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Updated: Jun 3, 2026
Evaluation of Synapse Density in Hippocampal Rodent Brain Slices
Published on: October 6, 2017
Altered presynaptic ultrastructure in excitatory hippocampal synapses of mice lacking dystrophins Dp427 or Dp71
Rubén Miranda1, Uri Nudel, Serge Laroche
1Univ Paris-Sud, Centre de Neurosciences Paris-Sud, UMR 8195, Orsay F-91405, France. ruben.miranda@pdi.ucm.es
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.
Insights
Intellectual disability in Duchenne muscular dystrophy (DMD) may stem from altered brain dystrophin. Loss of Dp427 or Dp71 impacts synaptic vesicle organization in the mouse hippocampus.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- Intellectual disability is a known feature of Duchenne muscular dystrophy (DMD).
- This cognitive impairment is linked to the loss of brain dystrophin isoforms, specifically Dp427 and Dp71.
- Previous studies in mice showed that loss of these dystrophins affects hippocampal synaptic function and plasticity.
Purpose of the Study:
- To investigate the presynaptic ultrastructural organization of central glutamatergic synapses in mice lacking Dp427 or Dp71.
- To determine if the absence of brain dystrophin isoforms impacts synaptic vesicle distribution and morphology.
Main Methods:
- Electron microscopy was employed to examine CA1 hippocampal axospinous excitatory synapses in mice.
- Analysis focused on comparing synaptic vesicle density, size, and synaptic cleft width in control littermates versus mice lacking Dp427 or Dp71.
Main Results:
- Mice lacking Dp427 showed an increased density of docked vesicles and reduced vesicle size.
- Mice lacking Dp71 exhibited decreased vesicle density near the active zone, increased vesicle size, and wider synaptic clefts.
- These findings represent the first evidence of altered presynaptic ultrastructure in mammalian brain synapses due to dystrophin loss.
Conclusions:
- The loss of mammalian brain dystrophins, Dp427 and Dp71, significantly impacts the presynaptic organization of glutamatergic synapses.
- These ultrastructural changes in synaptic vesicles and clefts may underlie the synaptic dysfunction and plasticity alterations contributing to intellectual disability in DMD.
