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J Vitorica

Publications and source records attributed to J Vitorica.

At least 37 records · Page 2Linked to original sources
PubMed1993

Absence of modifications of the pharmacological properties of the GABAA receptor complex during aging, as assessed in 3- and 24-month-old rat cerebral cortex.

We have investigated the possible modifications of the pharmacological properties of Type I and Type II benzodiazepine binding sites of the gamma-aminobutyric acidA (GABAA) receptor complex in cortical membranes from 3- and 24-month-old Wistar or Fischer rats. No major changes were found in the binding parameters of [3H]zolpidem (a Type I-specific ligand) or [3H]flunitrazepam (a non-selective benzodiazepine). Neither the Kd values nor the Bmax for either ligand were modified during aging in cortical membranes from Wistar or Fischer rats. Consequently, the proportion of Type I binding sites was also unmodified in aged cortical membranes. The absence of modifications of Type I and Type II binding sites was also confirmed by Cl 218,872 displacement of [3H]flunitrazepam binding in aged cortical membranes from Wistar rats. Furthermore, the [3H]muscimol binding and the allosteric interactions between Type I or total benzodiazepine binding sites and GABA binding sites also remained unaltered with aging in cortical membranes from Wistar rats. Moreover, the pattern and proportion of the [3H]flunitrazepam photoaffinity labeled peptides were also unmodified by aging. These results demonstrate the absence of modifications in Type I or total benzodiazepine binding sites of the GABAA receptor complex from adult and aged cortical membranes in Fischer or Wistar rats.

Affinity Labels↗
PubMed1993

Comparative autoradiographic distribution of central omega (benzodiazepine) modulatory site subtypes with high, intermediate and low affinity for zolpidem and alpidem.

Pharmacological characterization of [3H]benzodiazepine binding to membrane preparations of adult rat hippocampus and neonatal rat brain have demonstrated, in addition to the omega 1 and omega 2 populations of central omega benzodiazepine binding sites associated with GABAA receptors, the existence of binding sites with microM affinity for the imidazopyridines zolpidem and alpidem. In the present study we have investigated their comparative autoradiographic distribution using [3H]flumazenil as a ligand. In the neonatal rat CNS, the imidazopyridine derivatives zolpidem and alpidem were found to discriminate two [3H]flumazenil binding site populations with an IC50 value ratio of more than 200-fold. In the different regions investigated (spinal cord, striatum, neocortex and inferior colliculus) the low affinity component had IC50 values of 20-40 microM (zolpidem) and 5-15 microM (alpidem) and accounted for ca. 50% of the total binding site population. In the adult rat, these imidazopyridine derivatives displayed a greater displacing potency in the cerebellum (IC50 = 6 and 36 nM, respectively) than in the hippocampus (IC50 = 37 and 403 nM, respectively). In the cerebellum, [3H]flumazenil binding was fully displaced by 1 microM of either compound and Hill coefficients of displacement curves were close to unity. In the hippocampus, 25% of [3H]flumazenil binding were resistant to 3 microM zolpidem or 1 microM alpidem, but were displaced by 100 microM of either compound. CL 218,872 also displayed a greater displacing potency in the cerebellum (IC50 = 83 nM) than in the hippocampus (IC50 = 711 nM) but [3H]flumazenil binding in the hippocampus was fully displaced by 10 microM of this compound. In adult rat hippocampus, zolpidem and alpidem were found to discriminate between three central omega site subtypes which display high (IC50 = 31 and 6.1 nM, for these imidazopyridine derivatives. In contrast, CL 218,872 discriminated between omega 1 and omega 2 sites but not between two omega 2 receptor subpopulations. omega 1 sites were mainly localized in layer IV of the sensorimotor cortex, cerebellum, substantia nigra, olfactory bulb and inferior colliculus. omega 2I sites were present in the cortical mantle (with higher levels in the cingulate and olfactory than in the sensorimotor cortex) and in subcortical (hippocampus, hypothalamus and nucleus accumbens) limbic structures. In the hippocampus, hypothalamus, spinal cord and nucleus accumbens, omega 2L sites accounted for more than 25% of the specific [3H]flumazenil binding; the density of these sites was minor in the cortex and in most pyramidal and extrapyramidal system structures.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Regional differences in the enhancement by GABA of [3H]zolpidem binding to omega 1 sites in rat brain membranes and sections.

