SorCS2 Is Important for Astrocytic Function in Neurovascular Signaling

Area of Science:

• Neuroscience
• Cell Biology
• Neurophysiology

Background:

• The SorCS2 receptor plays a role in membrane receptor and transporter trafficking.
• SorCS2 is implicated in brain disorders and essential for hippocampal glutamatergic neurotransmission.

Purpose of the Study:

• To investigate SorCS2's role in astrocyte-neuron communication.
• To understand SorCS2's influence on neurovascular coupling.

Main Methods:

• Immunostaining of brain slices from wild-type and SorCS2 knockout mice.
• In vivo and ex vivo assessment of neurovascular coupling.
• Proteomic analysis of astrocytes, validated by Western blot and qPCR.

Main Results:

• SorCS2 expression in astrocytes is developmentally regulated, prominent in young mice.
• SorCS2 knockout mice exhibit impaired neurovascular coupling and reduced astrocytic calcium responses.
• Proteomics reveal altered glutamatergic and calcium signaling, with impaired AQP4 trafficking in SorCS2-deficient astrocytes.

Conclusions:

• SorCS2 is vital for the development of neurovascular coupling.
• SorCS2 modulates astrocytic glutamatergic and calcium signaling pathways.
• Impaired astrocyte-neuron communication in SorCS2 knockout mice affects brain function.