Fight Aging!

There has been some research into the use of ultrasound for short-term disruption of the blood-brain barrier, to allow medication through without excessive delivery of unwanted materials into the central nervous system. In the course of this line of work, researchers observed that ultrasound treatments resulted in improved cognitive function in mice. Here, it is suggested that this has nothing to do with the blood-brain barrier effects, but instead it is in some way upregulating neurogenesis, the production of new neurons and their integration into neural circuits in memory-related areas of the brain. The present view on neurogenesis is that more of it would be a good thing, even in youth, and the decline of neurogenesis with age is an unfortunate outcome that should be prevented. Might suitable ultrasound treatments have a large enough effect to matter in humans? Perhaps; it is certainly an interesting proposal.

The idea that sound waves knocking at the skull could boost memory continues to sound far-fetched to many Alzheimer's researchers, but researchers report that scanning ultrasound improved synaptic signaling, increased neurogenesis, and sharpened spatial memory in old wild-type mice. Importantly, this worked without breaching the blood-brain barrier, a commonly used ultrasound trick to provoke a brain response. Whether this technique is appropriate for people remains to be seen, though early stage clinical trials in older adults indicate it may be safe.

Previous work had suggested ultrasound somehow opens TRPA1 calcium channels in astrocytes, which then release glutamate to activate NMDA receptors on nearby neurons. Researchers looked for signs of astrocyte-mediated activation in mouse hippocampal tissue via Western blots, and found that tissue from mice exposed to ultrasound contained more TRPA1 than tissue from control.

Evidence of NMDA activation came when the scientists separated hippocampal tissue into total and postsynaptic fractions. In the postsynaptic fraction, ultrasound had bumped up the amount of NR2B, a subunit of NMDA receptors that is needed for long-term potentiation (LTP), a form of synaptic plasticity. LTP is crucial for learning and memory and by 20 months of age, it has faded. However, the scanning ultrasound had restored LTP in aged mice, as judged by evoked potentials in hippocampal slices. Based on dentate gyrus expression of doublecortin, a marker of new neurons, the authors concluded that ultrasound upped neurogenesis 13-fold. The scientists did not track how long the memory changes lasted. "Because there are changes at the NDMA receptor level, my gut feeling is that ultrasound leads to long-lasting changes."

Link: https://www.alzforum.org/news/research-news/no-breach-needed-ultrasound-improves-memory-mice