The potential heterogeneity in the allosteric coupling between GABA and omega 1 binding sites within the native GABAA receptor complex has been evaluated in the rat by measuring the enhancement by GABA of [3H]zolpidem binding to omega 1 site in membranes from three rat brain structures (neocortex, cerebellum and hippocampus) and brain sections. The maximal stimulatory effect of GABA was significantly higher (265 +/- 47%) in cortical membranes than in cerebellar (165 +/- 48%) or in hippocampal (118 +/- 17%) membranes. These differences are not due either to the presence of different amounts of residual GABA in the membrane preparations or to the labeling, in presence of GABA, of binding sites other than omega 1 since: (1) the pharmacological properties of the [3H]zolpidem binding sites were similar in the three regions; (2) the degree of allosteric enhancement was unrelated to the relative proportion of omega 1 sites in each structure; and (3) GABA did not increase the Bmax for [3H]zolpidem. Regional differences in the effect of 100 microM GABA on [3H]zolpidem binding were also observed by quantitative autoradiography. Regions where the strongest (3-4-fold) effects of GABA in [3H]zolpidem binding were observed included the substantia nigra, lateral geniculate body, olfactory tubercule and red nucleus. A large increase in [3H]zolpidem binding was also demonstrated in the cingulate and frontoparietal cortices with higher effects in deep (4.2-fold) rather than in superficial layers (3.3-fold). Heterogeneous subregional increases in [3H]zolpidem binding in the presence of GABA were quantified within the cerebellum, hippocampus and superior colliculus.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1992

Heterogeneity in the allosteric interaction between the gamma-aminobutyric acid (GABA) binding site and three different benzodiazepine binding sites of the GABAA/benzodiazepine receptor complex in the rat nervous system.

In the present communication we have investigated the allosteric coupling between the gamma-aminobutyric acidA (GABAA) receptor and the pharmacologically different benzodiazepine (BZD) receptor subtypes in membranes from various rat nervous system regions. Two types of BZD receptors (type I and type II) have been classically defined using CL 218.872. However, using zolpidem, three different BZD receptors have been identified by binding displacement experiments in membranes. These BZD receptor subtypes displayed high, low, and very low affinity for zolpidem. The distribution of the high- and low-affinity binding sites for zolpidem was similar to that of type I and type II subtypes in cerebellum, prefrontal cortex, and adult cerebral cortex. On the other hand, the very-low-affinity binding site was localized in relative high proportion in spinal cord, hippocampus, and newborn cerebral cortex and, to a minor extent, in superior colliculus. The allosteric coupling between the GABAA receptor and the BZD receptor subtypes was different. The high- and low-affinity binding sites for zolpidem seemed to have a similar high degree of coupling, except in spinal cord. On the other hand, the very-low-affinity binding site for zolpidem displayed a low degree of coupling with the GABAA receptor. These results seem to indicate that the different efficacy of GABA in enhancing the [3H]flunitrazepam binding could be due to the different BZD receptor subtypes present in the GABAA/BZD receptor complex and, moreover, led us to speculate that the low GABA efficacy found in membranes from spinal cord, hippocampus, and newborn cerebral cortex might be due to the presence in relatively high proportion of the very-low-affinity binding site for zolpidem.

Allosteric Site↗
PubMed1991

Purification of the gamma-aminobutyric acidA/benzodiazepine receptor complex by immunoaffinity chromatography.

The bovine gamma-aminobutyric acidA/benzodiazepine receptor complex has been purified by a novel immunoaffinity chromatography method on immobilized monoclonal antibody 62-3G1. Immunopurification of the complex was achieved in a single step with an improved yield over affinity chromatography on the benzodiazepine Ro 7-1986/1. High-resolution sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the immunoaffinity-purified receptor revealed three major peptide bands of 51,000, 55,000, and 57,000 Mr which were also present in the Ro 7-1986/1 affinity-purified receptor. Peptide mapping, immunoblotting with subunit specific antibodies, and photoaffinity labeling with [3H]flunitrazepam and [3H]muscimol have been used for the identification of receptor subunits, including several which comigrated in a single band in SDS-PAGE.

