Neurobiology of disease
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Neurobiology of disease · May 2014
White matter connectivity reflects clinical and cognitive status in Huntington's disease.
To investigate structural connectivity and the relationship between axonal microstructure and clinical, cognitive, and motor functions in premanifest (pre-HD) and symptomatic (symp-HD) Huntington's disease. ⋯ We have provided evidence of aberrant connectivity and microstructural integrity in white matter networks in HD. Microstructural changes in the cortico-striatal fibers were associated with cognitive and motor performance in pre-HD, suggesting that changes in axonal integrity provide an early marker for clinically relevant impairment in HD.
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Neurobiology of disease · May 2014
Strain- and age-dependent hippocampal neuron sodium currents correlate with epilepsy severity in Dravet syndrome mice.
Heterozygous loss-of-function SCN1A mutations cause Dravet syndrome, an epileptic encephalopathy of infancy that exhibits variable clinical severity. We utilized a heterozygous Scn1a knockout (Scn1a(+/-)) mouse model of Dravet syndrome to investigate the basis for phenotype variability. These animals exhibit strain-dependent seizure severity and survival. ⋯ Furthermore, elevated INa density in excitatory pyramidal neurons at P21-24 correlates with age-dependent onset of lethality in F1. Scn1a(+/-) mice. Our findings illustrate differences in hippocampal neurons that may underlie strain- and age-dependent phenotype severity in a Dravet syndrome mouse model, and emphasize a contribution of pyramidal neuron excitability.