Pharmacological evaluation of rat dorsal root ganglion neurons as an in vitro model for diabetic neuropathy

Peeraer,; Meert, T. F.

doi:10.2147/jpr.s15452

Cited by 18 publications

(22 citation statements)

References 44 publications

(55 reference statements)

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“…Similarly, increased c‐fos expression has been described in superficial and deep dorsal horn neurons either after innocuous stimulation in naive animals or after noxious stimulation in nerve injury models, thus representing a widely used marker of both nociception and central sensitization . In our experimental model of OXA‐induced neuropathy, we did not detect any changes in DRG c‐fos expression, as it does not occur in another experimental model of peripheral nervous system damage, such as diabetic neuropathy …”

Section: Discussionmentioning

confidence: 99%

Anti‐allodynic and anti‐inflammatory effects of 17α‐hydroxyprogesterone caproate in oxaliplatin‐induced peripheral neuropathy

Miguel

Raggio

Villar

et al. 2019

J Peripheral Nervous Sys

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Chemotherapy‐induced peripheral neuropathy is a disabling condition induced by several frequently used chemotherapeutic drugs including the front‐line agent oxaliplatin (OXA). Symptoms are predominantly sensory with the development of neuropathic pain. Alternative dosing protocols and treatment discontinuation are the only available therapeutic strategies. The aim of our work was to evaluate the potential of a synthetic derivative of progesterone, 17α‐hydroxyprogesterone caproate (HPGC), in the prevention and treatment of OXA‐evoked painful neuropathy. We also evaluated glial activation at the dorsal root ganglia (DRG) and spinal cord levels as a possible target mechanism underlying HPGC actions. Male rats were injected with OXA and HPGC following a prophylactic (HPGCp) or therapeutic (HPGCt) scheme (starting either before or after chemotherapy). The development of hypersensitivity and allodynic pain and the expression of neuronal and glial activation markers were evaluated. When compared to control animals, those receiving OXA showed a significant decrease in paw mechanical and thermal thresholds, with the development of allodynia. Animals treated with HPGCp showed patterns of response similar to those detected in control animals, while those treated with HPGCt showed a suppression of both hypersensitivities after HPGC administration. We also observed a significant increase in the mRNA levels of activating transcription factor 3, the transcription factor (c‐fos), glial fibrillary acidic protein, ionized calcium binding adaptor protein 1, interleukin 1 beta (IL‐1β) and tumor necrosis factor alpha (TNFα) in DRG and spinal cord of OXA‐injected animals, and significantly lower levels in rats receiving OXA and HPGC. These results show that HPGC administration reduces neuronal and glial activation markers and is able to both prevent and suppress OXA‐induced allodynia, suggesting a promising therapeutic strategy.

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Section: Discussionmentioning

confidence: 99%

Anti‐allodynic and anti‐inflammatory effects of 17α‐hydroxyprogesterone caproate in oxaliplatin‐induced peripheral neuropathy

Miguel

Raggio

Villar

et al. 2019

J Peripheral Nervous Sys

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“…5). There is a clear role for palmitate in mitochondrial depolarization in many cell lineages (72)(73)(74); however, the contribution of glucose in mitochondrial depolarization of DRG neurons remains disputable (75). Studies in embryonic DRG neurons indicate that 45 mM glucose induces oxidative stress and mitochondrial dysfunction (15,16,18), whereas adult rat DRG neurons treated with up to 60 mM glucose exhibited no significant increase in neuronal oxidative stress or cell death (76,77).…”

Section: Discussionmentioning

confidence: 99%

Dyslipidemia impairs mitochondrial trafficking and function in sensory neurons

et al. 2017

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Mitochondrial trafficking plays a central role in dorsal root ganglion (DRG) neuronal cell survival and neurotransmission by transporting mitochondria from the neuronal cell body throughout the bundles of DRG axons. In type 2 diabetes (T2DM), dyslipidemia and hyperglycemia damage DRG neurons and induce mitochondrial dysfunction; however, the impact of free fatty acids and glucose on mitochondrial trafficking in DRG neurons remains unknown. To evaluate the impact of free fatty acids compared to hyperglycemia on mitochondrial transport, primary adult mouse DRG neuron cultures were treated with physiologic concentrations of palmitate and glucose and assessed for alterations in mitochondrial trafficking, mitochondrial membrane potential, and mitochondrial bioenergetics. Palmitate treatment significantly reduced the number of motile mitochondria in DRG axons, but physiologic concentrations of glucose did not impair mitochondrial trafficking dynamics. Palmitate-treated DRG neurons also exhibited a reduction in mitochondrial velocity, and impaired mitochondrial trafficking correlated with mitochondrial depolarization in palmitate-treated DRG neurons. Finally, we found differential bioenergetic effects of palmitate and glucose on resting and energetically challenged mitochondria in DRG neurons. Together, these results suggest that palmitate induces DRG neuron mitochondrial depolarization, inhibiting axonal mitochondrial trafficking and altering mitochondrial bioenergetic capacity.-Rumora, A. E., Lentz, S. I., Hinder, L. M., Jackson, S. W., Valesano, A., Levinson, G. E., Feldman, E. L. Dyslipidemia impairs mitochondrial trafficking and function in sensory neurons.

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“…Additionally, growth factors, such as the nerve growth factor and IGF‐1, L‐carnitine, and protein kinase C inhibitors, seem to be promising in the treatment of subclinical DN. The glucagon like peptide‐1 (GLP‐1) and the activation of transcription factor‐3 have been used in rat models with encouraging results.…”

Section: Treatmentmentioning

confidence: 99%

Diabetic neuropathy in children and adolescents with type 1 diabetes mellitus: Diagnosis, pathogenesis, and associated genetic markers

Kallinikou

Soldatou

Tsentidis

et al. 2019

Diabetes Metabolism Res

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Summary Diabetic neuropathy (DN) is a common long‐term complication of type 1 (T1D) and type 2 (T2D) diabetes mellitus, with significant morbidity and mortality. DN is defined as impaired function of the autonomic and/or peripheral nervous system, often subclinical, particularly in children and adolescents with T1D. Nerve conduction studies (NCS) and skin biopsies are considered gold‐standard methods in the assessment of DN. Multiple environmental and genetic factors are involved in the pathogenesis of DN. Specifically, the role of metabolic control and glycemic variability is of paramount importance. A number of recently identified genes, including the AKR1B1, VEGF, MTHFR, APOE, and ACE genes, contribute significantly in the pathogenesis of DN. These genes may serve as biomarkers to predict future DN development or treatment response. In addition, they may serve as the basis for the development of new medications or gene therapy. In this review, the diagnostic evaluation, pathogenesis, and associated genetic markers of DN in children and adolescents with T1D are presented and discussed.

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Pharmacological evaluation of rat dorsal root ganglion neurons as an in vitro model for diabetic neuropathy

Cited by 18 publications

References 44 publications

Anti‐allodynic and anti‐inflammatory effects of 17α‐hydroxyprogesterone caproate in oxaliplatin‐induced peripheral neuropathy

Anti‐allodynic and anti‐inflammatory effects of 17α‐hydroxyprogesterone caproate in oxaliplatin‐induced peripheral neuropathy

Dyslipidemia impairs mitochondrial trafficking and function in sensory neurons

Diabetic neuropathy in children and adolescents with type 1 diabetes mellitus: Diagnosis, pathogenesis, and associated genetic markers

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