Affinity Labels↗
PubMed1991

Pharmacologic characterization of GABAA/benzodiazepine receptor in rat hippocampus during aging.

We have characterized the pharmacologic properties of the gamma-aminobutyric acid (GABAA)/benzodiazepine receptor complex in hippocampal membranes from 3-month- and 24-month-old Wistar rats. No major changes were found in [3H]flunitrazepam or [3H]muscimol binding parameters. Neither the dissociation constant(s) nor the Bmax for either ligand seemed to be modified during aging in hippocampus. Furthermore, the allosteric interaction between the barbiturates binding site and the GABA binding site, determined by pentobarbital stimulation of [3H] muscimol binding, remained unaltered. However, there was a significant increase with aging in the efficacy of the GABA-enhancement of [3H]flunitrazepam binding. On the other hand, we have also detected a significant increase in the proportion of type I benzodiazepine receptor in 24-month-old hippocampal membranes. We propose that the age-related increase in the efficacy of GABA-enhancement of [3H]flunitrazepam binding could be correlated with the increase in the proportion of type I benzodiazepine receptor. Based on these results it is tempting to speculate that the age-dependent modifications on the GABAA/benzodiazepine receptor might reflect an age-dependent neuronal degeneration of the hippocampus or the hippocampal formation.

Aging↗
PubMed1990

The GABAA/benzodiazepine receptor complex in rat brain neuronal cultures. Characterization by immunoprecipitation.

The expression of the GABAA/benzodiazepine receptor (GABAR/BZDR) complex in primary neuronal cultures from rat brain embryos has been investigated. The GABAR/BZDR complex was photoaffinity labeled with [3H]flunitrazepam [3H]FNZ and immunoprecipitated with subunit specific antibodies. These were the mAb 62-3G1 which is specific for the 57-kDa GABA binding subunit, and the rabbit antiserum A which recognizes the 51-kDa [3H]FNZ binding subunit. The results indicate that the cultured neurons express 5 different peptides of 51, 53, 54, 57 and 59 kDa that can be photoaffinity labeled with [3H]FNZ and that all of them are physically coupled to the GABAA receptor. Most of the [3H]FNZ photolabeled peptides have similar mobilities to those found in the brain of the newborn rat. Nevertheless, some of the quantitative changes in the photolabeled peptides observed during the normal development of the rat brain were not observed or occurred at much slower pace in the cultured neurons.

Affinity Labels↗
PubMed1990

Characterization with antibodies of the gamma-aminobutyric acidA/benzodiazepine receptor complex during development of the rat brain.

The postnatal development of the gamma-aminobutyric acidA/benzodiazepine receptor (GABAR/BZDR) complex of the rat brain has been investigated using the monoclonal antibody 62-3G1 and the polyclonal rabbit antiserum A, specific for the 57,000 and 51,000 Mr receptor subunits, respectively. Both GABAR and BZDR binding activities co-precipitated during all postnatal ages. Adult rats showed a main 51,000 Mr[3H]flunitrazepam photoaffinity-labeled peptide, whereas newborn rats showed several photolabeled peptides of higher Mr. All the photolabeled peptides could be immunoprecipitated with each antibody regardless of the age of the rats. These results suggest that the physical coupling between the GABAR and the BZDR is already present in newborn animals and it is maintained afterwards during development. Glycosidase and peptidase treatments of the immunoprecipitated GABAR/BZDR complex indicated that all the [3H]flunitrazepam-photolabeled subunits are different peptides, although they seem to conserve a high degree of homology. In addition to the age-dependent heterogeneity, the results also suggest that for each age, there is heterogeneity in the subunit composition of the GABAR/BZDR complex.

Acetylglucosaminidase↗
PubMed1990

Rapid postnatal developmental changes in the passive proton permeability of the inner membrane in rat liver mitochondria.

Titration of mitochondrial respiration against the membrane potential with the inhibitor malonate has been carried out during the perinatal period in isolated rat liver mitochondria. Neonatal and adult mitochondria exhibited the characteristic "nonohmic" behavior for the proton conductance (CmH+). In contrast, fetal mitochondria exhibited an "anomalous" "ohmic" behavior for CmH+. The calculated passive proton permeability of the membrane undergoes a profound reduction during the first postnatal hour. The results reported demonstrate that the hypothesis [Pollak, J.K. & Sutton, R. (1980) Trends Biochem. Sci. 5, 23-27] of the existence of a "leaky" mitochondria in the fetal rat liver, and of its sudden neonatal change towards a state of higher energy conservation of the proton electrochemical gradient, is correct.

