Reduced neuronal density in the CA1 anterodorsal hippocampus of the mdx mouse.
Duchenne muscular dystrophy (DMD) is associated with non-progressive cognitive dysfunction including hippocampal-dependent memory deficits. Loss of the cytoskeleton-associated dystrophin protein in central inhibitory synapses, associated with consequent alterations in GABAergic function and synaptic plasticity, has been proposed as a primary mechanism responsible for cognitive impairments. However, several lines of evidence suggest a multifactorial etiology involving alternative signaling pathways, some of which could affect neuronal survival. To determine whether changes in neuronal density in the hippocampus could contribute to the emergence of memory deficits, we undertook an unbiased stereological estimation of neuron number in the anterodorsal CA1 region of the hippocampus of the dystrophin-deficient mdx mouse model of DMD. We found a significant reduction (~34%) in the number of pyramidal neurons, with a heterogeneous magnitude of genotype differences along the hippocampal antero-posterior axis. This extends previous knowledge of brain morphofunctional alterations induced by dystrophin loss and suggests that putative mechanisms involved in neurogenesis and/or neuron survival might contribute to the emergence of hippocampal-dependent learning and memory deficits in DMD.
Neuroscience Paris-Saclay Institute (Neuro-PSI), UMR 9197, Université Paris Sud, CNRS, Université Paris Saclay, Orsay, France. Electronic address: ruben.miranda@pdi.ucm.es.
Rubén
R
Miranda
Neuroscience Paris-Saclay Institute (Neuro-PSI), UMR 9197, Université Paris Sud, CNRS, Université Paris Saclay, Orsay, France.
Serge
S
Laroche
Neuroscience Paris-Saclay Institute (Neuro-PSI), UMR 9197, Université Paris Sud, CNRS, Université Paris Saclay, Orsay, France.
Cyrille
C
Vaillend
D000818:Animals; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D002452:Cell Count; D004195:Disease Models, Animal; D008297:Male; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000473:pathology*; D017966:Pyramidal Cells / Q000473:pathology*
Duchenne muscular dystrophy; Dystrophin; Hippocampus; Neuronal density; mdx mice