Neuropathological changes in dorsal root ganglia induced by pyridoxine in dogs

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.

Circulating neurofilament light chain as a promising biomarker of AAV-induced dorsal root ganglia toxicity in nonclinical toxicology species

“…Proteins commonly used to evaluate cell-and structure-specific neurotoxicity via immunohistochemistry were identified as candidate biomarkers for DRG toxicity. This included: i) UCH-L1 for neurons (Wilson et al, 1988), ii) Tau and NF-L for axons (Kanaan and Grabinski, 2021;Mages et al, 2018), iii) microtubule-associated protein 2 (MAP2) for neuron dendrites (Gumy et al, 2017), iv) GFAP for astrocytes (Yun et al, 2020), v) 2',3'-cyclic-nucleotide 3'phosphodiesterase (CNPase) for oligodendrocytes (Toma et al, 2007), and vi) ionized calcium binding adaptor molecule 1 (IBA1) for microglia (CNS) and macrophages (PNS) (Yun et al, 2020).…”

Phenotypical peculiarities and species‐specific differences of canine and murine satellite glial cells of spinal ganglia

“…Overall, SGCs appear to be a plastic cell population with multiple functional roles. Although the interest in this cell population is growing, few studies have specifically dealt with canine SGCs (cSGCs), and current knowledge of cSGCs is scarce in comparison to murine (mSGCs) and rat SGCs 23‐25 . The dog is of particular interest as it represents a suitable translational large animal model for certain canine and human CNS diseases, including spinal cord injury.…”

“…Although the interest in this cell population is growing, few studies have specifically dealt with canine SGCs (cSGCs), and current knowledge of cSGCs is scarce in comparison to murine (mSGCs) and rat SGCs. [23][24][25] The dog is of particular interest as it represents a suitable translational large animal model for certain canine and human CNS diseases, including spinal cord injury. Dogs show comparable pathogenic mechanisms, lesion distribution and morphology as well as clinical manifestations.…”