Biology subjects

Prudente, A. S.

Publications and source records attributed to Prudente, A. S..

2 recordsLinked to original sources

bioRxiv2026

Sympathetic Control of Sensory Neuron Fate and Function

Sensory neurons in the dorsal root ganglia (DRG) serve as conduits for transmitting peripheral stimuli to the central nervous system, playing an essential role in sensory perception and coordinated movement. This study reveals that sympathetic innervation is critical for these neurons survival and functional integrity. Using a surgical microsympathectomy model in mice, we found that targeted sympathetic denervation of the lumbar DRGs triggered robust neuronal death, peaking four days post-surgery. This cellular loss is evidenced by reduced spinal projections, decreased nerve density in the skin, and impaired sensory and motor functions. We further identified norepinephrine (NE) as a vital neuroprotective agent; continuous NE supplementation effectively prevented cell death. Additionally, macrophage activation following denervation proved protective, as macrophage depletion exacerbated neuronal loss. It is suggested that the loss of sympathetic input disrupted mitochondrial homeostasis, releasing Smac/DIABLO, activating Caspase-3, and leading to cell death. These findings highlight the sympathetic nervous systems novel role in maintaining sensory neuron viability through tonic adrenergic support.

neuroscience↗

bioRxiv2023

Peripheral gating of pain by glial endozepine

We report that diazepam binding inhibitor (DBI) is a glial messenger mediating satellite glia-sensory neuron crosstalk in the dorsal root ganglion (DRG). DBI is highly and specifically expressed in satellite glia cells (SGCs) of mice, rat and human, but not in sensory neurons or other DRG-resident cells. Knockdown of DBI results in a robust mechanical hypersensitivity without significant effects on other sensory modalities. In vivo overexpression of DBI in SGCs reduces sensitivity to mechanical stimulation and alleviates mechanical allodynia in neuropathic and inflammatory pain models. We further show that DBI acts as a partial agonist and positive allosteric modulator at the neuronal GABAA receptors, particularly strongly effecting those with a high-affinity benzodiazepine binding site. Such receptors are selectively expressed by a subpopulation of mechanosensitive DRG neurons and these are also more enwrapped with DBI-expressing glia, as compared to other DRG neurons, suggesting a mechanism for specific effect of DBI on mechanosensation. These findings identified a new, peripheral neuron-glia communication mechanism modulating pain signalling, which can be targeted therapeutically.

neuroscience↗