Changes in the Amino Acid Content of Nerve Endings (Synaptosomes) Induced by Drugs that Alter the Metabolism of Glutamate and γ‐Aminobutyric Acid

Geddes, James W.; Wood, J. D.

doi:10.1111/j.1471-4159.1984.tb09691.x

Cited by 128 publications

(63 citation statements)

References 20 publications

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“…After the precipitated protein was sedimented by centrifugation, the extracts were neutralized with 1 M KOH, and potassium perchlorate was spun down. Aliquots of the extracts were derivatized automatically with o-phthalaldehyde (Geddes and Wood, 1984) in an automatic sampler (Waters, Milford, MA). Twenty microliters of the sample were injected automatically into a HPLC system.…”

Section: Methodsmentioning

confidence: 99%

Functional Reorganization of Visual Cortex Maps after Ischemic Lesions Is Accompanied by Changes in Expression of Cytoskeletal Proteins and NMDA and GABA_AReceptor Subunits

Zepeda

Sengpiel

Guagnelli³

et al. 2004

J. Neurosci.

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Reorganization of cortical representations after focal visual cortex lesions has been documented. It has been suggested that functional reorganization may rely on cellular mechanisms involving modifications in the excitatory/inhibitory neurotransmission balance and on morphological changes of neurons peripheral to the lesion. We explored functional reorganization of cortical retinotopic maps after a focal ischemic lesion in primary visual cortex of kittens using optical imaging of intrinsic signals. After 1, 2, and 5 weeks postlesion (wPL), we addressed whether functional reorganization correlated in time with changes in the expression of MAP-2, GAP-43, GFAP, GABA A receptor subunit ␣1 (GABA A ␣1), subunit 1 of the NMDA receptor (NMDAR1), and in neurotransmitter levels at the border of the lesion. Our results show that: (1) retinotopic maps reorganize with time after an ischemic lesion; (2) MAP-2 levels increase gradually from 1wPL to 5wPL; (3) MAP-2 upregulation is associated with an increase in dendritic-like structures surrounding the lesion and a decrease in GFAP-positive cells; (4) GAP-43 levels reach the highest point at 2wPL; (5) NMDAR1 and glutamate contents increase in parallel from 1wPL to 5wPL; (6) GABA A ␣1 levels increase from 1wPL to 2wPL but do not change after this time point; and (7) GABA contents remain low from 1wPL to 5wPL. This is a comprehensive study showing for the first time that functional reorganization correlates in time with dendritic sprouting and with changes in the excitatory/inhibitory neurotransmission systems previously proposed to participate in cortical remodeling and suggests mechanisms by which plasticity of cortical representations may occur.Key words: plasticity; visual cortex; sprouting; maps; ischemia; injury; imaging techniques; cat; retinotopy; receptors; photochemical lesion; unmasking IntroductionCNS as well as PNS lesions lead to functional deficits, yet recovery of the lost functions may occur over time. It has been proposed that restoration of functions after focal somatosensory and motor cortical damage (Nudo et al., 1996a;Rouiller et al., 1998a;Coq and Xerri, 1999;Rijntjes and Weiller, 2002) may rely, to some degree, on the reorganization of cortical maps. Cortical reorganization has been observed to involve either zones surrounding the lesion area (Castro and Borrell, 1995;Nudo et al., 1996a;Rouiller et al., 1998a;Zepeda et al., 1999Zepeda et al., , 2003 or regions within the homologous contralateral cortex (Jones and Schallert, 1992;Jones et al., 1996;Nudo et al., 1996b;Dijkhuizen et al., 2003).Reorganization of the visual cortex after focal lesions has been studied less until recently despite its clinical relevance. We have previously shown that visual cortex maps reorganize to a certain extent with time after an ischemic lesion (Zepeda et al., 2003), while Eysel and Schweigart (1999) have reported that single cells in the surrounding area of the lesion exhibit enlarged receptive fields. However, neurorepair mechanisms associated with such visual reorganizat...

