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  • Low-intensity ultrasound restores long-term potentiation and memory in senescent mice through pleiotropic mechanisms including NMDAR signaling.

Low-intensity ultrasound restores long-term potentiation and memory in senescent mice through pleiotropic mechanisms including NMDAR signaling.

Molecular psychiatry (2021-05-28)
Daniel G Blackmore, Fabrice Turpin, Tishila Palliyaguru, Harrison T Evans, Antony Chicoteau, Wendy Lee, Matthew Pelekanos, Nghia Nguyen, Jae Song, Robert K P Sullivan, Pankaj Sah, Perry F Bartlett, Jürgen Götz
ABSTRACT

Advanced physiological aging is associated with impaired cognitive performance and the inability to induce long-term potentiation (LTP), an electrophysiological correlate of memory. Here, we demonstrate in the physiologically aged, senescent mouse brain that scanning ultrasound combined with microbubbles (SUS+MB), by transiently opening the blood-brain barrier, fully restores LTP induction in the dentate gyrus of the hippocampus. Intriguingly, SUS treatment without microbubbles (SUSonly), i.e., without the uptake of blood-borne factors, proved even more effective, not only restoring LTP, but also ameliorating the spatial learning deficits of the aged mice. This functional improvement is accompanied by an altered milieu of the aged hippocampus, including a lower density of perineuronal nets, increased neurogenesis, and synaptic signaling, which collectively results in improved spatial learning. We therefore conclude that therapeutic ultrasound is a non-invasive, pleiotropic modality that may enhance cognition in elderly humans.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-phospho-N-Methyl D-Aspartate NR2B Subunit (pTyr1472) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Evans Blue, Dye content ≥75 %
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Anti-Growth Associated Protein 43 Antibody, clone 9-1E12, clone 9-1E12, Chemicon®, from mouse
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Anti-Actin Antibody, clone C4, clone C4, Chemicon®, from mouse
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Anti-PSD95 Antibody, clone K28/43, clone K28/43, from mouse