Biology subjects

Rittner, H. L.

Publications and source records attributed to Rittner, H. L..

3 recordsLinked to original sources

bioRxiv2025

Sex differences define the molecular and cellular phenotypes of pain resolution in dorsal root ganglia

The dorsal root ganglion (DRG), a key site for the initiation and maintenance of neuropathic pain, was examined for sex-dependent phenotypes in sensory neurons, satellite glial cells (SGCs), and local macrophages following traumatic nerve injury and during natural pain resolution. Systematic analysis of 7,495 DRG immunofluorescence images and 62 transcriptomes revealed pronounced sex-specific, multicellular DRG phenotypes, especially during pain resolution. System parameters, including tissue size and neuron density also showed sex-dependent differences. Neuropathic pain resolved without tissue or sensory neuron loss. After injury, macrophages invaded the space between sensory neurons and satellite glial cells (SGCs); this was partially reversed during pain resolution, particularly in males. In females, immune-related gene expression and macrophage phenotypes persisted longer, while SGC activation and contact to sensory neurons was more persistent in males. During resolution, synaptic and excitability-related processes were pronounced in both sexes. However, while injury responses were largely shared between sexes, the resolution phase displayed distinctly sex-specific molecular and cellular signatures. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=197 SRC="FIGDIR/small/691610v1_ufig1.gif" ALT="Figure 1"> View larger version (76K): org.highwire.dtl.DTLVardef@4063c7org.highwire.dtl.DTLVardef@156c0d2org.highwire.dtl.DTLVardef@8d4be4org.highwire.dtl.DTLVardef@7182bd_HPS_FORMAT_FIGEXP M_FIG C_FIG In briefAnalysis of [~]7,500 bioimages and 62 transcriptomes reveals pronounced sex differences in rat dorsal root ganglia during pain resolution after peripheral nerve injury. HighlightsO_LIIn both female and male rats, peripheral nerve injury and subsequent pain resolution occur in the dorsal root ganglia (DRG) without neuronal or tissue loss. C_LIO_LISex influences DRG tissue size, neuron density, immune and glial phenotypes, and molecular-cellular responses to nerve injury and pain resolution. C_LIO_LIFollowing injury, macrophages infiltrate the space between sensory neurons and satellite glial cells (SGCs); this process reverses during pain resolution, particularly in males. C_LIO_LIIn females, immune phenotypes remain more stable throughout pain resolution, while SGC contact is reduced. C_LIO_LIPain resolution involves not only the reversal of injury-induced cell changes but also the activation of resolution-specific gene programs related to synaptic signaling, neuronal excitation, and cell-cell communication. C_LIO_LISex differences on the molecular-cellular level are less prevalent after nerve injury but become prominent during pain resolution. C_LI

neuroscience↗

bioRxiv2024

Satellite glial cells from adult DRG dedifferentiate in vitro and can be reprogrammed into nociceptor-like neurons

In dorsal root ganglia (DRG), neuronal loss has been reported in patients with neuropathic pain, raising the question of whether the DRG, as part of the peripheral nervous system (PNS), harbor an endogenous cell source for neural repair. We found that adult mouse DRG harbor glial cells that dedifferentiate in vitro into Sox2/Sox10-positive glial progenitor-like cells. Coexpression of the developmental transcription factors Neurog1 and Neurog2 was sufficient to induce both neuronal and glial phenotypes. Nerve growth factor supported the maturation of a subset of neurons into nociceptor-like cells expressing functional TrpA1, TrpV1, and TTX-resistant NaV channels. We report the limitation that we miss factors allowing consistent maturation to the sensory neuron profile. In summary, in the PNS, adult DRG-derived glial cells can acquire neural progenitor-like properties, show bipotent reprogramming competence, and may serve as an intrinsic cell source for sensory circuit regeneration.

neuroscience↗

bioRxiv2023

Human dorsal root ganglia after plexus injury: either preservation or loss of the multicellular unit

ObjectivePlexus injury results in lifelong suffering of flaccid paralysis, sensory loss, and intractable pain. For this clinical problem, regenerative medicine concepts, such as cell replacement for restoring dorsal root ganglion (DRG) function, set high expectations. However, it is completely unclear which DRG cell types are affected by plexus injury. MethodsWe investigated the cellular composition of human DRG in a clinically characterized cohort of patients with plexus injury. Avulsed DRG of 13 patients were collected during reconstructive nerve surgery. Then, we analyzed the cellular composition of the DRG with a human-adapted objective deep learning-based analysis of large-scale microscopy images. ResultsSurprisingly, in about half of the patients, the injury-affected DRG no longer contained DRG cells. The complete entity of neurons, satellite glial cells, and microglia was lost and replaced by mesodermal/connective tissue. In the other half of patients, the cellular entity of the DRG was well preserved. We found no loss of neurons, no gliosis, and macrophages close to single sensory neuron/satellite glial cell entities. Patients with neuronal preservation had less pain than patients with neuronal loss. InterpretationThe findings classify plexus injury patients in two categories: type I (neuronal preservation) and type II (neuronal loss). We call for early, post-accidental interventions to protect the entire DRG and improved MRI diagnostics to detect neuronal loss. Regenerative medicine to restore DRG function will need at least two translational directions: reafferentation of existing DRG units for type I injuries; or replacement of the entire DRG structure for type II patients.

neuroscience↗