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Learning deficits in aged rats related to decrease in extracellular volume and loss of diffusion anisotropy in hippocampus.
E. Sykova, T. Mazel, R.U. Hasenöhrl, A.R. Harvey, Z. Simonova, W.H.A.M. Mulders, J.P. Huston
Institute of Physiological Psychology and Center for Biological and Medical Research, University of Düsseldorf, Düsseldorf, Germany
The extracellular space (ECS) is the microenvironment of the nerve cells
and an important communication channel, Acta Radiol allowing for long-distance
extrasynaptic communication between cells. Changes in ECS size, geometry,
and composition have been reported in diverse (patho)physiological states,
including aging. In the present study, real-time tetramethylammonium (TMA+)
iontophoresis was used to quantify ECS diffusion parameters in different
brain regions of adult and behaviorally characterized aged rats. Prior
to ECS diffusion measurement, superior and inferior learners were selected
from a large group of aged rats, according to their performance in the
open-field water maze. The main finding was that the degree of impaired
maze performance of old rats correlates, firstly, with decrease in ECS
volume, loss of diffusion anisotropy in hippocampus, and degree of astrogliosis,
and secondly, with disorganization of the astrocytic processes and reduction
of hippocampal ECS matrix molecules. Importantly, no significant differences
were found in the density of neurons in any region of the hippocampus or
dentate gyrus. The alterations in hippocampal diffusion parameters evident
in aged animals with severe learning deficits could account for the learning
impairment, due to their effects on extrasynaptic volume transmission and/or
on the cross-talk between synapses, which has been suggested to be involved
in neural processes associated with learning and memory formation.
