Lonely older man (732 x 654 px)

Seriously, did you hear about the two guys bragging about their incredible memories despite their advanced age?

“I can remember every baseball statistic of the last decade”

“Big deal, I can remember every meal we ate at a restaurant in the last 10 years. By the way, last night we went to a fantastic restaurant ”

“Really? What’s its name”?

“It’s called…it’s called… What do you call the colorful flower that has this great fragrance”?

“You mean a rose”?

“Ah, yea. Hey Rose, what’s the name of the restaurant we went to last night”?

Well, this guy probably had incipient dementia. But most normal adults suffer from a certain degree of memory loss as they age. Nothing abnormal, just part of getting old.

 

What’s happening to our brain as we age?

In a word (or two): we lose neurons. During the normal maturation of the brain, we lose neurons almost from birth. This initial loss, lasting to the age of puberty, is actually very healthy. We are born with a great excess of neurons, and by dropping a large number of them the brain becomes better at filtering out extraneous “noise” and more efficient at transmitting and storing information. You have heard it said that the child and adolescent brain “is different”; less judgment, sometimes weird reasoning, and predilection for risky behavior. Part of the problem is that lack of well-defined brain structures which results from the surfeit of neurons. One theory of childhood autism is that the process of neuronal loss is somehow defective in these children, resulting in an inability to filter out the huge amount of external stimuli bombarding the brain. Hence their withdrawal from interaction with people.

Alas, once the sculpting of the brain attains its ultimate beauty, the “sculptor” does not call it quits. We continue losing neurons. Most of these losses are without much consequence because they are not noticeable in daily life. We may have trouble learning a new language, or solving a mathematical problem; so who cares? But of a more daily consequence is that as we lose hair cells in the inner ear (these cells are neuronal), we start losing our auditory acuity. First go the high-frequency sounds, and our ability to discriminate between certain consonants. Later on, we become prime targets of hearing aids ads.

The most disconcerting to most adults is the loss of memory through loss of neurons in the hippocampus, this sea-horse shaped brain structure, where different types of memory (visual, auditory) are integrated. The memory losses can be of varying severities—from the occasional forgetfulness (where did I leave my car keys?) to forgetting one’s wife name, if only for a split second.

Such loss of memory can be recreated in rats by disrupting the generation of new neurons in the hippocampus. But even more interesting, memory could be restored by allowing stem cells to generate new neurons. But rats are not human (although the opposite is not always true), and human memories are probably a much more complex affair than the rats. So the nagging question always lingered—can human memory be restored by neuronal stem cells?

In the latest online edition of the journal Brain scientists from the University of Florida tried to answer the question. The UF researchers, in collaboration with colleagues in Germany, studied 23 patients who had epilepsy and varying degrees of associated memory loss. They analyzed stem cells from brain tissue removed during epilepsy surgery and evaluated the patients’ pre-surgery memory function.

In patients with low memory test scores, stem cells could not generate new nerve cells in laboratory cultures, but in patients with normal memory scores, stem cells were able to proliferate. That showed, for the first time, a clear correlation between patients’ memory and the ability of their stem cells to generate new nerve cells. The scientists said that the work is potentially applicable beyond epilepsy, but first, more studies have to be done with larger numbers of patients and more detailed testing of related brain structures and function. In addition, researchers still need to figure out how exactly the newly generated nerve cells contribute to learning and memory.

 

Potential therapy

Obviously, even the guy who forgot his wife’s name is not going to get neuronal stem cell implanted into his brain anytime soon. But there is a ray of hope. Extensive research is already being done to identify the natural substances, most likely growth factors peptides, which activate stem cells to form mature nerve cells, involving the use of fMRI and PET imaging techniques. One can envision the use of such peptides in stimulating the formation of new neurons. Better yet, drug developers could dream up (while sitting at their computers) drugs that would mimic the inactions of these peptides. I can already hear the drug commercial featuring an 80-year-old memory whiz who could recite the restaurant menu of last night’s outing with…what’s her name?

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.