Unspecific labelling of oligodendrocytes by sulforhodamine 101 depends on astrocytic uptake via the thyroid hormone transporter OATP1C1 (SLCO1C1)

Hagos, Liya; Hülsmann, Swen

doi:10.1016/j.neulet.2016.08.010

Cited by 18 publications

(16 citation statements)

References 29 publications

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“…However, modified ACSF used during SR-101 incubation included 6 mM Mg 2+ , and TTX, NBQX, and AP5 had no appreciable effects on astrocyte or neuronal volume changes. SR-101 labeling specificity is another, more recent concern (Hill and Grutzendler, 2014 ; Hagos and Hülsmann, 2016 ). Based on patch-clamp analysis of SR-101 labeled cells, we have observed that ~87% of SR-101-labeled cells are astrocytes based on their electrophysiological parameters, indicating that SR-101 is highly reliable as an astrocyte marker for our purposes.…”

Section: Methodsmentioning

confidence: 99%

Hippocampal and Cortical Pyramidal Neurons Swell in Parallel with Astrocytes during Acute Hypoosmolar Stress

Murphy

Davila

Cuvelier

et al. 2017

Front. Cell. Neurosci.

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Normal nervous system function is critically dependent on the balance of water and ions in the extracellular space (ECS). Pathological reduction in brain interstitial osmolarity results in osmotically-driven flux of water into cells, causing cellular edema which reduces the ECS and increases neuronal excitability and risk of seizures. Astrocytes are widely considered to be particularly susceptible to cellular edema due to selective expression of the water channel aquaporin-4 (AQP4). The apparent resistance of pyramidal neurons to osmotic swelling has been attributed to lack of functional water channels. In this study we report rapid volume changes in CA1 pyramidal cells in hypoosmolar ACSF (hACSF) that are equivalent to volume changes in astrocytes across a variety of conditions. Astrocyte and neuronal swelling was significant within 1 min of exposure to 17 or 40% hACSF, was rapidly reversible upon return to normosmolar ACSF, and repeatable upon re-exposure to hACSF. Neuronal swelling was not an artifact of patch clamp, occurred deep in tissue, was similar at physiological vs. room temperature, and occurred in both juvenile and adult hippocampal slices. Neuronal swelling was neither inhibited by TTX, nor by antagonists of NMDA or AMPA receptors, suggesting that it was not occurring as a result of excitotoxicity. Surprisingly, genetic deletion of AQP4 did not inhibit, but rather augmented, astrocyte swelling in severe hypoosmolar conditions. Taken together, our results indicate that neurons are not osmoresistant as previously reported, and that osmotic swelling is driven by an AQP4-independent mechanism.

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Section: Methodsmentioning

confidence: 99%

Hippocampal and Cortical Pyramidal Neurons Swell in Parallel with Astrocytes during Acute Hypoosmolar Stress

Murphy

Davila

Cuvelier

et al. 2017

Front. Cell. Neurosci.

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“…SR101 may increase neuronal activity in hippocampal slices (Kang et al, 2010), and induce seizure-like activity in vivo in mouse cortex when using concentrations of 0.05 mM, but do not affect activity at lower concentrations (Rasmussen et al, 2016;Hulsmann et al, 2017). Furthermore, it has been shown both in slices and in vivo that cortical oligodendrocytes may take up SR101 (Hill and Grutzendler, 2014;Hagos and Hulsmann, 2016). We used a 10 times lower concentration of SR101 than the suggested threshold for effects on neuronal activity and uptake by oligodendrocytes.…”

Section: Discussionmentioning

confidence: 99%

Spontaneous astrocytic Ca²⁺ activity abounds in electrically suppressed ischemic penumbra of aged mice

