Neuropathological changes in dorsal root ganglia induced by pyridoxine in dogs

Abstract Background: Pyridoxine (PDX), vitamin B6, is an essential vitamin. PDX deficiency induces various symptoms and abuse of PDX supplement also acts as a neurotoxicant that induces severe sensory neuropathy. Results: To assess the possibility of reversible sensory neuropathy model using dogs, 150 mg/kg pyridoxine (PDX) was injected subcutaneously into dogs for seven days and body weight measurement, postural reaction assessments, and electrophysiological recordings were conducted. In addition, the morphology of dorsal root ganglia (DRG) and changes of glial fibrillary acidic protein (GFAP) immunoreactive satellite glial cells and ionized calcium-binding adapter molecule 1 (Iba-1) immunoreactive microglia/macrophages were observed at 0, 1 and 4 weeks after the last PDX treatment. During the administration period, body weight loss and proprioceptive loss occurred. After the treatments were completed, electrophysiological recordings showed that the H-reflex of the treated dogs had disappeared at week 0. These phenomena persisted for four weeks exceptional body weight. CV and HE staining revealed that neurons in DRG had significant loss of large-sized neurons 0 and 1 week, but these neurons were recovered 4 weeks. Iba-1 and GFAP immunohistochemistry showed that reactive microglia/macrophages and satellite glial cells were pronounced at 0 and 1 weeks after the last PDX treatment, respectively and thereafter decreased with time after PDX treatment, respectively.Conclusions: This result suggests that PDX-induced neuropathy model is reversible and can be a good experimental model for research on neuropathy in dogs.

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Neuropathological changes in dorsal root ganglia induced by pyridoxine in dogs

10.21203/rs.2.17162/v3 ◽

2020 ◽

Author(s):

Sumin Yun ◽

Woosuk Kim ◽

Min Soo Kang ◽

Tae Hyeong Kim ◽

Yoonhwan Kim ◽

...

Keyword(s):

Body Weight ◽

Dorsal Root Ganglia ◽

Calcium Binding ◽

Dorsal Root ◽

Sensory Neuropathy ◽

Post Treatment ◽

Treatment Level ◽

Reactive Microglia ◽

Satellite Glial Cells ◽

Electrophysiological Recordings

Abstract Background: Pyridoxine (PDX; vitamin B6), is an essential vitamin. PDX deficiency induces various symptoms, and when PDX is misused it acts as a neurotoxicant, inducing severe sensory neuropathy. Results: To assess the possibility of creating a reversible sensory neuropathy model using dogs, 150 mg/kg of PDX was injected subcutaneously into dogs for seven days and body weight measurements, postural reaction assessments, and electrophysiological recordings were obtained. In addition, the morphology of dorsal root ganglia (DRG) and changes in glial fibrillary acidic protein (GFAP) immunoreactive satellite glial cells and ionized calcium-binding adapter molecule 1 (Iba-1) immunoreactive microglia/macrophages were assessed at 1 day, 1 week, and 4 weeks after the last PDX treatment. During the administration period, body weight and proprioceptive losses occurred. One day after the last PDX treatment, electrophysiological recordings showed the absence of the H-reflex in the treated dogs. These phenomena persisted over the four post-treatment weeks, with the exception of body weight which recovered to the pre-treatment level. Staining (CV and HE) results revealed significant losses of large-sized neurons in the DRG at 1 day and 1 week after PDX treatment cessation, but the losses were recovered at 4 weeks post-treatment. The Iba-1 and GFAP immunohistochemistry results showed pronounced increases in reactive microglia/macrophage and satellite glial cell at 1 day and 1 week, respectively, after the last PDX treatment, and thereafter, immunoreactivity decreased with increasing time after PDX treatment. Conclusions: The results suggest that PDX-induced neuropathy is reversible in dogs; thus, dogs can be considered a good experimental model for research on neuropathy.

