Year: 2025
Type: article
Abstract: ABSTRACT Introduction The receptor SorCS2 is involved in the trafficking of membrane receptors and transporters. It has been implicated in brain disorders and has previously been reported to be indispensable for ionotropic glutamatergic neurotransmission in the hippocampus. Aim We aimed to study the role of SorCS2 in the control of astrocyte‐neuron communication, critical for neurovascular coupling. Methods Brain slices from P8 and 2‐month‐old wild‐type and SorCS2 knockout ( Sorcs2 −/− ) mice were immunostained for SorCS2, GFAP, AQP4, IB4, and CD31. Neurovascular coupling was assessed in vivo using laser speckle contrast imaging and ex vivo in live brain slices loaded with calcium‐sensitive dye. Bulk and cell surface fraction proteomics was analyzed on freshly isolated and cultured astrocytes, respectively, and validated with Western blot and qPCR. Results SorCS2 was strongly expressed in astrocytes, primarily in their endfeet, of P8 mice; however, it was sparsely represented in 2‐month‐old mice. Sorcs2 −/− mice demonstrated reduced neurovascular coupling associated with a reduced astrocytic calcium response to neuronal excitation. No differences in vascularization or endothelium‐dependent relaxation ex vivo between the 2‐month‐old groups were observed. Proteomics suggested changes in glutamatergic signaling and suppressed calcium signaling in Sorcs2 −/− brains from both P8 and 2‐month‐old mice. The increased abundance of glutamate metabotropic receptor 3 in Sorcs2 −/− astrocytes was validated by PCR and Western blot. In cultured Sorcs2 −/− astrocytes, AQP4 abundance was increased in the bulk lysate but reduced in the cell surface fraction, suggesting impaired trafficking. Conclusion The results suggest that SorCS2 expression is important for the development of neurovascular coupling, at least in part by modulating glutamatergic and calcium signaling in astrocytes.
Source: Acta Physiologica
DOI: 10.1111/apha.70052
Authors: Christian Staehr, Hande Login, Elizaveta V. Melnikova, Magdalena Bakun, Ewelina Ziemlinska, Lilian Kisiswa, Simin Berenji Ardestani, Stella Solveig Nolte, Hans Christian Beck, Line Mathilde Brostrup Hansen, Dmitry Postnov, Alexei Verkhratsky, Anna R. Malik, Anders Nykjaer, Vladimir V. Matchkov
Institutions: Aarhus University, Aarhus University Hospital, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Polish Academy of Sciences, University of Warsaw, Odense University Hospital, Ikerbasque, University of the Basque Country, University of Manchester, Chengdu University of Traditional Chinese Medicine, China Medical University
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,150
OpenAlex ID: W4410189902