A molecular map of the human spinal dorsal and ventral horn defines arrangement of neuronal types and glial sex differences
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE318654 | GEO | 2026/02/16
REPOSITORIES: GEO
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Project description:Genes are up and down regualted in DRG and spinal dorsal cord after peripheral nerve injury WT male adult with sciatic and femoral nerve transection 7 days, RNA was purified from ipilateral or contralateral L4-L6 DRGs or lumbar spinal dorsal cords
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Project description:A molecular map of the human spinal dorsal and ventral horn defines arrangement of neuronal types and glial sex differences
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Project description:We investigated a presynaptic form of long-term potentiation (LTP) in horizontal slices of the rat spinal cord by visualizing presynaptic and postsynaptic excitation with a voltage-sensitive dye. To record presynaptic excitation, we stained primary afferent fibers anterogradely from the dorsal root. A single-pulse test stimulation of C fiber-activating strength to the dorsal root elicited action potential (AP)-like or compound AP-like optical signals throughout the superficial dorsal horn. After conditioning (240 pulses at 2 Hz for 2 min), the presynaptic excitation was augmented. Furthermore, new excitation was elicited in the areas that were silent before conditioning. For postsynaptic recording, projection neurons in spinal lamina I were stained retrogradely from the periaqueductal gray in the brain stem. The test stimulation elicited AP-like or EPSP-like optical signals in the stained neurons. After conditioning, the EPSP-like responses were augmented, and previously silent neurons were converted to active ones. Results obtained with a nitric oxide (NO) donor, NO synthase inhibitors, metabotropic glutamate receptor (mGluR) agonist and mGluR1 antagonist, and a glial metabolism inhibitor suggest that after conditioning, presynaptic excitation is facilitated by NO released from glial cells via the activation of mGluR1. The results also indicate the possible presence of additional presynaptic and postsynaptic mechanism(s) for the LTP induction. Activity-dependent LTP of nociceptive afferent synaptic transmission in the spinal cord is believed to underlie central sensitization after inflammation or nerve injury. This glial NO-mediated control of presynaptic excitation may contribute to the induction at least in part.
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2019-08-08 | GSE135539 | GEO
Project description:Here, we used joint single-nuclei RNA-sequencing (snRNA-seq) and single-nuclei ATAC sequencing (scATAC) to profile freshly isolated crypts from the human fetal intestine and matched intestinal epithelial only organoids (also known as enteroids) derived from these crypts after one passage of in vitro growth. Organoids were grown in the standard 25% LWRN media with either 100 ng/ml of EGF or 1 ng/ml of EREG added. Fresh crypts were not placed in culture but rather immediately frozen for multiomic processing.
2022-07-16 | E-MTAB-11908 | biostudies-arrayexpress
Project description:Purpose: RNAseq analysis was carried out to investigate the alterd genes by chemogenetic activation of endogenous oxytocin in the superficial layer (laminae I-II) and deep layer (laminae III-VI) of the dorsal horn. Methods: At 120 min after the s.c. administration of Saline or CNO (1 mg/kg) (n=3, each), adult male oxytocin-hM3Dq-mCherry transgenic rats were decapitated immediately without being anesthetized. Spinal cords specimens including laminae I-II and III-VI were collected separately. Results: 254 genes in the laminae I-II, and 191 genes in the laminae III-VI of the dorsal horn were significantly altered after chemogenetic activation of endogenous oxytocin.
2022-09-07 | GSE210528 | GEO
Project description:We used total RNA-sequencing (RNA-seq) to analyze ALS MN-specific gene-expression signatures in laser capture microdissected motor neurons from post-mortem lumbar spinal cords.