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Neuropathological changes in dorsal root ganglia induced by pyridoxine in dogs

10.21203/rs.2.17162/v5 ◽

2020 ◽

Author(s):

Sumin Yun ◽

Woosuk Kim ◽

Min Soo Kang ◽

Tae Hyeong Kim ◽

Yoonhwan Kim ◽

...

Keyword(s):

Body Weight ◽

Dorsal Root Ganglia ◽

Calcium Binding ◽

Dorsal Root ◽

Sensory Neuropathy ◽

Post Treatment ◽

Treatment Level ◽

Reactive Microglia ◽

Satellite Glial Cells ◽

Electrophysiological Recordings

Abstract Background: Pyridoxine (PDX; vitamin B 6 ), is an essential vitamin. PDX deficiency induces various symptoms, and when PDX is misused it acts as a neurotoxicant, inducing severe sensory neuropathy. Results: To assess the possibility of creating a reversible sensory neuropathy model using dogs, 150 mg/kg of PDX was injected subcutaneously into dogs for seven days and body weight measurements, postural reaction assessments, and electrophysiological recordings were obtained. In addition, the morphology of dorsal root ganglia (DRG) and changes in glial fibrillary acidic protein (GFAP) immunoreactive satellite glial cells and ionized calcium-binding adapter molecule 1 (Iba-1) immunoreactive microglia/macrophages were assessed at 1 day, 1 week, and 4 weeks after the last PDX treatment. During the administration period, body weight and proprioceptive losses occurred. One day after the last PDX treatment, electrophysiological recordings showed the absence of the H-reflex in the treated dogs. These phenomena persisted over the four post-treatment weeks, with the exception of body weight which recovered to the pre-treatment level. Staining (CV and HE) results revealed significant losses of large-sized neurons in the DRG at 1 day and 1 week after PDX treatment cessation, but the losses were recovered at 4 weeks post-treatment. The Iba-1 and GFAP immunohistochemistry results showed pronounced increases in reactive microglia/macrophage and satellite glial cell at 1 day and 1 week, respectively, after the last PDX treatment, and thereafter, immunoreactivity decreased with increasing time after PDX treatment. Conclusions: The results suggest that PDX-induced neuropathy is reversible in dogs; thus, dogs can be considered a good experimental model for research on neuropathy.

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Neuropathological changes in dorsal root ganglia induced by pyridoxine in dogs

10.21203/rs.2.17162/v4 ◽

2020 ◽

Author(s):

Sumin Yun ◽

Woosuk Kim ◽

Min Soo Kang ◽

Tae Hyeong Kim ◽

Yoonhwan Kim ◽

...

Keyword(s):

Body Weight ◽

Dorsal Root Ganglia ◽

Calcium Binding ◽

Dorsal Root ◽

Sensory Neuropathy ◽

Post Treatment ◽

Treatment Level ◽

Reactive Microglia ◽

Satellite Glial Cells ◽

Electrophysiological Recordings

Abstract Background: Pyridoxine (PDX; vitamin B 6 ), is an essential vitamin. PDX deficiency induces various symptoms, and when PDX is misused it acts as a neurotoxicant, inducing severe sensory neuropathy. Results: To assess the possibility of creating a reversible sensory neuropathy model using dogs, 150 mg/kg of PDX was injected subcutaneously into dogs for seven days and body weight measurements, postural reaction assessments, and electrophysiological recordings were obtained. In addition, the morphology of dorsal root ganglia (DRG) and changes in glial fibrillary acidic protein (GFAP) immunoreactive satellite glial cells and ionized calcium-binding adapter molecule 1 (Iba-1) immunoreactive microglia/macrophages were assessed at 1 day, 1 week, and 4 weeks after the last PDX treatment. During the administration period, body weight and proprioceptive losses occurred. One day after the last PDX treatment, electrophysiological recordings showed the absence of the H-reflex in the treated dogs. These phenomena persisted over the four post-treatment weeks, with the exception of body weight which recovered to the pre-treatment level. Staining (CV and HE) results revealed significant losses of large-sized neurons in the DRG at 1 day and 1 week after PDX treatment cessation, but the losses were recovered at 4 weeks post-treatment. The Iba-1 and GFAP immunohistochemistry results showed pronounced increases in reactive microglia/macrophage and satellite glial cell at 1 day and 1 week, respectively, after the last PDX treatment, and thereafter, immunoreactivity decreased with increasing time after PDX treatment. Conclusions: The results suggest that PDX-induced neuropathy is reversible in dogs; thus, dogs can be considered a good experimental model for research on neuropathy.

