Microdialysis of GABA and glutamate: Analysis, interpretation and comparison with microsensors

Zeyden, Miranda van der; Oldenziel, Weite Hendrik; Rea, Kieran; Cremers, Thomas; Westerink, Ben H.C.

doi:10.1016/j.pbb.2007.09.004

Cited by 138 publications

(97 citation statements)

References 120 publications

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“…Extracellular levels of glutamate, as sampled by microdialysis, are not easy to interpret because they are partially from nonvesicular sources and are affected by changes of glutamate release and uptake into glial cells (van der Zeyden et al, 2008). In the present study, glutamate levels did not strongly respond to behavioral activation (Fig.…”

Section: Downloaded Fromcontrasting

confidence: 52%

Neurotransmitters and Energy Metabolites in Amyloid-Bearing APP_SWE×PSEN1dE9 Mouse Brain

Hartmann¹,

Kiewert²,

Klein³

2009

J Pharmacol Exp Ther

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Alzheimer's disease is characterized by amyloid peptide formation and deposition, neurofibrillary tangles, synaptic loss and central cholinergic dysfunction, dysfunction of energy metabolism, and dementia; however, the interactions between these hallmarks remain poorly defined. We studied a well characterized mouse model of amyloid deposition, the doubly transgenic APP SWE ϫPSEN1dE9 mouse. At 10 to 14 months of age, these mice had high levels of amyloid peptides (6.6 g/g wet weight) and widespread amyloid plaques. Extracellular levels of acetylcholine (ACh) were determined by microdialysis in the hippocampus and were comparable with nontransgenic mice from the same colony. In the open field, both mouse strains responded with a 3-fold increase of hippocampal ACh release. Exploratory behavior of the transgenic mice appeared normal. Infusion of scopolamine evoked 5-to 6-fold increases of ACh levels in both mouse strains. High-affinity choline uptake and cholinesterase activities were identical in both mouse lines. Extracellular levels of glucose and glycerol were similar in control and transgenic mice, whereas lactate levels were slightly (p ϭ 0.06) and glutamate levels significantly (p ϭ 0.02) lower in transgenic mice. Exploration caused increases of glucose and lactate, whereas infusion of scopolamine (1 M) increased glucose but not lactate. Glutamate levels were increased by scopolamine, whereas glycerol remained constant under all the conditions. We conclude that amyloid peptide production and plaque deposition causes minor changes in cholinergic function and energy metabolites in transgenic mice in vivo. Amyloid peptide formation and/or deposition may not be sufficient for long-term cholinergic or metabolic dysfunction.Alzheimer's disease (AD) is the most frequent type of dementia in humans and is characterized by cognitive dysfunction and early memory loss (Blennow et al., 2006;Burns and Iliffe, 2009). AD brains display amyloid plaques and neurofibrillary tangles, as well as neuronal degeneration and generalized atrophy. Cholinergic fibers originating in the basal forebrain and innervating hippocampus and cortex seem to degenerate relatively early in the disease, although the clinical evidence is somewhat controversial (Mesulam, 2006;Schliebs and Arendt, 2006). In later stages of the disease, cholinergic dysfunction correlates well with dementia, and current therapies of AD use inhibitors of acetylcholinesterase (AChE) to enhance cholinergic transmission in the brain. Although treatment of AD with AChE inhibitors as a monotherapy has only limited effects, successful treatment of dementia will probably not be possible without correcting the cholinergic deficit. Thus, the understanding of the cholinergic dysfunction and its development remains highly relevant for drug treatment of AD.In clinical studies, AD can be distinguished in early onset disease (familial AD) and late-onset, sporadic disease (Blennow et al., 2006;Burns and Iliffe, 2009). The rare familial AD cases have mutations in genes coding for...

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Section: Downloaded Fromcontrasting

confidence: 52%

Neurotransmitters and Energy Metabolites in Amyloid-Bearing APP_SWE×PSEN1dE9 Mouse Brain

Hartmann¹,

Kiewert²,

Klein³

2009

J Pharmacol Exp Ther

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“…We found that the basal extracellular glutamate level was significantly reduced in p55 Ϫ/Ϫ mice as compared to wild-type controls while it did not change in p75 Ϫ/Ϫ mice. We speculate that the decrease in basal extracellular glutamate levels in p55 Ϫ/Ϫ mice is due to a reduction in astrocytic glutamate release for the following reasons: (1) the basal extracellular glutamate level measured by microdialysis likely reflects glutamate release from astrocytes since it is insensitive to tetrodotoxin (TTX) and has a low dependence on Ca 2ϩ (Del Arco et al, 2003;van der Zeyden et al, 2008); (2) TNFalpha induces the astrocytic release of glutamate acting on p55 receptors (Bezzi et al, 2001), thus supporting our finding of a reduced basal glutamate release in the absence of p55 receptors.…”