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Section: Methodsmentioning

confidence: 99%

Functional Reorganization of Visual Cortex Maps after Ischemic Lesions Is Accompanied by Changes in Expression of Cytoskeletal Proteins and NMDA and GABA_AReceptor Subunits

Zepeda

Sengpiel

Guagnelli³

et al. 2004

J. Neurosci.

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“…Amino acids in the cell extracts were quantified by high performance liquid chromatography (HPLC) analysis after derivatization with o-phthaldialdehyde essentially as described by Geddes and Wood (1984). HPLC analysis was performed by using a Varian solvent delivery system 9010, autosampler 9100, and computer system 4.02.…”

Section: Amino Acid Determinationmentioning

confidence: 99%

Synthesis of vesicular GABA from glutamine involves TCA cycle metabolism in neocortical neurons

Waagepetersen¹,

Sonnewald

Larsson³

et al. 1999

J. Neurosci. Res.

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In contrast to the classic concept of direct conversion of glutamine to gamma-aminobutyric acid (GABA; via glutamate), this process may involve alpha-ketoglutarate as an intermediary metabolite and tricarboxylic acid (TCA) cycle activity. To obtain information about a possible differential role of these pathways for the synthesis of cytosolic and vesicular GABA, cultured neocortical neurons were incubated in medium containing [U-(13)C]glucose (0.5 mM) and in some cases unlabeled glutamine (0.5 mM). Subsequently, the cells were "superfused" for investigation of the effect of depolarization by 55 mM K+. To make sure that depolarization by 55 mM K+ released only vesicular GABA, tiagabin, a nontransportable inhibitor of the plasma membrane GABA carriers, was included in the medium to prevent GABA release from the cytoplasmic pool by reversal of the carriers. The importance of the TCA cycle for conversion of the carbon skeleton of glutamine to GABA was evident from the effect of glutamine on the labeling pattern of GABA. Percentage of labeling by GABA released into the depolarizing medium was the same as that in the corresponding cell extracts and was unaffected by the presence of glutamine during incubation. Despite the existence of multiple forms of glutamate decarboxylase, compartmentation of glutamate pools, and functionally different compartments within neurons, there appears to be full equilibration between the vesicular and cytosolic pools of GABA. However, during depolarization, the newly synthesized pool of GABA from glutamine does not rapidly equilibrate with the vesicular pool.

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“…After 2 h, the medium was removed and lyophilized, and the cells were extracted with PCA as described previously (Sonnewald et al, 1991). Amino acids were measured in thePCA extracts by HPLC after derivatization with o-phthaldialdehyde (Geddes and Wood, 1984) using fluorometric detection. Metabolites in the medium were assayed enzymatically.…”

Section: Cell Cultures Experimental Conditions and Biochemical Measmentioning

confidence: 99%

Evaluation of the importance of transamination versus deamination in astrocytic metabolism of [U-13C] glutamate

Westergaard¹,

Drejer²,

Schousboe³

et al. 1996

Glia

106

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Changes in the Amino Acid Content of Nerve Endings (Synaptosomes) Induced by Drugs that Alter the Metabolism of Glutamate and γ‐Aminobutyric Acid

Cited by 128 publications

References 20 publications

Functional Reorganization of Visual Cortex Maps after Ischemic Lesions Is Accompanied by Changes in Expression of Cytoskeletal Proteins and NMDA and GABA_AReceptor Subunits

Functional Reorganization of Visual Cortex Maps after Ischemic Lesions Is Accompanied by Changes in Expression of Cytoskeletal Proteins and NMDA and GABA_AReceptor Subunits

Synthesis of vesicular GABA from glutamine involves TCA cycle metabolism in neocortical neurons

Evaluation of the importance of transamination versus deamination in astrocytic metabolism of [U-13C] glutamate

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Changes in the Amino Acid Content of Nerve Endings (Synaptosomes) Induced by Drugs that Alter the Metabolism of Glutamate and γ‐Aminobutyric Acid

Cited by 128 publications

References 20 publications

Functional Reorganization of Visual Cortex Maps after Ischemic Lesions Is Accompanied by Changes in Expression of Cytoskeletal Proteins and NMDA and GABAAReceptor Subunits

Functional Reorganization of Visual Cortex Maps after Ischemic Lesions Is Accompanied by Changes in Expression of Cytoskeletal Proteins and NMDA and GABAAReceptor Subunits

Synthesis of vesicular GABA from glutamine involves TCA cycle metabolism in neocortical neurons

Evaluation of the importance of transamination versus deamination in astrocytic metabolism of [U-13C] glutamate

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Product

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Functional Reorganization of Visual Cortex Maps after Ischemic Lesions Is Accompanied by Changes in Expression of Cytoskeletal Proteins and NMDA and GABA_AReceptor Subunits

Functional Reorganization of Visual Cortex Maps after Ischemic Lesions Is Accompanied by Changes in Expression of Cytoskeletal Proteins and NMDA and GABA_AReceptor Subunits