Dystrophin and utrophin isoforms are expressed in glia, but not neurons, of the avian parasympathetic ciliary ganglion

Abstract

Muscular dystrophy patients often show cognitive impairment, in addition to muscle degeneration caused by dystrophin gene defects. The cognitive impairments lead to speculation that the dystrophin protein family may play a key role at neuronal synapses. Dystrophin regulates the stability of selected GABA A receptor subtypes and α3-containing nicotinic acetylcholine receptors (nAChRs) at a subset of central GABAergic and peripheral sympathetic nicotinic neuron synapses. Similarly, utrophin, the autosomal homologue of dystrophin, is not required for clustering but indirectly stabilizes muscletype nAChRs at the neuromuscular junction. We examined dystrophin and utrophin expression and localization in the avian parasympathetic ciliary ganglion (CG) to determine whether these proteins play a general role at neuronal nicotinic synapses. We have determined that full-length utrophin and dystrophin and the short dystrophin isoform Dp116 are the major isoforms expressed in the CG based on immunoblotting and immunolabeling. Unexpectedly, the cytoskeletal proteins were not detected at nicotinic synapses or in CG neurons. They are expressed in myelinating and non-myelinating Schwann cells. Further, utrophin expression developmentally precedes that of dystrophin. The proteins show partially overlapping distributions, but also differential accumulation along the surface membrane of Schwann cells adjacent to neuronal somata versus axonal processes. Our findings are consistent with reports that dystrophin protein family members function in the maintenance of cellcell interactions and myelination by anchoring the Schwann cell surface membrane to the basal lamina. In contrast, our results differ from those in skeletal muscle and a subset of sympathetic neurons where utrophin and dystrophin localize at nicotinic synapses.

Dystrophin Dp116: A yet to Be Investigated Product of the Duchenne Muscular Dystrophy Gene

“…The expression of Dp116 was assessed in the peripheral nerves and spinal cord of monkeys [15], and in glia, but not neurons, of the avian parasympathetic ciliary ganglion [16]. In rat sciatic nerve, Dp116 was expressed in a thin rim surrounding each Schwann cell-axon unit [17], whereas, in rabbit sciatic nerve, Dp116 was found to co-localize with β-dystroglycan in the sheath around each separate Schwann cell-axon unit [18,19].…”

The role of cell transplantation in modifying the course of limb girdle muscular dystrophy: a longitudinal 5-year study

“…They were characterized by low densities of synaptic vesicles at the nerve endings and other related findings. 26 – 28 Thus, intrathecal route was the choice, as it is the closest environment to the nervous system. Intramuscular injections are administered at the motor points plotted bilaterally on muscles by physiotherapists experienced in the field.…”

Autologous bone marrow mononuclear cell transplantation in Duchenne muscular dystrophy

“…Although primarily a muscle disease, involvement of neural structures has been observed. Dystrophin has been thought to play a role in the neuronal synapses and myelination of the nerves by anchoring the Schwann cells [ 20 , 21 ]. Nervous system impairment is manifested as impaired cognition in some children with DMD [ 22 ].…”