2016-02-01 | GSE76220 | GEO
Project description:BackgroundRobust activation of glial cells has been reported to occur particularly during the pathogenesis of bone cancer pain (BCP). Researchers from our group and others have shown that histone deacetylases (HDACs) play a significant role in modulating glia-mediated immune responses; however, it still remains unclear whether HDACs are involved in the activation of glial cells during the development of BCP.MethodsBCP model was established by intra-tibia tumor cell inoculation (TCI). The expression levels and distribution sites of histone deacetylases (HDACs) in the spinal dorsal horn and dorsal root ganglia were evaluated by Western blot and immunofluorescent staining, respectively. Suberoylanilide hydroxamic acid (SAHA), a clinically used HDAC inhibitor, was then intraperitoneally and intrathecally injected to rescue the increased expression levels of HDAC1 and HDAC2. The analgesic effects of SAHA administration on BCP were then evaluated by measuring the paw withdrawal thresholds (PWTs). The effects of SAHA on activation of glial cells and expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) in the spinal dorsal horn and dorsal root ganglia of TCI rats were further evaluated by immunofluorescent staining and Western blot analysis. Subsequently, the effects of SAHA administration on tumor growth and cancer cell-induced bone destruction were analyzed by hematoxylin and eosin (HE) staining and micro-CT scanning.ResultsTCI caused rapid and long-lasting increased expression of HDAC1/HDAC2 in glial cells of the spinal dorsal horn and dorsal root ganglia. Inhibiting HDACs by SAHA not only reversed TCI-induced upregulation of HDACs but also inhibited the activation of glial cells in the spinal dorsal horn and dorsal root ganglia, and relieved TCI-induced mechanical allodynia. Further, we found that SAHA administration could not prevent cancer infiltration or bone destruction in the tibia, which indicated that the analgesic effects of SAHA were not due to its anti-tumor effects. Moreover, we found that SAHA administration could inhibit GSK3β activity in the spinal dorsal horn and dorsal root ganglia, which might contributed to the relief of BCP.ConclusionOur findings suggest that HDAC1 and HDAC2 are involved in the glia-mediated neuroinflammation in the spinal dorsal horn and dorsal root ganglia underlying the pathogenesis of BCP, which indicated that inhibiting HDACs by SAHA might be a potential strategy for pain relief of BCP.
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Project description:IntroductionInflammation and nerve injury promote astrocyte activation, which regulates the development and resolution of pain, in the spinal dorsal horn. APOE regulates lipid metabolism and is predominantly expressed in the astrocytes. However, the effect of astrocytic APOE and lipid metabolism on spinal cellular function is unclear. This study aimed to investigate the effect of spinal Apoe on spinal cellular functions using the complete Freund's adjuvant (CFA)-induced inflammatory pain mouse model.MethodsAfter intraplantar injection of CFA, we assessed pain behaviors in C57BL6 and Apoe knockout (Apoe-/-) mice using von Frey and Hargreaves' tests and analyzed dorsal horn samples (L4-5) using western blotting, immunofluorescence, quantitative real-time polymerase chain reaction, and RNA sequencing.ResultsThe Apoe levels were markedly upregulated at 2 h and on days 1 and 3 post-CFA treatment. Apoe was exclusively expressed in the astrocytes. Apoe-/- mice exhibited decreased pain on day 1, but not at 2 h, post-CFA treatment. Apoe-/- mice also showed decreased spinal neuron excitability and paw edema on day 1 post-CFA treatment. Global transcriptomic analysis of the dorsal horn on day 1 post-CFA treatment revealed that the differentially expressed mRNAs in Apoe-/- mice were associated with lipid metabolism and the immune system. Astrocyte activation was impaired in Apoe-/- mice on day 1 post-CFA treatment. The intrathecal injection of Apoe antisense oligonucleotide mitigated CFA-induced pain hypersensitivity.ConclusionsApoe deficiency altered lipid metabolism in astrocytes, exerting regulatory effects on immune response, astrocyte activation, and neuronal activity and consequently disrupting the maintenance of inflammatory pain after peripheral inflammation. Targeting APOE is a potential anti-nociception and anti-inflammatory strategy.
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Project description:Persistent mechanical hypersensitivity that occurs in the setting of injury or disease remains a major clinical problem largely because the underlying neural circuitry is still not known. Here we report the functional identification of key components of the elusive dorsal horn circuit for mechanical allodynia. We show that the transient expression of VGLUT3 by a discrete population of neurons in the deep dorsal horn is required for mechanical pain and that activation of the cells in the adult conveys mechanical hypersensitivity. The cells, which receive direct low threshold input, point to a novel location for circuit initiation. Subsequent analysis of c-Fos reveals the circuit extends dorsally to nociceptive lamina I projection neurons, and includes lamina II calretinin neurons, which we show also convey mechanical allodynia. Lastly, using inflammatory and neuropathic pain models, we show that multiple microcircuits in the dorsal horn encode this form of pain.
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