Propionate exerts neuroprotective and neuroregenerative effects in the peripheral nervous system

Abstract

In inflammatory neuropathies, oxidative stress results in neuronal and Schwann cell (SC) death promoting early neurodegeneration and clinical disability. Treatment with the short-chain fatty acid propionate showed a significant immunoregulatory and neuroprotective effect in multiple sclerosis patients. Similar effects have been described for patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Therefore, Schwann cell’s survival and dorsal root ganglia (DRG) outgrowth were evaluated in vitro after propionate treatment and application of H2O2 or S-nitroso-N-acetyl-D-L-penicillamine (SNAP) to evaluate neuroprotection. In addition, DRG resistance was evaluated by the application of oxidative stress by SNAP ex vivo after in vivo propionate treatment. Propionate treatment secondary to SNAP application on DRG served as a neuroregeneration model. Histone acetylation as well as expression of the free fatty acid receptor (FFAR) 2 and 3, histone deacetylases, neuroregeneration markers, and antioxidative mediators were investigated. β-hydroxybutyrate was used as a second FFAR3 ligand, and pertussis toxin was used as an FFAR3 antagonist. FFAR3, but not FFAR2, expression was evident on SC and DRG. Propionate-mediated activation of FFAR3 and histone 3 hyperacetylation resulted in increased catalase expression and increased resistance to oxidative stress. In addition, propionate treatment resulted in enhanced neuroregeneration with concomitant growth-associated protein 43 expression. We were able to demonstrate an antioxidative and neuroregenerative effect of propionate on SC and DRG mediated by FFAR3-induced histone acetylases expression. Our results describe a pathway to achieve neuroprotection/neuroregeneration relevant for patients with immune-mediated neuropathies.

Serum neurofilament light chain does not detect self‐reported treatment‐related fluctuations in chronic inflammatory demyelinating polyneuropathy

“…Our results suggest that more attention needs to be paid to the progression of CIDP. Also, further studies are needed to show whether these patients benefit from intensified immunotherapy or potential neuroprotective substances [19] to achieve long‐term stability.…”

Butyrate-producing bacteria as probiotic supplement: beneficial effects on metabolism and modulation of behavior in an obesity mouse model

“…In fact, the YCFAGSC medium used for culturing the four bacteria is rich in vitamins (Duncan et al, 2002) that might promote brain health (Kennedy, 2016), and became a major confounder within our study design. Notably, the culture medium was also rich in the SCFA propionate (see figure 8), which has been recently suggested to exert neuroprotective effects (e.g., Filippone et al, 2020;Hou et al, 2021;Grüter et al, 2023).…”

“…Notably, the culture medium was also rich in the SCFA propionate (see figure 8), which has been recently suggested to exert neuroprotective effects ( e.g. , Filippone et al ., 2020; Hou et al ., 2021; Grüter et al ., 2023).…”

Short chain fatty acids: the messengers from down below

“…Data published suggest that microbiome transplantation from lean to obese mice may alleviate pain and increases nerve survival and/or growth via short chain fatty acids (e.g., butyrate) (Bonomo et al, 2020). Recently, in-vitro studies demonstrated a potential antioxidative and neurodegenerative effect of propionate in the peripheral nerve system suggesting that propionate could be used in immune-mediated neuropathies (Grüter et al, 2023). Some SCFA have been demonstrated to cross the blood brain barrier in rats (Oldendorf, 1973) and in humans (Bachmann et al, 1979), possibly due to high expression of their transporter, monocarboxylate transporters (MCTs) in blood cells and astrocytes (Bachmann et al, 1979;Dalile et al, 2019).…”