Animals↗
PubMed1989

Immunocytochemical localization of GABAA receptors in goldfish and chicken retinas.

A monoclonal antibody (mAb 62-3G1) to the GABAA receptor/benzodiazepine receptor/Cl- channel complex from bovine brain was used with light and electron microscopy in goldfish retina and light microscopy in chicken retina to localize GABAA receptor immunoreactivity (GABAr-IR). GABAr-IR was found in the outer plexiform layer (OPL) in both species, in three broad bands in the inner plexiform layer (IPL) of goldfish, and in seven major bands of the chicken IPL. A small percentage of amacrine cell bodies (composing at least three types) were stained in chicken. In goldfish OPL, GABAr-IR was localized intracellularly and along the plasma membrane of cone pedicles, whereas rod spherules were lightly stained, but always only intracellularly. In chicken, all three sublayers of the OPL were GABAr-IR. The presence of GABAr-IR on photoreceptor terminals is consistent with data indicating feedback from GABAergic horizontal cells to cones. In the goldfish IPL, GABAr-IR was localized to postsynaptic sites of amacrine cell synapses; intracellular staining of processes in the IPL also was observed in presumed "GABAergic" targets. A comparison of GABAr-IR with the distributions of 3H-muscimol uptake/binding, glutamate decarboxylase-IR, GABA-IR, and 3H-GABA uptake in the IPL showed either a reasonable correspondence or mismatch, depending on the marker, species, and lamina within the IPL. The distribution of GABAr-IR in the retina corresponded better with the 3H-muscimol than with 3H-benzodiazepine binding patterns yet overall was in excellent agreement with many other physiological and anatomical indicators of GABAergic function. We suggest that intracellular GABAr-IR represents the biosynthetic and/or degradative pathway of the receptor and we conclude that mAb 62-3G1 is a valid marker of GABAA receptors in these retinas and will serve as a useful probe with which to address the issue of mismatches between the localization of GABAA receptors and indicators of presynaptic GABAergic terminals.

Animals↗
PubMed1989

Immunohistochemical localization of GABAA receptors in the retina of the new world primate Saimiri sciureus.

A large population of amacrine cells in the retina are thought to use GABA as an inhibitory neurotransmitter in their synaptic interactions within the inner plexiform layer. However, little is known about their synaptic targets; the neurons that express the receptors for GABA have not been clearly identified. Recently, the GABAA receptor has been isolated and antibodies have been raised against it. These antibodies have proven useful for the immunocytochemical localization of the receptor, and two brief reports describing the distribution of GABAA receptor immunoreactivity in the retina have appeared (Richards et al., 1987; Mariani et al., 1987). We used a monoclonal antibody (62-3G1) against the GABAA receptor to study the retina of the New World primate Saimiri sciureus. Labeled somata were found in the inner nuclear layer (INL) and ganglion cell layer (GCL). The staining was confined to what appeared to be the cell's plasmalemma and small cytoplasmic granules. Most of the labeled neurons in the INL had small somata (5-7 microns in diameter) located at the vitreal edge of the layer. They arborized in two laminae (approximately 2 and 4) of inner plexiform layer (IPL). Ventral to the optic disc (2.5 mm) they comprised 29% of the cells present. A few of the labeled neurons appeared to be interplexiform cells or flat bipolar cells, with labeled processes that extended into both the IPL and the inner half of the outer plexiform layer. In the GCL, the labeled somata were among the largest present (13-20 microns in diameter), and 2.5 mm ventral to the optic disc they made up 15% of the cells present. Experiments in which immunoreactive somata were retrogradely labeled following the injection of fluorescent tracers into the optic tract provided a conclusive demonstration that some of the immunoreactive somata were ganglion cells. The antibody often labeled their axons in the optic fiber layer. This suggests that the GABAA receptors are transported anterogradely to the retinal terminal fields. The dendrites of the immunoreactive ganglion cells extended into the 2 laminae of labeled processes in the IPL, and their primary dendritic arbors were, at any given eccentricity, quite similar in appearance. This homogeneity suggests that they comprise a particular subset of the ganglion cells. Sections simultaneously labeled with the monoclonal antibody against the GABAA receptor and antisera against either L-glutamic acid decarboxylase (GAD) or GABA revealed that the GAD/GABA was distributed much more widely in the IPL than the GABAA receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Localization of the GABAA receptor in the rat brain with a monoclonal antibody to the 57,000 Mr peptide of the GABAA receptor/benzodiazepine receptor/Cl- channel complex.

