Cortical and brainstem neurons containing calcium‐binding proteins in a murine model of Duchenne's muscular dystrophy: Selective changes in the sensorimotor cortex

Abstract

In the muscular dystrophic (mdx) mouse, which is characterized by deficient dystrophin expression and provides a model of Duchenne's muscular dystrophy, we previously demonstrated marked central nervous system alterations and in particular a quantitative reduction of corticospinal and rubrospinal neurons and pathologic changes of these cells. Prompted by these findings and in view of the relations between calcium ions and dystrophin, we analyzed with immunohistochemistry the neurons containing the calcium-binding proteins parvalbumin, calbindin D28k, and calretinin in cortical areas and brainstem nuclei of mdx mice. In the sensorimotor cortex, parvalbumin-positive and calbindin-positive neurons, which represent a subset of cortical interneurons, were significantly more numerous in mdx mice than in wild-type ones. In addition, the laminar distribution of parvalbumin-positive neurons in the motor and somatosensory cortical areas of mdx mice was altered with respect to wild-type animals. No alterations in the number and distribution were found in the parvalbumin- or calbindin-expressing cell populations of the visual and anterior cingulate cortices of mdx mice. The pattern of calretinin immunoreactivity was normal in all investigated cortical areas. The cell populations containing either calcium-binding protein were similar in brainstem nuclei of mdx and wild-type mice. The present findings demonstrated selective changes of subsets of interneurons in the motor and somatosensory cortical areas of mdx mice. Therefore, the data showed that, in the cortices of these mutant animals, the previously demonstrated pathologic changes of corticospinal cell populations are accompanied by marked alterations in the local circuitry.

Decreased Gray Matter Concentration and Local Synchronization of Spontaneous Activity in the Motor Cortex in Duchenne Muscular Dystrophy

“…This result was very consistent with that in the literature, 32 indicating that the deceased muscle strength is closely related to the progressive deterioration of the disease. We performed correlation analysis between muscle strength and neuroimaging indices (ReHo and GMC value).…”

Dystrophins, Utrophins, and Associated Scaffolding Complexes: Role in Mammalian Brain and Implications for Therapeutic Strategies

“…The early finding that CA1 hippocampal neurons in mdx mice are more susceptible to hypoxia-induced reduction in neurotransmission [117] suggested a critical role for dystrophin in synaptic function. Despite changes in the distribution of neuronal cells in specific cortices [118], we did not find gross histological abnormalities in brains of mdx mice [119]. Current hypotheses consider that the brain alterations are most likely located at the cellular level, and there is now ample evidence that the Dp427-DGC modulates synapse function in brain structures expressing dystrophin.…”

Acetylcholine, GABA and neuronal networks: A working hypothesis for compensations in the dystrophic brain

“…The pattern of neurons that contain calcium-binding proteins in the cortex and brainstem in mdx was later investigated via immunoreactivity to PV, calbindin (CB), or calretinin. Findings included an increase in PV-and CB-containing cells in the sensorimotor cortex (Carretta et al, 2003), which were later analyzed using Voronoi diagrams, a method to study spatial relationships between cells. The latter analysis had revealed an increase in the number of polygons for both the PV-and CB-containing populations in the sensorimotor cortex, with PV-containing population being more numerous in V layer of the motor cortex and in the IV layer of the somatosensory cortex of mdx when compared with controls (Carretta et al, 2004).…”