Chemical reaction keeps Stroke-damaged brain from repairing itself

Stuart A. Lipton, M.D., Ph.D., is director of the Del E. Webb Neuroscience, Aging, and Stem Cell Research Center at Sanford-Burnham Medical Research Institute and a clinical neurologist. 

Credit: Sanford-Burnham Medical Research Institute.

Nitric oxide, a gaseous molecule produced in the brain, can damage neurons.

When the brain produces too much nitric oxide, it contributes to the severity and progression of stroke and neurodegenerative diseases such as Alzheimer's.

Researchers at Sanford-Burnham Medical Research Institute recently discovered that nitric oxide not only damages neurons, it also shuts down the brain's repair mechanisms.

Their study was published by the Proceedings of the National Academy of Sciences (PNAS) the week of February 4.

"In this study, we've uncovered new clues as to how natural chemical reactions in the brain can contribute to brain damage—loss of memory and cognitive function—in a number of diseases," said Stuart A. Lipton, M.D., Ph.D., director of Sanford-Burnham's Del E. Webb Neuroscience, Aging, and Stem Cell Research Center and a clinical neurologist.

Lipton led the study, along with Sanford-Burnham's Tomohiro Nakamura, Ph.D., who added that these new molecular clues are important because "we might be able to develop a new strategy for treating stroke and other disorders if we can find a way to reverse nitric oxide's effect on a particular enzyme in nerve cells."

Nitric oxide inhibits the neuroprotective ERK1/2 signaling pathway Learning and memory are in part controlled by NMDA-type glutamate receptors in the brain.

These receptors are linked to pores in the nerve cell membrane that regulate the flow of calcium and sodium in and out of the nerve cells. When these NMDA receptors get over-activated, they trigger the production of nitric oxide.

In turn, nitric oxide attaches to other proteins via a reaction called S-nitrosylation, which was first discovered by Lipton and colleagues. When those S-nitrosylated proteins are involved in cell survival and lifespan, nitric oxide can cause brain cells to die prematurely—a hallmark of neurodegenerative disease.

In their latest study, Lipton, Nakamura and colleagues used cultured neurons as well as a living mouse model of stroke to explore nitric oxide's relationship with proteins that help repair neuronal damage.

They found that nitric oxide reacts with the enzyme SHP-2 to inhibit a protective cascade of molecular events known as the ERK1/2 signaling pathway. Thus, nitric oxide not only damages neurons, it also blocks the brain's ability to self-repair.

Love, Lust and the Brain's anatomy

Helen Fisher’s pioneering work into the neural substrates of love identified three distinct yet overlapping systems for love: the hypothalamus for lust, the ventral tegmental area (VTA) for romantic love and the ventral pallidum for attachment. And in terms of confusing love and lust, she says that the two are very closely aligned, both in experience and biology.

“These brain systems often work together, but I think it’s fair to say they often don’t work together too,” Fisher told me.

“One might feel deep attachment for one partner, be in romantic love with another partner,and then be sexually attracted to many others.

There’s overlap, but like a kaleidoscope, the patterns are different.”

And that kaleidoscope can change based on experience, age or other environmental factors.

When I pressed on the lust/love question, she simply said that lust can turn into love—and vice versa (something that most of us know firsthand).

But she couldn’t offer any concrete, nitty-gritty answer about how to tell the two apart.

Love vs. Lust (and the Brain) and Helen Fisher on the neurobiology of love