PURINERGIC SIGNALING IN ASTROCYTIC CA²⁺ DYNAMICS OF THE SPINAL CORD

Astrocytes are highly heterogeneous glial cells whose functional properties vary across regions of the central nervous system. Although astrocytic purinergic signaling has been extensively studied in the brain, its functional signaling properties and pathological remodeling in the spinal cord remain poorly understood. In particular, astrocytic calcium (Ca²⁺) and cyclic AMP (cAMP) signaling pathways have been implicated in the regulation of gliosis and neuron–glia communication, yet their roles in spinal cord neuroinflammation are largely unexplored.
Here, we characterize mouse spinal cord astrocytes with a focus on purinergic signaling under physiological and neuroinflammatory conditions. Using pharmacological approaches in acute spinal cord tissue, we identify a distinct purinergic signaling profile in astrocytes of the dorsal horn, indicating pronounced regional specialization within the central nervous system. To investigate the functional consequences of this specialization, we employ genetically encoded calcium indicators selectively expressed in astrocytes and perform confocal imaging to characterize Ca²⁺ responses evoked by pharmacological activation of purinergic receptors. Astrocytic calcium signals are robustly induced by ADP, UDP, and UTP, indicating functional expression of metabotropic purinergic receptors. Pharmacological dissection suggests differential receptor contributions, with ADP-evoked responses consistent with P2Y13 receptor signaling, while UTP- and UDP-evoked responses predominantly involve P2Y4 and P2Y6 receptors.
Immunohistochemical analyses further reveal pronounced astrogliosis and gliosis in a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), highlighting substantial astrocytic remodeling during neuroinflammation. Ongoing analyses compare astrocytic calcium signaling in healthy and EAE spinal cord tissue to determine how inflammatory conditions reshape intracellular signaling dynamics.
DFG-SFB1328 A07, #404539526