The mAb 62-3G1 to the GABAA receptor/benzodiazepine receptor/Cl- channel complex was used with light-microscopy immunocytochemistry for studying the localization of the GABAA receptors (GABAR) in the rat brain. The results have shown a receptor distribution identical to the one obtained by others using 3H-muscimol binding in combination with autoradiographic techniques. The external plexiform layer of the olfactory bulb, cerebral cortex, granule cell layer of the cerebellum, hippocampus, dentate gyrus, substantia nigra, dorsolateral and medium geniculate nuclei, and the lateral posterior thalamic nucleus, among other areas, were rich in GABAA receptor immunoreactivity. In the cerebellum the granule cell layer had more immunoreactivity than did the molecular layer. In the hippocampus the receptor was most abundant in the stratum oriens and in the molecular layer of the dentate gyrus. The immunocytochemical techniques have also allowed us to study the distribution of the GABAA receptor with high-resolution light microscopy. These studies have shown that the GABAA receptors are localized in neuronal membranes and concentrated in structures rich in GABAergic synapses, such as the cerebellar and olfactory glomeruli and the external plexiform layer of the olfactory bulb, the deep cerebellar nuclei, and the substantia nigra. The mAb 62-3G1 was generated by immunizing mice with the affinity-purified GABAA receptor/benzodiazepine receptor (BZDR) complex. This mAb bound to the 57,000 Mr peptide but not to the benzodiazepine binding 51,000 Mr peptide. The distribution of the GABAR immunoreactivity in the rat brain colocalized better with 3H-muscimol than with 3H-benzodiazepine binding. Therefore, it is suggested that (1) the 57,000 Mr peptide that is recognized by the mAb 62-3G1 is the muscimol (GABAA receptor agonist) binding subunit of the receptor complex, (2) there is an important population of brain GABAA receptors that is not functionally coupled to the benzodiazepine receptors, and (3) both the BZDR-coupled and uncoupled forms of the GABAA receptor are immunologically similar, if not identical.

Animals↗
PubMed1988

Monoclonal antibodies and conventional antisera to the GABAA receptor/benzodiazepine receptor/Cl- channel complex.

Monoclonal antibodies (mAbs) and conventional antisera were raised to the affinity-purified GABAA receptor/benzodiazepine receptor/Cl- channel complex. The antibodies immunoprecipitated the affinity-purified complex in Triton X-100 and also reacted with the complex in a solid-phase radioimmunoassay. Immunoblots indicated that the mAb 62-3G1 reacted with the 57,000 Mr peptide subunit of the affinity-purified complex, while the antisera mainly reacted with the 51,000 Mr peptide subunit. The mAbs and the antisera also immunoprecipitated the GABAA receptor/benzodiazepine receptor/Cl- channel complex after being solubilized from cerebral cortex membranes by the zwitterionic detergent CHAPS. The immunoprecipitated complex bound 3H-muscimol, 3H-flunitrazepam (FNZ) and 35S-t-butylbicyclophosphorothionate (TBPS). The 3H-FNZ binding was stimulated by GABA, indicating that the functional interactions among the immunoprecipitated components of the complex were preserved. The mAb 62-3G1 also recognized the 57,000 Mr peptide in immunoblots with crude brain membranes. Immunocytochemistry experiments showed that the binding of both the mAb 62-3G1 and 3H-muscimol colocalized throughout the brain. The results suggest that (1) the 57,000 Mr peptide is the muscimol (GABAA receptor agonist) binding peptide of the complex, and (2) in the cerebral cortex, most of the GABAA receptors (GABARs), benzodiazepine receptors (BDZRs), and Cl- channels are physically coupled to one another.

Animals↗
PubMed1986

Involvement of mitochondria in the age-dependent decrease in calcium uptake of rat brain synaptosomes.

