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Thottumkara, A. P.

Publications and source records attributed to Thottumkara, A. P..

2 recordsLinked to original sources

Schwann cells promote sensory neuron excitability during development

Excitability--the ability to fire action potentials--is a signature feature of neurons. How neurons become excitable during development, and whether excitability is an intrinsic property of neurons or requires signaling from glial cells, remain unclear. Here we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development. We find that Schwann cells secrete prostaglandin E2, which is necessary and sufficient to induce developing somatosensory neurons to express normal levels of voltage-gated sodium channels and fire action potential trains. Inactivating this signaling pathway specifically in Schwann cells selectively impairs the maturation of nociceptor and proprioceptor somatosensory neuron subtypes, leading to corresponding sensory defects in thermoception, inflammatory pain, and proprioception. Our studies thus reveal a cell non-autonomous mechanism by which glia regulate neuronal excitability to enable the development of normal sensory functions.

neuroscience↗

SARM1 activation and its downstream pathways are distinct in neuronal compartments

Sterile alpha and TIR motif containing 1 (SARM1) is a critical regulator of axon degeneration that acts through hydrolysis of NAD+ following injury. Recent work has defined the mechanisms underlying SARM1s catalytic activity and advanced our understanding of SARM1 function in axons, yet the role of SARM1 signaling in other compartments of neurons is still not well understood. Here we show in cultured hippocampal neurons that endogenous SARM1 is present in axons, dendrites and cell bodies and that direct activation of SARM1 by the neurotoxin Vacor causes not just axon degeneration, but degeneration of all neuronal compartments. In contrast to the axon degeneration pathway defined in dorsal root ganglia (DRGs), SARM1-dependent hippocampal axon degeneration in vitro is not sensitive to calpain inhibition whereas dendrite degeneration downstream of SARM1 is calpain-dependent in this cell type. This data indicates SARM1 plays a critical role in neurodegeneration outside of axons and elucidates divergent pathways leading to degeneration in hippocampal axons and dendrites.

neuroscience↗