What appears to happen is that the prefrontal cortex accumulates too much of the signaling molecule known as cAMP. It opens too many ion channels (the primary means of generating neuronal firing), which weakens the neurons. The researchers went to the medical chemistry shelf to look for agents that either inhibit or block cAMP sensitive ion channels and came up with guanfacine, a relatively common drug (Tenex is its proprietary name) used to treat attention deficit disorder (ADHD), anxiety attacks and sometimes high blood pressure. After applying this drug to older animals, they found that significant neuronal firing rate capacity was restored; again implying better short-term memory.

What’s significant here is not just that this is another shot at extending the length and quality of life, but that it has a reasonable scientific background AND it is moving into clinical trials (stage one). That is the significant part. If guanfacine proves to have beneficial effect on the memory of the elderly and doesn’t show any dangerous side effects or long-term problems – add it to the growing armamentarium against old age. It’s on such advances that the claim of human beings living to (at least) 150 years is made.

There is a hint of spaghetti-hitting-wall technique in this. (You know, the old “throw spaghetti against the wall and see what sticks” method of determining experimental evidence.) Or perhaps a taste of the magic elixir from the fountain of youth. But then, the search for longer, better life is probably as old as our awareness of aging and death. Sometimes solutions are found long before we know precisely why they work.

The investigators were following a hunch that the two channels might have some kind of relationship. Working in vitro (Petri dish) with rat cerebellum brain cells, they found that the A-type potassium channels, which control firing, dendritic activity, and synaptic integration, have in their channel complex calcium receptive proteins that can be activated by the T-type calcium channel. Through this link, the two channels form a signaling complex where the T-type calcium modulates the A-type channel. This is particularly important for feedback regulation of neuronal firing (one electrical system inhibits the output of another). This function is important in a wide range of electrically active cells (not just in the brain).

Principal Investigators, Ray W. Turner, Ph.D. and Gerald Zamponi, Ph.D. study the inhibitory and excitatory actions of ion channels in neurons of the cerebellum. Partnerships between the two laboratories, enabled Turner to ‘follow his hunch’ to prove that specific members of two different families of channels, previously thought to function independently, in fact function in tandem.
…
“The first results that revealed this link were amazing,” says Turner about this discovery. “These new developments redefine how we should look at the control of neuronal activity. They not only indicate how the timing of impulses from the cerebellum are controlled, but also predict how electrical activity in other parts of the brain is generated.”

[Source: EurekAlert]

While there are literally hundreds of studies based on brain scanning, showing that this or that section of the brain works with this or that brain function, there are far fewer fundamental studies such as this one. It reveals the workings of neuron cells at the molecular level, and the electrical activity at its most basic. While this is obviously a ‘small’ piece of the full story of how brain cells generate and coordinate electrical signals, it opens an important new avenue of approach – one that was not considered before.