Essential role of hippocampal noradrenaline in the regulation of spatial working memory and TDP‐43 tissue pathology

Essential role of hippocampal noradrenaline in the regulation of spatial working memory and... Extensive loss of noradrenaline‐containing neurons and fibers is a nearly invariant feature of Alzheimer's Disease (AD). However, the exact noradrenergic contribution to cognitive and histopathological changes in AD is still unclear. Here, this issue was addressed following selective lesioning and intrahippocampal implantation of embryonic noradrenergic progenitors in developing rats. Starting from about 3 months and up to 12 months post‐surgery, animals underwent behavioral tests to evaluate sensory‐motor, as well as spatial learning and memory, followed by post‐mortem morphometric analyses. At 9 months, Control, Lesioned and Lesion + Transplant animals exhibited equally efficient sensory‐motor and reference memory performance. Interestingly, working memory abilities were seen severely impaired in Lesion‐only rats and fully recovered in Transplanted rats, and appeared partly lost again 2 months after ablation of the implanted neuroblasts. Morphological analyses confirmed the almost total lesion‐induced noradrenergic neuronal and terminal fiber loss, the near‐normal reinnervation of the hippocampus promoted by the transplants, and its complete removal by the second lesion. Notably, the noradrenergic‐rich transplants normalized also the nuclear expression of the transactive response DNA‐binding protein 43 (TDP‐43) in various hippocampal subregions, whose cytoplasmic (i.e., pathological) occurrence appeared dramatically increased as a result of the lesions. Thus, integrity of ascending noradrenergic inputs to the hippocampus may be required for the regulation of specific aspects of learning and memory and to prevent TDP‐43 tissue pathology. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Comparative Neurology Wiley

Essential role of hippocampal noradrenaline in the regulation of spatial working memory and TDP‐43 tissue pathology

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Publisher
Wiley
Copyright
© 2018 Wiley Periodicals, Inc.
ISSN
0021-9967
eISSN
1096-9861
D.O.I.
10.1002/cne.24397
Publisher site
See Article on Publisher Site

Abstract

Extensive loss of noradrenaline‐containing neurons and fibers is a nearly invariant feature of Alzheimer's Disease (AD). However, the exact noradrenergic contribution to cognitive and histopathological changes in AD is still unclear. Here, this issue was addressed following selective lesioning and intrahippocampal implantation of embryonic noradrenergic progenitors in developing rats. Starting from about 3 months and up to 12 months post‐surgery, animals underwent behavioral tests to evaluate sensory‐motor, as well as spatial learning and memory, followed by post‐mortem morphometric analyses. At 9 months, Control, Lesioned and Lesion + Transplant animals exhibited equally efficient sensory‐motor and reference memory performance. Interestingly, working memory abilities were seen severely impaired in Lesion‐only rats and fully recovered in Transplanted rats, and appeared partly lost again 2 months after ablation of the implanted neuroblasts. Morphological analyses confirmed the almost total lesion‐induced noradrenergic neuronal and terminal fiber loss, the near‐normal reinnervation of the hippocampus promoted by the transplants, and its complete removal by the second lesion. Notably, the noradrenergic‐rich transplants normalized also the nuclear expression of the transactive response DNA‐binding protein 43 (TDP‐43) in various hippocampal subregions, whose cytoplasmic (i.e., pathological) occurrence appeared dramatically increased as a result of the lesions. Thus, integrity of ascending noradrenergic inputs to the hippocampus may be required for the regulation of specific aspects of learning and memory and to prevent TDP‐43 tissue pathology.

Journal

The Journal of Comparative NeurologyWiley

Published: Jan 1, 2018

Keywords: ; ; ; ; ; ; ; ;

References

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