Calcium uptake in rat brain synaptosomes decreases during ageing. The possible involvement of mitochondria in altered calcium homeostasis has been investigated. Mitochondria isolated from old rat brain showed decreased calcium uptake rates. Since neither the mitochondrial membrane potential nor the delta pCa decreases with age, it was concluded that variations in the driving force for calcium uptake were not the cause for impaired calcium transport in mitochondria from aged rat brain. The steady state calcium distribution in isolated aged rat brain mitochondria was achieved at higher extramitochondrial calcium concentrations than that of adults. Studying the effects of the selective release of calcium from the mitochondrial pool by the addition of an uncoupler to 45Ca loaded synaptosomes incubated in high-potassium media, it was found that the intrasynaptic mitochondrial pool and the intra/extramitochondrial 45Ca distribution also decreased considerably in 24-month-old rats. Steady state fluorescence anisotropy (rs) of diphenylhexatriene-labelled mitoplasts from 'free' brain mitochondria increased with ageing. However, since no changes in rs from synaptosomal mitochondria were found in 24-month-old rats, it is suggested that alterations in lipid dynamics are not involved in the impaired calcium uptake observed in brain mitochondria from aged rats. The implications of these findings in the calcium homeostasis of brain endings are discussed.

Aging↗
PubMed1985

The role of ADP in the modulation of the calcium-efflux pathway in rat brain mitochondria.

The role of ADP in the regulation of Ca2+ efflux in rat brain mitochondria was investigated. ADP was shown to inhibit Ruthenium-Red-insensitive H+- and Na+-dependent Ca2+-efflux rates if Pi was present, but had no effect in the absence of Pi. The primary effect of ADP is an inhibition of Pi efflux, and therefore it allows the formation of a matrix Ca2+-Pi complex at concentrations above 0.2 mM-Pi and 25 nmol of Ca2+/mg of protein, which maintains a constant free matrix Ca2+ concentration. ADP inhibition of Pi and Ca2+ efflux is nucleotide-specific, since in the presence of oligomycin and an inhibitor of adenylate kinase ATP does not substitute for ADP, is dependent on the amount of ADP present, and requires ADP concentrations in excess of the concentrations of translocase binding sites. Brain mitochondria incubated with 0.2 mM-Pi and ADP showed Ca2+-efflux rates dependent on Ca2+ loads at Ca2+ concentrations below those required for the formation of a Pi-Ca2+ complex, and behaved as perfect cytosolic buffers exclusively at high Ca2+ loads. The possible role of brain mitochondrial Ca2+ in the regulation of the tricarboxylic acid-cycle enzymes and in buffering cytosolic Ca2+ is discussed.

Adenosine Diphosphate↗
PubMed1985

The pentose phosphate cycle is regulated by NADPH/NADP ratio in rat liver.

The changes in the activity of the pentose phosphate cycle produced by the activation or inhibition of different NADPH-consuming pathways have been studied. The inhibition of fatty acid synthesis by kynurenate produced to the same extent, inhibition of the pentose phosphate cycle activity and an increase (about twofold) in the NADPH/NADP ratio. The addition of ter-butyl-hydroperoxide or paraquat, which is metabolized via NADPH-consuming pathways, produced the activation of the pentose phosphate cycle and a decrease in the NADPH/NADP ratio (about threefold). The plot of the NADPH/NADP ratio versus the pentose phosphate cycle activity gave a straight line with a regression index of 0.999. The regulation of the pentose phosphate cycle mainly by the intracellular NADPH/NADP ratio is discussed.

Animals↗
PubMed1985

Impairment of glutamate uptake and absence of alterations in the energy-transducing ability of old rat brain mitochondria.

The proton electrochemical gradient has been measured in old brain mitochondria isolated from 2- or 24-month-old rats with the use of different respiratory substrates. With succinate as substrate, neither the respiratory rate, membrane potential or delta pH varied with age, indicating that the dielectric strength of the mitochondrial membrane was unaltered in old animals. The ohmic behavior of the membrane was tested in experiments in which the respiratory rate was partially inhibited by malonate, and was found to be unchanged with age. When glutamate plus malate were used as substrates, the respiratory rate was substantially reduced, and a drastic decrease in glutamate uptake was observed in old rat brain mitochondria.

Aging↗