Region-specific expression of vesicular glutamate and GABA transporters under various ischaemic conditions in mouse forebrain and retina

Michalski, Dominik; Härtig, Wolfgang; Krügel, Katja; Edwards, Robert H.; Böddener, M.; Böhme, L; Pannicke, Thomas; Reichenbach, Andreas; Grosche, Antje

doi:10.1016/j.neuroscience.2012.11.046

Cited by 30 publications

(24 citation statements)

References 73 publications

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“…Importantly, the synaptic vesicle associated protein synaptophysin was not affected by transient MCAO, showing that the cleavage of VGAT is a specific event . In contrast with the results obtained in experiments using transient brain ischemia, 24 h of permanent MCAO in mice, which induced a downregulation of VGLUT2 and VGLUT3 in the neocortex, did not alter VGAT expression (Michalski et al, 2013). Why VGAT is preserved after permanent MCAO, in contrast with the effect after transient ischemia, remains to be determined.…”

Section: Calpain-mediated Cleavage Of Vesicular Gaba Transportercontrasting

confidence: 79%

“…More recently, an immunohistochemical study has shown that 24 h permanent MCAO in mice induced a downregulation of VGLUT2 and VGLUT3 in the neocortex but did not change VGLUT1 expression (Michalski et al, 2013). However, none of these studies addressed the molecular mechanisms involved in the alterations in VGLUT protein levels in the ischemic brain.…”

Section: Effects Of Calpain Activity At Glutamatergic Presynaptic Sitmentioning

confidence: 99%

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Calpains and neuronal damage in the ischemic brain: The swiss knife in synaptic injury

Curcio

Salazar

Mele

et al. 2016

Progress in Neurobiology

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Section: Calpain-mediated Cleavage Of Vesicular Gaba Transportercontrasting

confidence: 79%

Section: Effects Of Calpain Activity At Glutamatergic Presynaptic Sitmentioning

confidence: 99%

Calpains and neuronal damage in the ischemic brain: The swiss knife in synaptic injury

Curcio

Salazar

Mele

et al. 2016

Progress in Neurobiology

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“…Both cell types are highly susceptible to ischemic damage. 27, 56 We found that only 15% of putative ACs survived in postischemic Wt retinae, whereas the mean overall reduction of retinal cells was approximately 50% (Figures 1b and 4c). …”

Section: Discussionmentioning

confidence: 83%

“…The maintained high potassium conductance of Müller cells in the postischemic P2Y1R-KO retina may stabilize the ion and volume homeostasis, and, thereby, may prevent a cytotoxic hyperexcitation of the already energy-deprived neurons of the inner retina being highly sensitive to hyperexcitation associated with ischemia (Figure 6). 27, 56, 60 …”

Section: Discussionmentioning

confidence: 99%

Differential effects of P2Y1 deletion on glial activation and survival of photoreceptors and amacrine cells in the ischemic mouse retina

et al. 2014

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Gliosis of retinal Müller glial cells may have both beneficial and detrimental effects on neurons. To investigate the role of purinergic signaling in ischemia-induced reactive gliosis, transient retinal ischemia was evoked by elevation of the intraocular pressure in wild-type (Wt) mice and in mice deficient in the glia-specific nucleotide receptor P2Y1 (P2Y1 receptor-deficient (P2Y1R-KO)). While control retinae of P2Y1R-KO mice displayed reduced cell numbers in the ganglion cell and inner nuclear layers, ischemia induced apoptotic death of cells in all retinal layers in both, Wt and P2Y1R-KO mice, but the damage especially on photoreceptors was more pronounced in retinae of P2Y1R-KO mice. In contrast, gene expression profiling and histological data suggest an increased survival of amacrine cells in the postischemic retina of P2Y1R-KO mice. Interestingly, measuring the ischemia-induced downregulation of inwardly rectifying potassium channel (Kir)-mediated K+ currents as an indicator, reactive Müller cell gliosis was found to be weaker in P2Y1R-KO (current amplitude decreased by 18%) than in Wt mice (decrease by 68%). The inner retina harbors those neurons generating action potentials, which strongly rely on an intact ion homeostasis. This may explain why especially these cells appear to benefit from the preserved Kir4.1 expression in Müller cells, which should allow them to keep up their function in the context of spatial buffering of potassium. Especially under ischemic conditions, maintenance of this Müller cell function may dampen cytotoxic neuronal hyperexcitation and subsequent neuronal cell loss. In sum, we found that purinergic signaling modulates the gliotic activation pattern of Müller glia and lack of P2Y1 has janus-faced effects. In the end, the differential effects of a disrupted P2Y1 signaling onto neuronal survival in the ischemic retina call the putative therapeutical use of P2Y1-antagonists into question.

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“…In the same study, it was shown that GLT-1 expression was parallel to VGLUT1 expression in the caudate-putamen, suggesting the potential interplay between these two transporters in the regulation of Glu levels [182] . However, other studies did not show any changes in VGLUT1 expression after focal cerebral ischemia, while VGLUT2 and VGLUT3 mRNAs were downregulated [186] . Another study on focal cerebral ischemia demonstrated reduction in mRNA level of VGLUT1-3 in the hippocampus and cerebral cortex of young rats [187] , suggesting an age-dependent modification in VGLUTs expression.…”

Section: Vgluts In Ischemic Brainmentioning

confidence: 75%

Glutamate transporters in brain ischemia: to modulate or not?

et al. 2014

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In this review, we briefly describe glutamate (Glu) metabolism and its specific transports and receptors in the central nervous system (CNS). Thereafter, we focus on excitatory amino acid transporters, cystine/glutamate antiporters (system x c -) and vesicular glutamate transporters, specifically addressing their location and roles in CNS and the molecular mechanisms underlying the regulation of Glu transporters. We provide evidence from in vitro or in vivo studies concerning alterations in Glu transporter expression in response to hypoxia or ischemia, including limited human data that supports the role of Glu transporters in stroke patients. Moreover, the potential to induce brain tolerance to ischemia through modulation of the expression and/or activities of Glu transporters is also discussed. Finally we present strategies involving the application of ischemic preconditioning and pharmacological agents, eg β-lactam antibiotics, amitriptyline, riluzole and N-acetylcysteine, which result in the significant protection of nervous tissues against ischemia.

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Region-specific expression of vesicular glutamate and GABA transporters under various ischaemic conditions in mouse forebrain and retina

Cited by 30 publications

References 73 publications

Calpains and neuronal damage in the ischemic brain: The swiss knife in synaptic injury

Calpains and neuronal damage in the ischemic brain: The swiss knife in synaptic injury

Differential effects of P2Y1 deletion on glial activation and survival of photoreceptors and amacrine cells in the ischemic mouse retina

Glutamate transporters in brain ischemia: to modulate or not?

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