SorCS2 modulates neurovascular coupling via glutamatergic and calcium signaling in astrocytes

Christian  Staehr; Hande Login; Dmitry Postnov; Simin Berenji Ardestani; Stella Solveig Nolte; Hans Christian Beck; Anders Nykjær; Vladimir Matchkov

doi:10.1101/2023.02.16.528727

SorCS2 modulates neurovascular coupling via glutamatergic and calcium signaling in astrocytes

Christian Staehr, Hande Login, Dmitry Postnov, Simin Berenji Ardestani, Stella Solveig Nolte, Hans Christian Beck, Anders Nykjær, Vladimir Matchkov

Publikation: Working paper/Preprint › Preprint

Abstract

SorCS2 is involved in trafficking of membrane receptors and transporters. SorCS2 is implicated in brain disorders, but the mechanism remains uncertain. We hypothesized that SorCS2 expression is important for neurovascular coupling.

Brains from P8 and 2-month-old wild type mice were stained for SorCS2 and compared to SorCS2 knockouts (Sorcs2-/-). Changes in cerebral perfusion in response to sensory stimulation, i.e., neurovascular coupling, were compared in vivo. Neurovascular coupling was also assessed ex vivo in brain slices loaded with calcium-sensitive dye. Proteomics of astrocytes was analyzed for ingenuity pathways.

SorCS2 was strongly expressed in astrocytic endfeet of P8 mice but only in few astrocytes from 2-month-old brains. Sorcs2-/- mice demonstrated reduced neurovascular coupling. This was associated with reduced astrocytic calcium response to neuronal excitation in Sorcs2-/- mice. No difference in cerebral artery caliber nor in endothelial function was seen between wild type and Sorcs2-/- mice. Proteomics indicated reduced glutamatergic signaling and suppressed calcium signaling in Sorcs2-/- astrocytes.

We suggest that SorCS2 expression is important for neurovascular coupling due to modulation of glutamatergic and calcium signaling in astrocytes.

Originalsprog	Engelsk
Udgiver	bioRxiv
DOI	https://doi.org/10.1101/2023.02.16.528727
Status	Udgivet - 16 feb. 2023

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10.1101/2023.02.16.528727Licens: CC BY-NC-ND

Citationsformater

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abstract = "SorCS2 is involved in trafficking of membrane receptors and transporters. SorCS2 is implicated in brain disorders, but the mechanism remains uncertain. We hypothesized that SorCS2 expression is important for neurovascular coupling.Brains from P8 and 2-month-old wild type mice were stained for SorCS2 and compared to SorCS2 knockouts (Sorcs2-/-). Changes in cerebral perfusion in response to sensory stimulation, i.e., neurovascular coupling, were compared in vivo. Neurovascular coupling was also assessed ex vivo in brain slices loaded with calcium-sensitive dye. Proteomics of astrocytes was analyzed for ingenuity pathways.SorCS2 was strongly expressed in astrocytic endfeet of P8 mice but only in few astrocytes from 2-month-old brains. Sorcs2-/- mice demonstrated reduced neurovascular coupling. This was associated with reduced astrocytic calcium response to neuronal excitation in Sorcs2-/- mice. No difference in cerebral artery caliber nor in endothelial function was seen between wild type and Sorcs2-/- mice. Proteomics indicated reduced glutamatergic signaling and suppressed calcium signaling in Sorcs2-/- astrocytes.We suggest that SorCS2 expression is important for neurovascular coupling due to modulation of glutamatergic and calcium signaling in astrocytes.",

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AU - Login, Hande

AU - Postnov, Dmitry

AU - Berenji Ardestani, Simin

AU - Nolte, Stella Solveig

AU - Beck, Hans Christian

AU - Nykjær, Anders

AU - Matchkov, Vladimir

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N2 - SorCS2 is involved in trafficking of membrane receptors and transporters. SorCS2 is implicated in brain disorders, but the mechanism remains uncertain. We hypothesized that SorCS2 expression is important for neurovascular coupling.Brains from P8 and 2-month-old wild type mice were stained for SorCS2 and compared to SorCS2 knockouts (Sorcs2-/-). Changes in cerebral perfusion in response to sensory stimulation, i.e., neurovascular coupling, were compared in vivo. Neurovascular coupling was also assessed ex vivo in brain slices loaded with calcium-sensitive dye. Proteomics of astrocytes was analyzed for ingenuity pathways.SorCS2 was strongly expressed in astrocytic endfeet of P8 mice but only in few astrocytes from 2-month-old brains. Sorcs2-/- mice demonstrated reduced neurovascular coupling. This was associated with reduced astrocytic calcium response to neuronal excitation in Sorcs2-/- mice. No difference in cerebral artery caliber nor in endothelial function was seen between wild type and Sorcs2-/- mice. Proteomics indicated reduced glutamatergic signaling and suppressed calcium signaling in Sorcs2-/- astrocytes.We suggest that SorCS2 expression is important for neurovascular coupling due to modulation of glutamatergic and calcium signaling in astrocytes.

AB - SorCS2 is involved in trafficking of membrane receptors and transporters. SorCS2 is implicated in brain disorders, but the mechanism remains uncertain. We hypothesized that SorCS2 expression is important for neurovascular coupling.Brains from P8 and 2-month-old wild type mice were stained for SorCS2 and compared to SorCS2 knockouts (Sorcs2-/-). Changes in cerebral perfusion in response to sensory stimulation, i.e., neurovascular coupling, were compared in vivo. Neurovascular coupling was also assessed ex vivo in brain slices loaded with calcium-sensitive dye. Proteomics of astrocytes was analyzed for ingenuity pathways.SorCS2 was strongly expressed in astrocytic endfeet of P8 mice but only in few astrocytes from 2-month-old brains. Sorcs2-/- mice demonstrated reduced neurovascular coupling. This was associated with reduced astrocytic calcium response to neuronal excitation in Sorcs2-/- mice. No difference in cerebral artery caliber nor in endothelial function was seen between wild type and Sorcs2-/- mice. Proteomics indicated reduced glutamatergic signaling and suppressed calcium signaling in Sorcs2-/- astrocytes.We suggest that SorCS2 expression is important for neurovascular coupling due to modulation of glutamatergic and calcium signaling in astrocytes.

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