Biology subjects

Ahlgreen, O. A.

Publications and source records attributed to Ahlgreen, O. A..

3 recordsLinked to original sources

bioRxiv2025

Meteorin resolves nociceptive hypersensitivity by reducing connexin-mediated coupling in satellite glial cells

Neuropathic pain, a persistent condition arising from injury to the nervous system, involves complex interactions between neurons and non-neuronal cells, including satellite glial cells (SGCs) in the dorsal root ganglia (DRG). In this study, we examined the glial-targeting effects of meteorin, a neurotrophic protein with gliogenic properties, using mouse models of neuropathic and inflammatory pain. Systemic meteorin administration reversed mechanical hypersensitivity across diverse neuropathic and inflammatory pain models, with therapeutic effects persisting beyond the treatment period. We identified SGCs as the principal site of meteorin expression and action in the DRG, where it selectively activated SGCs and altered their functional state. Proteomic profiling revealed meteorin-mediated downregulation of gap junction proteins in SGCs, particularly connexin 43, which was corroborated by immunohistochemical analyses. Functional assessments demonstrated that meteorin treatment normalized injury-induced increases in intercellular coupling between SGCs, establishing a mechanistic link between glial network modulation and pain resolution. These findings identify meteorin as a regulator of SGC communication through connexin-dependent mechanisms. The sustained therapeutic effects and multi-model efficacy highlight meteorin as a potential intervention for neuropathic pain while advancing our understanding of SGC plasticity in sensory processing.

neuroscience↗

bioRxiv2025

Mapping satellite glial cell heterogeneity reveals distinct spatial organization and signifies functional diversity in the dorsal root ganglion

Satellite glial cells (SGCs) envelop the somata, axon hillock, and initial axon segment of sensory neurons in the dorsal root ganglia (DRG), playing a critical role in regulating the neuronal microenvironment. While DRG neurons have been extensively studied and classified based on size, molecular markers, and functional characteristics, very little is still known about SGC heterogeneity and its potential implications on sensory processing in the DRG. Single cell transcriptional analyses have proposed the existence of SGC subtypes, yet in situ validation, spatial distribution, and potential functional implications of such subtypes are still largely unexplored. Here, we present the first comprehensive in situ characterization of SGC heterogeneity within the mouse DRG. By integrating single-cell RNA sequencing with immunohistochemistry, in situ hybridization, and advanced imaging techniques, distinct SGC subclusters were identified, validated, and spatially mapped within their native anatomical context. We visually identify four distinct subpopulations: 1) a predominant population of perisomatic SGC sheaths defined by the expression of marker proteins traditionally used to characterize the entire SGC population, including FABP7, KIR4.1, GS, and CX43. 2) OCT6+ SGCs occasionally being found in mosaic perisomatic sheaths, and consistently associated with axonal glomeruli, primarily ensheathing initial segment axon. 3) SCN7A+ SGCs, exhibiting no/low expression of traditional SGC markers and forming specialized homogenous sheaths around non-peptidergic neuron subtypes, implicating their potential role in pruritic (itch-related) conditions. 4) Interferon response gene-expressing SGCs, responding to Herpes Simplex Virus infection, suggesting potential involvement in antiviral protection. Finally, we investigate human DRG and find an inner perisomatic SGC layer surrounded by an outer SGC layer, with traditional and novel markers distinctively distributed between the two layers. Our results provide novel insight into SGC heterogeneity in the DRG and suggests distinct functional properties for such subtypes of relevance for the neuronal microenvironment.

neuroscience↗

bioRxiv2024

Bradykinesia and postural instability in a model of prodromal Synucleinopathy with alpha-Synuclein aggregation in the gigantocellular nuclei.

-Synuclein (aSyn) accumulation within the extra-nigral neuronal populations in brainstem, including the gigantocellular nuclei (GRN/Gi) of reticular formation, is a recognized feature during the prodromal phase of Parkinson disease (PD). Accordingly, there is a burgeoning interest in animal model development for understanding the pathological significance of extra-nigral synucleinopathy, in relation to motor and/or non-motor symptomatology in PD. Here, we report an experimental paradigm for the induction of aSyn aggregation in brainstem, with stereotaxic delivery of pre-formed fibrillar (PFF) aSyn in the pontine GRN of transgenic mice expressing the mutant human Ala53Thr aSyn (M83 line). Our data show that PFF aSyn-induced aggregate pathology in GRN leads to progressive decline in spontaneous locomotion and an early phenotype of postural instability. This early phase of bradykinesia was followed by a moribund stage, characterized by worsening motor performance and impaired survival with substantial aSyn aggregation in several brain regions beyond the GRN. Collectively, our observations suggest an experimental framework for studying the pathological significance of aSyn aggregation in GRN in relation to features of movement disability in PD. With further refinements, we anticipate that this model holds promise as a test-bed for translational research in PD and related disorders.

neuroscience↗