High-dose levodopa-associated peripheral neuropathy and glial alterations in stressed mice: Protective effects of Vitamin B12

Although L-DOPA is the primary treatment for motor symptoms of PD, chronic high-dose exposure may contribute to PN. Using stressed but otherwise healthy mice, we found that high-dose L-DOPA increased cold and tactile sensitivity, reduced heat nociception, and reduced cutaneous small nerve fibers, consistent with PN.

Vitamin B12 partially rescued deficits in noxious temperature sensation. L-DOPA also reduced lysosomal markers in the gut, altered oligodendrocyte lineage dynamics, and increased microglial activation in the spinal cord. In substantia nigra, L-DOPA-induced astrocytosis was attenuated by Vitamin B12.