Different Dynamics of Aquaporin 4 and Glutamate Transporter‐1 Distribution in the Perineuronal and Perivascular Compartments during Ischemic Stroke

Mogoantă, L; Ciurea, Marius Eugen; Pirici, Ionica; Mărgăritescu, Claudiu; Simionescu, Cristiana; Ion, Daniela Adriana; Pirici, Daniel

doi:10.1111/bpa.12134

Cited by 37 publications

(32 citation statements)

References 53 publications

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“…The co-localization of AQP4 and EAAT2 was diminished in striatal astrocytes of equilibrative nucleoside transporter 1 (ENT1) null mice compared with wild-type littermates [59,60]. In addition, it was also observed co-localization between AQP4 and GFAP expression [59,60] in the striatum of ENT1 null mice [60].…”

Section: Eaat2-aqp4 Interactions In Astrocytes and Parkinson's Diseasementioning

confidence: 99%

“…In the mammalian brain and spinal cord, AQP4 is co-localized with glutamate transporters of EAAT1 and EAAT2, as well as with Kir 4.1 in the astrocyte plasma membrane, which suggests that AQP4 could modulate K + and glutamate homeostasis [56]. Functionally, AQP4 and EAAT2 exist in astrocytic membranes, and are physically linked in a macromolecular complex of several brain regions and spinal cord [10,23,[57][58][59][60]. The immunohistochemical analysis of non-pathologic human CNS tissue of both, cortical and the spinal cord, reveal that EAAT2 is normally co-localized with AQP4 in gray matter astrocytes [10].…”

Section: Eaat2-aqp4 Interactions In Astrocytes and Parkinson's Diseasementioning

confidence: 99%

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The Potential Role of Astrocytes in Parkinson’s Disease (PD)

Gebreyesus

Gebremichael

2020

Medical Sciences

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Astrocytes are multi-functional cells, now recognized as critical participants in many brain functions. They play a critical physiological role in the clearance of neurotransmitters, such as glutamate and gamma-aminobutyric acid (GABA), and in the regulation of K+ from the space of synaptic clefts. Astrocytes also express the excitatory amino acid transporters (EAATs) and aquaporin-4 (AQP4) water channel, which are involved in both physiological functions and neurodegenerative diseases (ND). Some of the ND are the Alzheimer’s (AD), Huntington’s (HD), Parkinson’s diseases (PD), Cerebral edema, amyotrophic lateral sclerosis (ALS), and epilepsy pathological conditions in specific regions of the CNS. Parkinson’s disease is the second most common age-related neurodegenerative disorder, characterized by degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNpc). These project to the striatum, forming an important pathway within the basal ganglia. Mostly, PD has no clear etiology, and the mechanism of dopaminergic (DA) neuron loss is not well illustrated. The results of various studies suggest that astrocytes are involved in the pathophysiology of PD. Evidence has shown that the down-regulation of EAAT-2/GLT-1 and AQP4 expression is associated with PD pathogenesis. However, controversial results were reported in different experimental studies about the expression and function of EAAT-2/GLT-1 and AQP4, as well as their colocalization in different brain regions, and their involvement in PD development. Therefore, under neurological disorders, Parkinson’s disease is related to the genetic and phenotypic change of astrocytes’ biology. In this review, the authors summarized recent their research findings, which revealed the involvement of EAAT-2/GLT-1 and AQP4 expression, the physical interaction between EAAT-2/GLT-1 and AQP4 in astrocyte function, and their potential role in the development of PD in SNpc and Subthalamic nucleus (STN) of the basal ganglia nuclei.

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Section: Eaat2-aqp4 Interactions In Astrocytes and Parkinson's Diseasementioning

confidence: 99%

Section: Eaat2-aqp4 Interactions In Astrocytes and Parkinson's Diseasementioning

confidence: 99%

The Potential Role of Astrocytes in Parkinson’s Disease (PD)

Gebreyesus

Gebremichael

2020

Medical Sciences

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“…Five types of glutamate transporter have been found in the mammalian CNS. The two types expressed predominantly in glial cells, glutamate transporter-1 (GLT-1) and glutamate and aspartate transporter (GLAST), maintain glutamate homeostasis under physiological and pathological conditions (Mogoanta et al, 2014). Several studies have shown that up-regulation of glutamate transporter reduces cerebral infarct volumes and astrocyte swelling (Verma et al, 2010; Benesova et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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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“…Overexpression of GLT-1/EAAT-2 in the ischemic cortex reduces the size of lesion and improves the behavioral recovery (Harvey et al, 2011). The modulation of GLT-1/EAAT-2 has been shown to exert neuroprotection in various models of ischemic injury and motor neuron degeneration (Mogoanta et al, 2014). An attempt to explore the neuroprotective potential in cerebral ischemia/reperfusion injury was also made by using ceftriaxone, a GLT-1/EAAT-2 modulator which provides overwhelming evidence that modulation of GLT-1/ EAAT-2 protein expression and activity confers neuroprotection in cerebral ischemia/reperfusion injury (Verma et al, 2010).…”

Section: Strokementioning

confidence: 99%