Section: Discussionmentioning

confidence: 99%

Molecular and functional interactions between tumor necrosis factor-alpha receptors and the glutamatergic system in the mouse hippocampus: Implications for seizure susceptibility

et al. 2009

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Abstract-Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine acting on two distinct receptor subtypes, namely p55 and p75 receptors. TNF-alpha p55 and p75 receptor knockout mice were previously shown to display a decreased or enhanced susceptibility to seizures, respectively, suggesting intrinsic modifications in neuronal excitability. We investigated whether alterations in glutamate system function occur in these naive knockout mice with perturbed cytokine signaling that could explain their different propensity to develop seizures. Using Western blot analysis of hippocampal homogenates, we found that p55 ؊/؊ mice have decreased levels of membrane GluR3 and NR1 glutamate receptor subunits while GluR1, GluR2, GluR6/7 and NR2A/B were unchanged as compared to wild-type mice. In p75 ؊/؊ mice, GluR2, GluR3, GluR6/7 and NR2A/B glutamate receptor subunits were increased in the hippocampus while GluR1 and NR1 did not change. Extracellular single-cell recordings of the electrical activity of hippocampal neurons were carried out in anesthetized mice by standard electrophysiological techniques. Microiontophoretic application of glutamate increased the basal firing rate of hippocampal neurons in p75 ؊/؊ mice versus wild-type mice, and this effect was blocked by 2-amino-5-phosphopentanoic acid and 6-nitro-7-sulfamoyl-benzo(f)quinoxaline-2,3-dione denoting the involvement of N-methyl-D-aspartic acid and AMPA receptors. In p55؊/؊ mice, hippocampal neurons responses to glutamate were similar to wild-type mice. Spontaneous glutamate release measured by in vivo hippocampal microdialysis was significantly decreased only in p55 ؊/؊ mice. No changes were observed in KCl-induced glutamate release in both receptor knockout mice strains versus wild-type mice. These findings highlight specific molecular and functional interactions between p55 and p75 receptor-mediated signaling and the glutamate system. These interactions may be relevant for controlling neuronal excitability in physiological and pathological conditions.

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“…There was no significant effect of VGLUT1-targeting shRNA on basal levels of extracellular glutamate (control, 0.395 ± 0.179 mM; VGLUT1, 0.499±0.257 mM; P40.05), but the increase in glutamate efflux observed on inclusion of the glutamate reuptake inhibitor TBOA in the perfusate (time: F (15, 209) Although the majority of GABA efflux measured by microdialysis fulfills the criteria for exocytotic release, basal glutamate detected with this technique is not calcium dependent or sensitive to sodium channel blockade by tetrodotoxin (van der Zeyden et al, 2008), suggesting it is largely of extrasynaptic origin. In contrast, recently developed glutamate microsensors (enzyme-coated microelectrode arrays coupled with electrochemical detection) provide greater spatial and temporal resolution than microdialysis, and evidence shows that part of the basal glutamate efflux detected by this method is tetrodotoxin sensitive (Day et al, 2006).…”

Section: Intrahippocampal Administration Of Vglut1-targeting Shrna Sementioning

confidence: 92%

Lentiviral Delivery of a Vesicular Glutamate Transporter 1 (VGLUT1)-Targeting Short Hairpin RNA Vector Into the Mouse Hippocampus Impairs Cognition

King

Kurian

Qin

et al. 2013

Neuropsychopharmacol

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Glutamate is the principle excitatory neurotransmitter in the mammalian brain, and dysregulation of glutamatergic neurotransmission is implicated in the pathophysiology of several psychiatric and neurological diseases. This study utilized novel lentiviral short hairpin RNA (shRNA) vectors to target expression of the vesicular glutamate transporter 1 (VGLUT1) following injection into the dorsal hippocampus of adult mice, as partial reductions in VGLUT1 expression should attenuate glutamatergic signaling and similar reductions have been reported in schizophrenia. The VGLUT1-targeting vector attenuated tonic glutamate release in the dorsal hippocampus without affecting GABA, and selectively impaired novel object discrimination (NOD) and retention (but not acquisition) in the Morris water maze, without influencing contextual fear-motivated learning or causing any adverse locomotor or central immune effects. This pattern of cognitive impairment is consistent with the accumulating evidence for functional differentiation along the dorsoventral axis of the hippocampus, and supports the involvement of dorsal hippocampal glutamatergic neurotransmission in both spatial and nonspatial memory. Future use of this nonpharmacological VGLUT1 knockdown mouse model could improve our understanding of glutamatergic neurobiology and aid assessment of novel therapies for cognitive deficits such as those seen in schizophrenia.

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Microdialysis of GABA and glutamate: Analysis, interpretation and comparison with microsensors

Cited by 138 publications

References 120 publications

Neurotransmitters and Energy Metabolites in Amyloid-Bearing APP_SWE×PSEN1dE9 Mouse Brain

Neurotransmitters and Energy Metabolites in Amyloid-Bearing APP_SWE×PSEN1dE9 Mouse Brain

Molecular and functional interactions between tumor necrosis factor-alpha receptors and the glutamatergic system in the mouse hippocampus: Implications for seizure susceptibility

Lentiviral Delivery of a Vesicular Glutamate Transporter 1 (VGLUT1)-Targeting Short Hairpin RNA Vector Into the Mouse Hippocampus Impairs Cognition

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Microdialysis of GABA and glutamate: Analysis, interpretation and comparison with microsensors

Cited by 138 publications

References 120 publications

Neurotransmitters and Energy Metabolites in Amyloid-Bearing APPSWE×PSEN1dE9 Mouse Brain

Neurotransmitters and Energy Metabolites in Amyloid-Bearing APPSWE×PSEN1dE9 Mouse Brain

Molecular and functional interactions between tumor necrosis factor-alpha receptors and the glutamatergic system in the mouse hippocampus: Implications for seizure susceptibility

Lentiviral Delivery of a Vesicular Glutamate Transporter 1 (VGLUT1)-Targeting Short Hairpin RNA Vector Into the Mouse Hippocampus Impairs Cognition

Contact Info

Product

Resources

About

Neurotransmitters and Energy Metabolites in Amyloid-Bearing APP_SWE×PSEN1dE9 Mouse Brain

Neurotransmitters and Energy Metabolites in Amyloid-Bearing APP_SWE×PSEN1dE9 Mouse Brain