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Neuropathological changes in dorsal root ganglia induced by pyridoxine in dogs

10.21203/rs.2.17162/v1 ◽

2019 ◽

Author(s):

Sumin Yun ◽

Woosuk Kim ◽

Min Soo Kang ◽

Tae Hyeong Kim ◽

Yoonhwan Kim ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Body Weight Loss ◽

Sensory Neuropathy ◽

Significant Loss ◽

Vitamin B ◽

Satellite Glial Cells ◽

Electrophysiological Recordings

Abstract Background: Pyridoxine (PDX), vitamin B 6 , is an essential vitamin. PDX deficiency induces various symptoms and abuse of PDX supplement also acts as a neurotoxicant that induces severe sensory neuropathy. Results: To construct a sensory neuropathy model in dogs, excess pyridoxine (PDX) was injected subcutaneously into dogs for seven days and dorsal root ganglia (DRG) were observed at 0, 1 and 4 weeks after the last PDX treatment. During the administration period, body weight loss and proprioceptive loss occurred. After the treatments were completed, electrophysiological recordings showed that the H-reflex of the treated dogs had disappeared at week 0. These phenomena persisted for four weeks exceptional body weight. CV and HE staining revealed that neurons in DRG had significant loss of large-sized neurons 0 weeks, but these neurons were recovered 4 weeks. Iba-1 and GFAP immunohistochemistry showed that reactive microgliosis and satellite glial cells were pronounced at 1 week. Conclusions: This result suggests that PDX-induced neuropathy model is reversible and can be a good experimental model for research on neuropathy in dogs.

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Morphological and electrophysiological changes in mouse dorsal root ganglia after partial colonic obstruction

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00028.2005 ◽

2005 ◽

Vol 289 (4) ◽

pp. G670-G678 ◽

Cited By ~ 36

Author(s):

Tian-Ying Huang ◽

Menachem Hanani

Keyword(s):

Glial Cells ◽

Dorsal Root Ganglia ◽

Dorsal Root ◽

Neuronal Excitability ◽

Colonic Obstruction ◽

Resting Potential ◽

Dye Coupling ◽

Drg Neurons ◽

Satellite Glial Cells ◽

Colon Wall

There is evidence that sensitization of neurons in dorsal root ganglia (DRG) may contribute to pain induced by intestinal injury. We hypothesized that obstruction-induced pain is related to changes in DRG neurons and satellite glial cells (SGCs). In this study, partial colonic obstruction was induced by ligation. The neurons projecting to the colon were traced by an injection of 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate into the colon wall. The electrophysiological properties of DRG neurons were determined using intracellular electrodes. Dye coupling was examined with an intracellular injection of Lucifer yellow (LY). Morphological changes in the colon and DRG were examined. Pain was assessed with von Frey hairs. Partial colonic obstruction caused the following changes. First, coupling between SGCs enveloping different neurons increased 18-fold when LY was injected into SGCs near neurons projecting to the colon. Second, neurons were not coupled to other neurons or SGCs. Third, the firing threshold of neurons projecting to the colon decreased by more than 40% ( P < 0.01), and the resting potential was more positive by 4–6 mV ( P < 0.05). Finally, the number of neurons displaying spontaneous spikes increased eightfold, and the number of neurons with subthreshold voltage oscillations increased over threefold. These changes are consistent with augmented neuronal excitability. The pain threshold to abdominal stimulation decreased by 70.2%. Inflammatory responses were found in the colon wall. We conclude that obstruction increased neuronal excitability, which is likely to be a major factor in the pain behavior observed. The augmented dye coupling between glial cells may contribute to the neuronal hyperexcitability.

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