAP-25A/B and syntaxin-1.ResultsThe examined SNARE proteins were found to be diffusely expressed in glutamatergic synapses, whereas they were rarely observed in GABAergic synapses. However, among glutamatergic synapses, subpopulations which did not contain VAMP-2, SNAP-25A/B and syntaxin-1 were detected. They included virtually all the synapses established by terminals of climbing fibres (immunoreactive for vGluT-2) and some synapses established by terminals of parallel and mossy fibres (immunoreactive for vGluT-1, and for vGluT-1 and 2, respectively). The only GABA synapses expressing the SNARE proteins studied were the synapses established by axon terminals of basket neurons.ConclusionThe present study supplies a detailed morphological description of VAMP-2, SNAP-25A/B and syntaxin-1 in the different types of glutamatergic and GABAergic synapses of the rat cerebellar cortex. The examined SNARE proteins characterize most of glutamatergic synapses and only one type of GABAergic synapses. In the subpopulations of glutamatergic and GABAergic synapses lacking the SNARE protein isoforms examined, alternative mechanisms for regulating trafficking of synaptic vesicles may be hypothesized, possibly mediated by different isoforms or homologous proteins.

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“…of Molecular Neurobiology, Burke Rehabilation Center, 785 Mamaroneck, White Plains, NY 10605) was produced in rats by previously described methods (Lauder et al, 1986). Sprague-Dawley rats (Hilltop Lab Animals, Inc., PA) were immunized with GABA-glutaraldehyde-hemocyanin conjugates, prepared by the method of Storm-Mathisen et al (1983). In tests for specificity, the immunoreactivity visualized in sections of tissue was not blocked by 10 mM unconjugated GABA or 100 PM BSA-conjugated glutamate, /3-alanine, or taurine but was completely abolished by preincubation with 10 PM GABA-BSA (Lauder et al, 1986).…”

Section: Methodsmentioning

confidence: 99%

GABAergic neurons in the rat hippocampal formation: ultrastructure and synaptic relationships with catecholaminergic terminals

Milner

Bacon

1989

J. Neurosci.

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Numerous studies indicate that gamma-aminobutyric acid (GABA) can either hyperpolarize or depolarize hippocampal pyramidal and granule cells. While the inhibitory action of GABA may occur directly on these cells, the excitatory action may be mediated by interactions of GABAergic neurons with each other or with catecholaminergic afferents. We sought to examine the cellular basis for these interactions and their relative frequency. Thus, the ultrastructural morphology of GABAergic neurons and their relation to terminals exhibiting immunoreactivity for the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH) were examined in the rat hippocampal formation using combined immunoautoradiographic and peroxidase-antiperoxidase labeling methods. By light microscopy, GABAergic perikarya and processes codistributed most noticeably with TH-containing processes in the hilus of the dentate gyrus (DG) and in strata lucidum, radiatum, and lacunosum-moleculare of the CA3 region of the hippocampus. Thus, these regions were examined further by electron microscopy. In the ultrastructural analysis, GABA-like immunoreactivity (GABA-LI) was detected in neuronal perikarya, dendrites, axons, and axon terminals. The GABA-containing perikarya were large, ovoid (20–40 microns in diameter), and contained abundant cytoplasm and an indented nucleus with one nucleolus. Synaptic junctions on the perikarya and dendrites with GABA-LI were both symmetric and asymmetric. Approximately equal numbers of TH-labeled terminals (19% of 133 in DG; 39% of 26 in CA3) and GABA-containing terminals (19% DG, 15% CA3) formed synapses with GABA-labeled perikarya. The remainder of the presynaptic terminals (62% DG, 46% CA3) were unlabeled, i.e., contained unidentified transmitters. Terminals with GABA-LI (0.5–1.6 microns) contained numerous small clear vesicles and from 0 to 2 large dense-core vesicles. The types of associations formed by terminals with GABA-LI were remarkably similar in the DG and hippocampus proper despite differences in intrinsic cell type and function. Terminals with GABA-LI formed associations with unlabeled perikarya and dendrites (24% of 151 in DG, 25% of 75 in CA3) and synapses with GABA-containing perikarya and dendrites (18% DG, 5% CA3). Additionally, GABAergic terminals converged upon the same perikarya or dendrite as a TH-containing terminal (15% DG, 21% CA3) and were in direct apposition to TH-labeled terminals (19% DG, 20% CA3). The remaining GABAergic terminals (24% DG, 28% CA3) were without any apparent synaptic relations. In both the DG and CA3, the junctions formed by GABAergic terminals were symmetric. Terminals showing colocalization of GABA-LI and TH-I were also detected although rarely.(ABSTRACT TRUNCATED AT 400 WORDS)

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First visualization of glutamate and GABA in neurones by immunocytochemistry

Cited by 861 publications

References 12 publications

Valproate is Neuroprotective against Malonate Toxicity in Rat Striatum: An Association with Augmentation of High-Affinity Glutamate Uptake

Valproate is Neuroprotective against Malonate Toxicity in Rat Striatum: An Association with Augmentation of High-Affinity Glutamate Uptake

VAMP-2, SNAP-25A/B and syntaxin-1 in glutamatergic and GABAergic synapses of the rat cerebellar cortex

GABAergic neurons in the rat hippocampal formation: ultrastructure and synaptic relationships with catecholaminergic terminals

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