Progesterone Alleviates Neural Behavioral Deficits and Demyelination with Reduced Degeneration of Oligodendroglial Cells in Cuprizone-Induced Mice

Abstract

Demyelination occurs widely in neurodegenerative diseases. Progesterone has neuroprotective effects, is known to reduce the clinical scores and the inflammatory response. Progesterone also promotes remyelination in experimental autoimmune encephalomyelitis and cuprizone-induced demyelinating brain. However, it still remains unclear whether progesterone can alleviate neural behavioral deficits and demyelination with degeneration of oligodendroglial cells in cuprizone-induced mice. In this study, mice were fed with 0.2% cuprizone to induce demyelination, and treated with progesterone to test its potential protective effect on neural behavioral deficits, demyelination and degeneration of oligodendroglial cells. Our results showed noticeable alleviation of neural behavioral deficits following progesterone treatment as assessed by changes in average body weight, and activity during the open field and Rota-rod tests when compared with the vehicle treated cuprizone group. Progesterone treatment alleviated demyelination as shown by Luxol fast blue staining, MBP immunohistochemical staining, and electron microscopy. There was an obvious decrease in TUNEL and Caspase-3-positive apoptotic cells, and an increase in the number of oligodendroglial cells staining positive for PDGFRα, Olig2, Sox10 and CC-1 antibody in the brains of cuprizone-induced mice after progesterone administration. These results indicate that progesterone can alleviate neural behavioral deficits and demyelination against oligodendroglial cell degeneration in cuprizone-induced mice.

Oligodendrocyte Progenitor Cells Directly Utilize Lactate for Promoting Cell Cycling and Differentiation

“…C and D). Although nuclear SOX10‐positive cells were reduced after cuprizone treatment, as previously reported (Ye et al, ), DAB did not affect the nuclear SOX10‐positive cell count (Fig. E and F).…”

Therapeutic inhibition of soluble brain TNF promotes remyelination by increasing myelin phagocytosis by microglia

“…Mice were tested for overall balance, motor coordination, and motor learning using a rotarod apparatus (ENV-575M, Med Associates Inc.), as described (40). Briefly, mice were placed on the rotating cylinder at an accelerating speed of 4-40 rpm and trained for 3 sessions per day for 3 consecutive days (days 11, 12, and 13 of CPZ feeding), prior to the first test on day 14 (CPZ2), and tested once weekly from then on.…”

“…To test whether improved remyelination in XPro1595-treated mice was accompanied by better motor performance, we tested mice for overall balance, motor coordination, and motor learning using a rotarod apparatus following procedures described elsewhere (40). Motor function was reduced in vehicle-treated mice at CPZ5, as measured by marked reduction in time spent on the rotating cylinder, compared with naive mice (Figure 6).…”

Neurosteroidogenesis and progesterone anti‐inflammatory/neuroprotective effects

“…In cuprizone-intoxicated mice, progesterone given for 2 weeks alleviates demyelination, decreases apoptosis and increases markers of oligodendrogenesis. 13 In the study by El-Etr et al, 14 progesterone or the synthetic progestin Nestorone delivered s.c. from implanted minipums increases myelin formation in corpus callosum and cerebral cortex, as well as the number of mature oligodendrocytes and their progenitors. Therefore, these latter studies suggest that progesterone also plays a therapeutic role in rodents with EAE and in cuprizone-induced demyelination.…”