Altered presynaptic ultrastructure in excitatory hippocampal synapses of mice lacking dystrophins Dp427 or Dp71

• Published in: Neurobiology of disease 2011-07, Vol.43 (1), p.134-141
• Main Authors: Miranda, Rubén, Nudel, Uri, Laroche, Serge, Vaillend, Cyrille
• Format: Article
• Language: English
• Subjects: Animals; Cognition Disorders - etiology; Cognition Disorders - genetics; Cognition Disorders - pathology; Disease Models, Animal; Drosophila; Dysbindin; Dystrophin - genetics; Dystrophin - physiology; Glutamic Acid - physiology; Hippocampus - pathology; Hippocampus - physiopathology; Hippocampus - ultrastructure; Life Sciences; Male; mdx mice; Mice; Mice, Inbred C57BL; Mice, Inbred mdx; Muscular Dystrophy, Duchenne - complications; Muscular Dystrophy, Duchenne - genetics; Muscular Dystrophy, Duchenne - pathology; Neuroligin–neurexin complex; Neurology; Neuronal Plasticity - genetics; Neurons and Cognition; Neurotransmitter release; Presynaptic Terminals - pathology; Presynaptic Terminals - ultrastructure; Protein Isoforms - genetics; Protein Isoforms - ultrastructure; Synaptic plasticity; Synaptic vesicle cycling; Synaptic Vesicles - genetics; Synaptic Vesicles - pathology; Synaptic Vesicles - ultrastructure
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2011.02.017

Abstract Mental retardation is a feature of X-linked Duchenne muscular dystrophy (DMD) which likely results from the loss of the brain full-length (Dp427) and short C-terminal products of the dystrophin gene, such as Dp71. The loss of Dp427 or Dp71 is known to alter hippocampal glutamate-dependent synaptic transmission and plasticity in mice. Although dystrophins have a selective postsynaptic expression in brain, a putative role in retrograde regulation of transmitter release was suggested by studies in Drosophila. Here we used electron microscopy to analyze the distribution of synaptic vesicles in CA1 hippocampal axospinous non perforated-excitatory synapses of mice lacking Dp427 or Dp71 compared to control littermates. We found that the density of morphologically-docked vesicles is increased and the vesicle size is reduced in mice lacking Dp427, while in Dp71-null mice there is a decrease in the density of vesicles located in the vicinity of the active zone and an increase in the vesicle size and in the width of synaptic clefts. This is the first indication that the loss of mammalian brain dystrophins impacts on the presynaptic ultrastructural organization of central glutamatergic synapses, which may explain some of the alterations of synapse function and plasticity that contribute to intellectual disability in DMD.