Glutamate-induced swelling of single astroglial cells in primary culture

Hanssoń, Elisabeth; Johansson, Björn; Westergren, Irena; Rönnbäck, Lars

doi:10.1016/0306-4522(94)90572-x

Cited by 45 publications

(30 citation statements)

References 31 publications

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“…In this study, we found that stimulation of cultured astrocytes with 1 mM glutamate increased cell swelling but had no effect on cell viability. Consistent with our results, many studies have demonstrated that swelling of cultured astrocytes occurs following glutamate treatment (Hansson et al, 1994; Yuan and Wang, 1996; Gunnarson et al, 2008). In contrast, Zhang et al (2014) reported that 1 mM glutamate induced neuronal cell death in culture (Zhang and Bhavnani, 2006), while Szydlowska et al (2006) found apoptotic alterations in the nuclear morphology of cultured astrocytes after 24-h incubation in 50–100 mM glutamate.…”

Section: Discussionsupporting

confidence: 93%

Aquaporin 4-Mediated Glutamate-Induced Astrocyte Swelling Is Partially Mediated through Metabotropic Glutamate Receptor 5 Activation

Shi

Zhang

Lü

et al. 2017

Front. Cell. Neurosci.

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Astrocytes are one of the most abundant cell types in the mammalian central nervous system (CNS), and astrocyte swelling is the primary event associated with brain edema. Glutamate, the principal excitatory amino acid neurotransmitter in the CNS, is released at high levels after brain injury including cerebral ischemia. This leads to astrocyte swelling, which we previously demonstrated is related to metabotropic glutamate receptor (mGluR) activation. Aquaporin 4 (AQP4), the predominant water channel in the brain, is expressed in astrocyte endfeet and plays an important role in brain edema following ischemia. Studies recently showed that mGluR5 is also expressed on astrocytes. Therefore, it is worth investigating whether AQP4 mediates the glutamate-induced swelling of astrocytes via mGluR5. In the present study, we found that 1 mM glutamate induced astrocyte swelling, quantified by the cell perimeter, but it had no effect on astrocyte viability measured by the cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays. Quantitative reverse transcription polymerase chain reaction analyses revealed that AQP4, among AQP1, 4, 5, 9 and 11, was the main molecular expressed in cultured astrocytes. Glutamate-induced cell swelling was accompanied by a concentration-dependent change in AQP4 expression. Furthermore, RNAi technology revealed that AQP4 gene silencing inhibited glutamate-induced astrocyte swelling. Moreover, we found that mGluR5 expression was greatest among the mGluRs in cultured astrocytes and was co-expressed with AQP4. Activation of mGluR5 in cultured astrocytes using (S)-3,5-dihydroxyphenylglycine (DHPG), an mGluR5 agonist, mimicked the effect of glutamate. This effect was abolished by co-incubation with the mGluR5 antagonist fenobam but was not influenced by DL-threo-β-benzyloxyaspartic acid (DL-TBOA), a glutamate transporter inhibitor. Finally, experiments in a rat model of transient middle cerebral artery occlusion (tMCAO) revealed that co-expression of mGluR5 and AQP4 was increased in astrocyte endfeet around capillaries in the penumbra, and this was accompanied by brain edema. Collectively, these results suggest that glutamate induces cell swelling and alters AQP4 expression in astrocytes via mGluR5 activation, which may provide a novel approach for the treatment of edema following brain injury.

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Section: Discussionsupporting

confidence: 93%

Aquaporin 4-Mediated Glutamate-Induced Astrocyte Swelling Is Partially Mediated through Metabotropic Glutamate Receptor 5 Activation

Shi

Zhang

Lü

et al. 2017

Front. Cell. Neurosci.

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“…Glutamate is the most common excitatory neurotransmitter in the mammalian CNS, with transporters located on astroglia responsible for maintaining the resting extracellular concentration of glutamate low to prevent it from reaching toxic levels (32,33). High (millimolar) concentrations of extracellular glutamate have been shown to induce cell swelling (25)(26)(27)(28). This suggests that the longest-lived component of rat optic nerve may result from intracellular water, axonal and/or glial.…”

Section: Compartment-component Relationshipmentioning

confidence: 96%

“…A second approach to determining the component-compartment relationship was then attempted. This was accomplished through the induction of cell swelling caused by the neurotransmitter glutamate, reported to result in neuronal and glial cell swelling in the CNS (25)(26)(27)(28). No reports have appeared on a corresponding swelling in the peripheral nervous system (PNS).…”

Section: Assignment Of T 2 Components To Water Compartmentsmentioning

confidence: 97%

Transverse relaxation in rat optic nerve

Bonilla¹,

Snyder²

2006

NMR in Biomedicine

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In vitro investigations were performed to study the proton T(2) relaxation spectrum of rat optic nerve. Studies in which the nerve was incubated in a D(2)O-based solution revealed that >98% of the spectrum originated from the water protons. The spectrum was found to consist of three components having relaxation times and sizes similar to those reported in the literature for peripheral nerve. Procedures were taken to confirm the existence of a third optic nerve component and that it was not an artifact of the long-lived water protons of the in vitro incubation solution. Evidence using paramagnetic agents in the incubation solution, which removed the two longest-lived nerve components from the spectrum, revealed the existence of a small fourth component (<10% of total) having a T(2) relaxation time similar to that of the intermediate-lived nerve component. Bathing the nerves in a 10 mM glutamate solution, glutamate known to result in cellular swelling in mammalian central nervous system (CNS), was found to increase the component size of the longest-lived nerve component, suggestive that this component may result from cellular water.

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“…Thus, application of glutamate, 1s ,3R-ACPD, or the selective group I11 mGluR agonist L-AP4, but not the iGluR agonists AMPA or kainate, resulted in a 5-12% increase in cell volume as measured by Fura-2 fluorescence at the isosbestic point where it is calcium insensitive. This response was blocked by the mGluR antagonist (S)-4-car-boxyphenylglycine and by pretreatment with pertussis toxin (Hansson, 1994;Hansson et al, 1994).…”

Section: Mglur Regulation Of Glial Swellingmentioning

confidence: 99%