Glucocorticoid treatment improved thinking and memory problems in a mouse model of Duchenne muscular dystrophy (DMD), pointing to a possible way to protect the brain in people living with the disease, according to a study published recently in Molecular Neurobiology.
While this work was done in mice and not humans, it suggests that commonly used steroids may help address the cognitive challenges that affect many with DMD.
Read more about the prognosis of DMD
Steroids are standard therapy for muscle symptoms, but their effects on the brain have remained unclear. In this study, researchers tested 6α-methylprednisolone, or MP, in mdx mice, a well-established model of DMD. Mice received daily injections of 1 mg/kg for five weeks.
Mdx mice that didn’t receive treatment showed clear problems with long-term memory. In a recognition test, their ability to identify a new object dropped to a score of 48.89, compared with 68.22 in healthy mice.
MP reversed this deficit, raising scores to 70.33. In a water maze used to measure spatial memory, untreated mdx mice spent much less time in the maze’s target area (41.63 seconds) compared to mice treated with MP (54.69 seconds). These improvements occurred without changes in body weight, anxiety or movement, suggesting the gains were truly cognitive.
In the brain, MP restored normal levels of several important proteins. Untreated mdx mice had reduced Dp71 and GABRA2 and elevated PSD-95, changes linked to disrupted communication between nerve cells. MP corrected all three. The drug also increased the density of dendritic spines and improved the branching structure of neurons, both essential for learning.
“Collectively, these changes promote synaptic plasticity and improve cognitive function through modulation of the excitatory/inhibitory neurotransmitter balance,” explained this study’s authors.
The team found that mdx mice showed unusually strong long-term potentiation, a form of brain activity involved in memory. MP brought this back toward normal, further supporting its role in stabilizing brain signaling.
Gene expression studies showed widespread neuroinflammation in the mdx brain. MP reduced activation of the NF-κB/CCL5 pathway and lowered levels of inflammatory molecules like TNF-α, IL-1β, IL-6 and CCL5.
These results highlight inflammation as a driver of cognitive problems in DMD. For patients, this research does not change treatment today, but it indicates that targeting inflammation in the brain might one day help protect thinking and memory.
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