scholarly journals Effective gene expression in the rat dorsal root ganglia with a non-viral vector delivered via spinal nerve injection

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ming-Fong Chang ◽  
Jung-Hsien Hsieh ◽  
Hao Chiang ◽  
Hung-Wei Kan ◽  
Cho-Min Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Viral Vector ◽  
Spinal Nerve

scholarly journals RNAseq dataset describing transcriptional changes in cervical sensory ganglia after bilateral pyramidotomy and forelimb intramuscular gene therapy with AAV1 encoding human neurotrophin-3

2018 ◽  
Author(s):  
Claudia Kathe ◽  
Lawrence D F Moon
Keyword(s):  
Gene Expression ◽  
Dorsal Root Ganglia ◽  
Small Rnas ◽  
Dorsal Root ◽  
Viral Vector ◽  
Cervical Spinal Cord ◽  
Neurological Injury ◽  
Adult Rats ◽  
Abnormal Movements ◽  
Neurotrophin 3

AbstractUnilateral or bilateral corticospinal tract injury in the pyramids of adult rats causes changes in proprioceptive axon terminal arborization in the cervical spinal cord accompanied by hyperreflexia and abnormal movements including spasms [1, 2]. Treatment of affected forelimb muscles with an Adeno-Associated Viral Vector (AAV) encoding human neurotrophin-3 (NT3) normalizes many of these anatomical, neurophysiological and behavioural changes [1]. Interestingly, in several studies, neurotrophin-3 protein accumulates in cervical dorsal root ganglia (DRG) on the side ipsilateral to AAV injection [1, 3]. We hypothesize that neurotrophin-3 induces these changes (in proprioceptive axon wiring, proprioceptive reflex neurophysiology and sensorimotor behaviors involving proprioception) by modifying gene expression in affected cervical dorsal root ganglia (DRG). As a first step in testing this hypothesis, we analyzed the transcriptomes of cervical DRGs obtained during a previous study from naïve rats and from rats after bilateral pyramidotomy (bPYX) with unilateral intramuscular injections of either AAV1-CMV-NT3 or AAV1-CMV-EGFP made 24h after injury [1]. Ten weeks after surgery, Poly(A) RNAs and small RNAs from C6 to C8 DRGs on the treated side were sequenced. We detected mRNAs or small RNAs that were significantly regulated under three conditions (bPYX+GFP vs naïve; bPYX+NT3 versus naïve; bPYX+NT3 vs bPYX+GFP). We identified mRNAs and small RNAs whose expression level was altered after pyramidotomy and normalized by neurotrophin-3 treatment. A bioinformatic analysis enabled us to identify genes that are likely to be expressed in proprioceptors after injury and which were regulated by neurotrophin-3 in the direction expected from other datasets involving knockout or overexpression of neurotrophin-3. This dataset will help us and others identify genes in sensory neurons whose expression levels are regulated by neurotrophin-3 treatment. This may help identify novel therapeutic targets to improve sensation and movement after neurological injury. Data has been deposited in the Gene Expression Omnibus (GSE82197).

scholarly journals Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain

2020 ◽  
Author(s):  
T. Okerman ◽  
T. Jurgenson ◽  
M. Moore ◽  
A. H. Klein
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Sciatic Nerve ◽  
Signaling Pathway ◽  
Dorsal Root Ganglia ◽  
Intracellular Signaling ◽  
Dorsal Root ◽  
Morphine Tolerance ◽  
Spinal Nerve ◽  
Intracellular Signaling Pathway

AbstractBackgroundOpioid management of chronic pain can cause opioid-induced analgesic tolerance and hyperalgesia, complicating clinical pain-management treatments. Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3Kγ-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems.MethodsMorphine or saline injections were given subcutaneously twice a day for five days (15 mg/kg) to male C57Bl6 mice. A separate cohort of mice received spinal nerve ligation (SNL) one week prior to the start of morphine tolerance. Afterwards, spinal cord, dorsal root ganglia, and sciatic nerves were isolated for quantifying total and phosphorylated-JNK levels, cGMP, and gene expression analysis.ResultsGene expression for the PI3Kγ-AKT-cGMP-JNK signaling pathway including, Akt1, Akt2, Akt3, Pik3cg, Pten, Jnk3, and nNos1 were decreased in the spinal cord with varied expression changes in the dorsal root ganglia and sciatic nerve of morphine tolerant and morphine tolerant mice after SNL. We observed significant increases in total and phosphorylated-JNK levels in the spinal cord, total JNK in dorsal root ganglia, and cGMP in the sciatic nerve of morphine tolerant mice with SNL. Pharmacological inhibition of PI3K, nNOS, or JNK, using thalidomide, quercetin, or SP600125, attenuated the development of morphine tolerance in mice with SNL as measured by thermal paw withdrawal.ConclusionsOverall, the PI3K/AKT intracellular signaling pathway is a potential target for reducing the development of morphine tolerance. Continued research into this pathway will contribute to the development of new analgesic drug therapies.

