ABSTRACT
Lack of dystrophin is known to reduce several cerebral fiber systems. To investigate if the loss of fibers is progressive, we analyzed projections of the trigeminal sensory system to the red nucleus in 3, 6, and 12 month old dystrophin-deficient mdx mice. The retrograde tracer fluorogold was injected in the magnocellular part of the red nucleus, and the number of labeled neurons in the oral part of the spinal trigeminal nucleus (Sp5O) was counted. We found that the number of labeled Sp5O neurons was reduced by 50% in mdx mice compared to age-matched control mice. The number of labeled Sp5O neurons did not change significantly between 3 and 12 months neither in mdx nor in control mice. In addition, the number of labeled neurons in the interstitial system of the trigeminal nerve was reduced by 43% in mdx mice. We conclude that fiber loss did not continue beyond the age of 3 months. Our data suggest that lack of full-length dystrophin impairs neuronal migration or axonal outgrowth, or increases neuronal death during fetal or early life.
Subject(s)
Axons/metabolism , Dystrophin/genetics , Nerve Degeneration/metabolism , Red Nucleus/abnormalities , Trigeminal Nucleus, Spinal/abnormalities , Animals , Axons/ultrastructure , Brain Mapping , Cell Count , Cell Death/genetics , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL , Mice, Inbred mdx , Nerve Degeneration/genetics , Nerve Degeneration/physiopathology , Nervous System Malformations/genetics , Nervous System Malformations/metabolism , Nervous System Malformations/physiopathology , Neural Pathways/abnormalities , Neural Pathways/cytology , Neural Pathways/metabolism , Red Nucleus/cytology , Red Nucleus/metabolism , Stilbamidines , Trigeminal Nerve/abnormalities , Trigeminal Nerve/cytology , Trigeminal Nerve/metabolism , Trigeminal Nucleus, Spinal/cytology , Trigeminal Nucleus, Spinal/metabolism , Wallerian Degeneration/genetics , Wallerian Degeneration/metabolism , Wallerian Degeneration/physiopathologyABSTRACT
The lack of dystrophin that causes Duchenne muscle disease affects not only the muscles but also the central nervous system. Dystrophin-deficient mdx mice present changes in several brain fiber systems. We compared the projections from the trigeminal sensory nuclear complex to the red nucleus in control and mdx mice using retrograde tracers. Injection of 200 nL 2% fluorogold into the red nucleus caused labeling in the mesencephalic trigeminal nucleus, the principal sensory nucleus and the oral, interpolar, and caudal subnuclei of the spinal trigeminal nucleus in both control and mdx mice. Injection of latex microbeads labeled with rhodamine and fluorescein gave results similar to those seen with fluorogold. The number of labeled neurons in the trigeminal sensory nuclear complex was significantly reduced in mdx mice. In the oral subnucleus of the spinal trigeminal nucleus this reduction was 50%. These results indicate that the trigemino-rubral pathway is reduced in dystrophin-deficient mice.
