Affiliations: [a] Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL, USA | [b] Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA | Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA
Correspondence:
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Corresponding author: Inga Kadish, Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Tel.: +1 205 934 5940; Fax: +1 205 934 7029; E-mail: ikadisha@uab.edu.
Abstract: We have studied entorhinal cortex lesion-induced sprouting in the hippocampus in young, adult, and aged control and transgenic Alzheimer's disease model mice. The entorhinal cortex was unilaterally, partially lesioned, and four weeks later the subsequent axonal sprouting in dentate gyrus was analyzed. Our data demonstrate that young and adult, control and amyloid-β protein precursor (AβPP)/presenilin 1 (PS1) mice display a significantly increased density of staining for synaptophysin in dentate gyrus, indicative of axonal sprouting. However, whereas young and adult mice demonstrate sprouting, aged mice (control and AβPP/PS1) do not show a significant upregulation of synaptophysin staining following the lesions. In contrast, aged mice overexpressing PS1 show an increased regenerative response compared to age-matched control mice and mice overexpressing AβPP which do not show sprouting. Further, the data demonstrate that a significant Aβ load in the dentate gyrus does not prevent axonal sprouting. Lastly, only aged mice show significant shrinkage of the molecular layer of dentate gyrus following entorhinal cortex lesions. Further, adult ovariectomized females (control and AβPP/PS1) are significantly reduced in their plasticity following lesions. Taken together, the data indicate that amyloid-β deposits do not negatively impact plasticity in the brain and that overexpression of AβPP is not beneficial, but that normal estrogen levels are beneficial for plasticity.
Keywords: Entorhinal cortex, hippocampus, mouse, plasticity, sex and gene differences, sprouting