scholarly journals RNA-Binding Proteins HuB, HuC, and HuD are Distinctly Regulated in Dorsal Root Ganglia Neurons from STZ-Sensitive Compared to STZ-Resistant Diabetic Mice

2019 ◽  
Vol 20 (8) ◽  
pp. 1965 ◽  
Author(s):  
Cosmin Cătălin Mustăciosu ◽  
Adela Banciu ◽  
Călin Mircea Rusu ◽  
Daniel Dumitru Banciu ◽  
Diana Savu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Transcriptional Control ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Diabetic Mice

The neuron-specific Elav-like Hu RNA-binding proteins were described to play an important role in neuronal differentiation and plasticity by ensuring the post-transcriptional control of RNAs encoding for various proteins. Although Elav-like Hu proteins alterations were reported in diabetes or neuropathy, little is known about the regulation of neuron-specific Elav-like Hu RNA-binding proteins in sensory neurons of dorsal root ganglia (DRG) due to the diabetic condition. The goal of our study was to analyze the gene and protein expression of HuB, HuC, and HuD in DRG sensory neurons in diabetes. The diabetic condition was induced in CD-1 adult male mice with single-intraperitoneal injection of streptozotocin (STZ, 150 mg/kg), and 8-weeks (advanced diabetes) after induction was quantified the Elav-like proteins expression. Based on the glycemia values, we identified two types of responses to STZ, and mice were classified in STZ-resistant (diabetic resistant, glycemia < 260 mg/dL) and STZ-sensitive (diabetic, glycemia > 260 mg/dL). Body weight measurements indicated that 8-weeks after STZ-induction of diabetes, control mice have a higher increase in body weight compared to the diabetic and diabetic resistant mice. Moreover, after 8-weeks, diabetic mice (19.52 ± 3.52 s) have longer paw withdrawal latencies in the hot-plate test than diabetic resistant (11.36 ± 1.92 s) and control (11.03 ± 1.97 s) mice, that correlates with the installation of warm hypoalgesia due to the diabetic condition. Further on, we evidenced the decrease of Elav-like gene expression in DRG neurons of diabetic mice (Elavl2, 0.68 ± 0.05 fold; Elavl3, 0.65 ± 0.01 fold; Elavl4, 0.53 ± 0.07 fold) and diabetic resistant mice (Ealvl2, 0.56 ± 0.07 fold; Elavl3, 0.32 ± 0.09 fold) compared to control mice. Interestingly, Elav-like genes have a more accentuated downregulation in diabetic resistant than in diabetic mice, although hypoalgesia was evidenced only in diabetic mice. The Elav-like gene expression changes do not always correlate with the Hu protein expression changes. To detail, HuB is upregulated and HuD is downregulated in diabetic mice, while HuB, HuC, and HuD are downregulated in diabetic resistant mice compared to control mice. To resume, we demonstrated HuD downregulation and HuB upregulation in DRG sensory neurons induced by diabetes, which might be correlated with altered post-transcriptional control of RNAs involved in the regulation of thermal hypoalgesia condition caused by the advanced diabetic neuropathy.

Induction of neuronal and myelin-related gene expression by IL-6-receptor/IL-6: A study on embryonic dorsal root ganglia cells and isolated Schwann cells

2007 ◽  
Vol 208 (2) ◽  
pp. 285-296 ◽  
Author(s):  
Pei-Lin Zhang ◽  
Alon M. Levy ◽  
Levana Ben-Simchon ◽  
Shalom Haggiag ◽  
Judith Chebath ◽  
...  
Keyword(s):  
Gene Expression ◽  
Schwann Cells ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Related Gene
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