IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Axonal transport is dependent on intact kinesin-1 in the important memory circuit from hippocampus to basal forebrain: A magnetic resonance imaging study
Autor/es:
MEDINA C; BIRIS O; FALZONE T; ZHANG G; JACOBS R; BEARER E
Lugar:
Chicago
Reunión:
Congreso; Annual meeting of the Society for Neuroscience; 2015
Institución organizadora:
Society for Neuroscience
Resumen:
Defects in axonal transport are implicated in peripheral neuropathies and in neurodegeneration, yet imaging transport within the living brain has proved challenging. We have developed manganese-enhanced magnetic resonance imaging (MEMRI) to witness transport within axonal bundles in living mice. In previous studies we demonstrated that Mn2+ transport is delayed in the optic nerve when kinesin-1 is defective, as occurs in the kinesin-1 light chain 1 knock-out (KLC1-KO) mice. Here we investigate whether similar transport dynamics can be detected and measured in the living brain by MEMRI. We injected 3-5 nL of 600 mM Mn2+ into CA3 of the posterior hippocampus and imaged axonal transport in vivo by capturing whole-brain 3D magnetic resonance images (MRI) at discrete time points after injection in the 11.7T Bruker scanner. Mn2+ is a paramagnetic ion that enters neurons through voltage-gated calcium channels. Once inside the neuron, Mn2+ travels down the axon apparently by axonal transport. Since Mn2=??? causes a reduction in the relaxation time of protons, a hyper-intensified signal appears in the MR image as a white contrast wherever the Mn+2??? is present. Statistical parametric mapping comparing intensities at successive time points revealed the position of the Mn2+-enhanced MR signal as it proceeded from the injection site into the forebrain, the expected projection from CA3. Comparisons of results between KLC1-KO mice to their wildtype littermates by visual inspection of statistical maps and by quantitative region of interest analyses demonstrate that distal accumulation of Mn2+-induced intensity changes is delayed by 30% at 6 hr post-injection, and achieved normal levels at 24 hr in the KLC1-KO mice, suggesting a delay in axonal transport consistent with our earlier findings in the optic tract. DTI and correlation histology showed that the KLC1-KO brain is 10% smaller with similar decrease diameter of axonal bundles, which was insufficient to account for the delayed transport. These findings demonstrate that transport in the central nervous system is in part dependent on intact kinesin-1, and that MEMRI has the power to detect differences in transport dynamics within the living brain.