Fordsmann

Murmu

Cai

et al. 2018

Glia

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Experimental focal cortical ischemic lesions consist of an ischemic core and a potentially salvageable peri‐ischemic region, the ischemic penumbra. The activity of neurons and astrocytes is assumed to be suppressed in the penumbra because the electrical function is interrupted, but this is incompletely elucidated. Most experimental stroke studies used young adult animals, whereas stroke is prevalent in the elderly population. Using two‐photon imaging in vivo, we here demonstrate extensive but electrically silent, spontaneous Ca2+ activity in neurons and astrocytes in the ischemic penumbra of 18‐ to 24‐month‐old mice 2–4 hr after middle cerebral artery occlusion. In comparison, stroke reduced spontaneous Ca2+ activity in neurons and astrocytes in adult mice (3–4 months of age). In aged mice, stroke increased astrocytic spontaneous Ca2+ activity considerably while neuronal spontaneous Ca2+ activity was unchanged. Blockade of action potentials and of purinergic receptors strongly reduced spontaneous Ca2+ activity in both neurons and astrocytes in the penumbra of old stroke mice. This indicates that stroke had a direct influence on mechanisms in presynaptic terminals and on purinergic signaling. Thus, highly dynamic variations in spontaneous Ca2+ activity characterize the electrically compromised penumbra, with remarkable differences between adult and old mice. The data are consistent with the notion that aged neurons and astrocytes take on a different phenotype than young mice. The increased activity of the aged astrocyte phenotype may be harmful to neurons. We suggest that the abundant spontaneous Ca2+ activity in astrocytes in the ischemic penumbra of old mice may be a novel target for neuroprotection strategies. A video abstract of this article can be found at https://youtu.be/AKlwKFsz1qE.

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“…Sulforhodamine 101 targets astrocytes by specific uptake through an organic anion‐transport protein. Although it successfully labels astrocytes in rat hippocampal slice cultures and the mouse cortex in vivo, it also labels oligodendrocytes, another type of glial cell in the brain, by traveling through gap junctions from labeled astrocytes . Furthermore, there have been no reported analogues of sulforhodamine 101 that improve its astrocyte‐targeting ability or alter its optical properties.…”

Section: Methodsmentioning

confidence: 99%

Design Principles for Cationic, Astrocyte‐Targeted Probes

et al. 2019

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The brain's astrocytes play key roles in normal and pathological brain processes. Targeting small molecules to astrocytes in the presence of the many other cell types in the brain will provide useful tools for their visualization and manipulation. Herein, we explore the functional consequences of synthetic modifications to a recently described astrocyte marker composed of a bright rhodamine‐based fluorophore and an astrocyte‐targeting moiety. We altered the nature of the targeting moiety to probe the dependence of astrocyte targeting on hydrophobicity, charge, and pKa when exposed to astrocytes and neurons isolated from the mouse cortex. We found that an overall molecular charge of +2 and a targeting moiety with a heterocyclic aromatic amine are important requirements for specific and robust astrocyte labeling. These results provide a basis for engineering astrocyte‐targeted molecular tools with unique properties, including metabolite sensing or optogenetic control.

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Unspecific labelling of oligodendrocytes by sulforhodamine 101 depends on astrocytic uptake via the thyroid hormone transporter OATP1C1 (SLCO1C1)

Cited by 18 publications

References 29 publications

Hippocampal and Cortical Pyramidal Neurons Swell in Parallel with Astrocytes during Acute Hypoosmolar Stress

Hippocampal and Cortical Pyramidal Neurons Swell in Parallel with Astrocytes during Acute Hypoosmolar Stress

Spontaneous astrocytic Ca²⁺ activity abounds in electrically suppressed ischemic penumbra of aged mice

Design Principles for Cationic, Astrocyte‐Targeted Probes

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Unspecific labelling of oligodendrocytes by sulforhodamine 101 depends on astrocytic uptake via the thyroid hormone transporter OATP1C1 (SLCO1C1)

Cited by 18 publications

References 29 publications

Hippocampal and Cortical Pyramidal Neurons Swell in Parallel with Astrocytes during Acute Hypoosmolar Stress

Hippocampal and Cortical Pyramidal Neurons Swell in Parallel with Astrocytes during Acute Hypoosmolar Stress

Spontaneous astrocytic Ca2+ activity abounds in electrically suppressed ischemic penumbra of aged mice

Design Principles for Cationic, Astrocyte‐Targeted Probes

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Spontaneous astrocytic Ca²⁺ activity abounds in electrically suppressed ischemic penumbra of aged mice