Christian Viel

Background: Peripheral neuropathy (PN) is one of the most common disorders of the peripheral nervous system, affecting around 10% of the general adult population. PN results in pain, paraesthesia, and sensory loss, negatively impacting patients’ quality of life. The condition is characterised by damage to peripheral nerves and is often linked to risk factors, among which diabetes is the most common cause. The incidence rate of patients suffering from PN has significantly increased in the last three decades, yet there are currently no pharmacological treatments to reverse or prevent the development of PN. Therefore, neurotropic B vitamins, specifically vitamins B1, B6, and B12, which are essential for protecting nerves from damage, nerve regeneration, and maintaining nerve health, are promising treatment options. Other biofactors with therapeutic potential are vitamin D3, which has been described as a regulator of neuroplasticity and neuroinflammation with indications to promote neuronal regeneration following injury, as well as alpha-lipoic acid (ALA), a well-described treatment option in PN. Methods: The regenerative capacity of vitamins B1, B6, B12, and D3 and ALA was determined following neurite degeneration in vitro induced by either hydrogen peroxide (H₂O₂) or homocysteine. Results: In line with previous studies, the results show that a combination of vitamins B1, B6, and B12 has a significantly better effect on neurite extension following homocysteine-induced degeneration. In H₂O₂-insulted neural cells, the combination of all three neurotropic B vitamins was also shown to be superior to that of individual B vitamin treatment, demonstrated by longer neurite length after insult. Vitamin D3 also demonstrated a neuro-regenerative effect on neurites in healthy and insulted neural cells, whereas ALA only appears to provide a protective effect, preventing ongoing damage and supporting neurite outgrowth in healthy cells. No synergistic effects were seen with any treatment combinations. Conclusions: We have established an in vitro model of homocysteine-induced degeneration, and using this model alongside H₂O₂-induced degeneration, we provide evidence of the neurite regenerative capacity of vitamins B1, B6, B12, and D3.

Peripheral neuropathy (PN) is a prevalent condition characterized by damage to peripheral nerves, often linked to risk factors such as diabetes. This condition results from various forms of neural damage, including injury to the cell body, axons, or demyelination, frequently beginning with small and thinly or unmyelinated fibers. Such nerve damage disrupts normal signaling, leading to symptoms like numbness, tingling, and pain. Effective nerve repair and regeneration, particularly through remyelination, are essential therapeutic objectives. While vitamin B12’s role in repair processes has been well established, emerging evidence suggests that other neurotropic vitamins, specifically B1 and B6, also contribute significantly to nerve health and symptom relief in PN. In this study, we demonstrate that a combination treatment of vitamins B1, B6, and B12 enhances repair and oxidative stress responses in co-cultures of neural and Schwann cells, leading to improved cell maturation and connectivity compared to vitamin B12 alone. Furthermore, proteomic analysis supports these observations at the molecular level, with enhanced cellular recycling processes like proteasome enhancement, as well as protein synthesis upregulation, needed to rebuild nerve connections and combatting oxidative stress. Our combined morphological and molecular results highlight the potential therapeutic advantage of the B1, B6, and B12 combination over vitamin B12 alone.

Antioxidants have been proposed as a treatment for diseases of the central nervous system. However, few studies actually studied their effects in the brain. To test central actions of antioxidants, we used the lithium–pilocarpine (Li-Pilo) model of status epilepticus (SE) in the rat in which seizures are accompanied by significant oxidative stress. We used in vivo microdialysis to determine isoprostane levels during SE in real time and brain homogenates for other measures of oxidative stress. Six different antioxidants were tested in acute and preventive experiments (vitamin C, vitamin E, ebselen, resveratrol, n-tert-butyl-α-phenylnitrone and coenzyme Q10). None of the antioxidants had an effect when given acutely during SE. In contrast, when antioxidants were given for 3 days prior to seizure induction, vitamins C and E reduced isoprostane formation by 58% and 65%, respectively. Pretreatment with the other antioxidants was ineffective. In brain homogenates prepared after 90 min of seizures, SE decreased the ratio of reduced vs. oxidized glutathione (GSH/GSSG ratio) from 60.8 to 7.50 and caused a twofold increase of 8-hydroxy-2′-deoxyguanosine (8-OHdG) levels and protein carbonyls. Pretreatment with vitamin C or vitamin E mitigated these effects and increased the GSH/GSSG ratio to 23.9 and 28.3, respectively. Again, the other antioxidants were not effective. We conclude that preventive treatment with vitamin C or vitamin E ameliorates seizure-induced oxidative damage in the brain. Several well-studied antioxidants were inactive, possibly due to limited brain permeability or a lack of chain-breaking antioxidant activity in hydrophilic compounds.

Glucose hypometabolism, mitochondrial dysfunction, and cholinergic deficits have been reported in early stages of Alzheimer’s disease (AD). Here, we examine these parameters in TgF344-AD rats, an Alzheimer model that carries amyloid precursor protein and presenilin-1 mutations, and of wild type F344 rats. In mitochondria isolated from rat hippocampi, we found reductions of complex I and oxidative phosphorylation in transgenic rats. Further impairments, also of complex II, were observed in aged (wild-type and transgenic) rats. Treatment with a “cocktail” containing magnesium orotate, benfotiamine, folic acid, cyanocobalamin, and cholecalciferol did not affect mitochondrial activities in wild-type rats but restored diminished activities in transgenic rats to wild-type levels. Glucose, lactate, and pyruvate levels were unchanged by age, genetic background, or treatment. Using microdialysis, we also investigated extracellular concentrations of acetylcholine that were strongly reduced in transgenic animals. Again, ACh levels in wild-type rats did not change upon treatment with nutrients, whereas the cocktail increased hippocampal acetylcholine levels under physiological stimulation. We conclude that TgF344-AD rats display a distinct mitochondrial and cholinergic dysfunction not unlike the findings in patients suffering from AD. This dysfunction can be partially corrected by the application of the “cocktail” which is particularly active in aged rats. We suggest that the TgF344-AD rat is a promising model to further investigate mitochondrial and cholinergic dysfunction and potential treatment approaches for AD.