دانشمندان ماده ترکیبی را کشف کرده اند که می تواند ظرفیت تشکیل حافظه جدید را به موش های سالمند بازگرداند، و احتمالا شانس بقای نورون های جدید در مرکز حافظه مغز را نیز بهبود می دهد.  این پژوهش نشانه هایی در مورد یک ساز و کار عصب-حفاظی یافته است که می تواند به درمانی برای بیماری آلزایمر منتهی شود.

[به گفته یکی از هدایت کنندگان پژوهش:] "این ماده عصب-حفاظی که P7C3 نامیده می شود به دلیل ویژگی های مساعد دارویی خود بسیار نویدبخش است. ... آن [ماده] می تواند خورده شود، از موانع خون-مغز با تاثیرگذاری های درازمدت عبور کند، و در بسیاری از مراحل ساخت بدون خطری توسط موش ها تحمل گردد."

پژوهشگران یافته های خود در این باره را در شماره 9 جولای 2010 مجله علمی "سل" (یاخته) منتشر ساختند.  دکتر توماس اینسل ... گفت: "این نمایش برجسته ای از درمانی است که زوال شناختی ناشی از کهولت را در حیوانات زنده متوقف می کند و جهت به سوی تولید اولین دارویی را نشان می دهد که مرکز فرایند آسیب رسانی بیماری آلزایمر را هدف خواهد گرفت."

حرکت های فیزیکی، اجتماعی، و دیگر تجربه های غنی موجب تشدید [فرایند] تکوین عصبی، که در آن سلول های عصبی جدید متولد و بالغ می شوند،  می گردد.  این رشد در دندانه گیروس، ناحیه کلیدی در مرکز حافظه مغز یا هیپوکامپ است.  اما، حتی در مغز عادی بالغ هم بیشتر این سلول های تازه متولدشده در یک ماهی که طول می کشد تا این سلول ها رشد کرده و به مدارهای مغز متصل شوند می میرند.  این سلول ها می بایست برای بقا با کوهی از چالش ها مبارزه کنند.  سلول های عصبی نوزاده هیپوکامپ در اختلال های مرتبط با سالمندی، مانند آلزایمر، که با مرگ بدون کنترل این سلول ها شناخته می شود، سرنوشت بدتری دارند. 

به امید یافتن ماده ای که بتواند از سلول های عصبی آسیب پذیر در طول این فرایند محافظت کند، [پژوهشگران] بیش ار هزار مولکول کوچک را در موش های زنده آزمایش کردند.  یکی از این ترکیب ها، با نام P7C3 کاستی های مغز موش های بالغی، که دستکاری شده بود تا فاقد ژنی که برای بقای نورون های تازه متولد در هیپوکامپ لازم است باشد را جبران نمود. ...

Chemical Makes Brain Cells Grow, Thwarts Mental Decline in Aging Rats

ScienceDaily (July 8, 2010) — Scientists have discovered a compound that restores the capacity to form new memories in aging rats, likely by improving the survival of newborn neurons in the brain's memory hub. The research has turned up clues to a neuroprotective mechanism that could lead to a treatment for Alzheimer's disease.

"This neuroprotective compound, called P7C3, holds special promise because of its medication-friendly

properties," explained Steven McKnight, Ph.D., who co-led the research with Andrew Pieper, M.D., Ph.D., both of University of Texas Southwestern Medical Center, Dallas. "It can be taken orally, crosses the blood-brain barrier with long-lasting effects, and is safely tolerated by mice during many stages of development."

The researchers report on their findings July 9, 2010 in the journal Cell. Their work was funded, in part, by the NIH's National Institute of Mental Health (NIMH), a NIH Director's Pioneer Award funded through the Common Fund and managed by the National Institute of General Medical Sciences, and National Cancer Institute.

"This striking demonstration of a treatment that stems age-related cognitive decline in living animals points the way to potential development of the first cures that will address the core illness process in Alzheimer's disease," said NIMH Director Thomas Insel, M.D.

Physical activity, social, or other enriching experiences promote neurogenesis -- the birth and maturation of new neurons. This growth takes place in the dentate gyrus, a key area of the brain's memory hub, the hippocampus. But even in the normal adult brain, most of these newborn neurons die during the month it takes to develop and get wired into brain circuitry. To survive, the cells must run a gauntlet of challenges. Newborn hippocampus neurons fare much worse in aging-related disorders like Alzheimer's, marked by runaway cell death.

In hopes of finding compounds that might protect such vulnerable neurons during this process, Pieper, McKnight and colleagues tested more than 1000 small molecules in living mice. One of the compounds, designated P7C3, corrected deficits in the brains of adult mice engineered to lack a gene required for the survival of newborn neurons in the hippocampus. Giving P7C3 to the mice reduced programmed death of newborn cells -- normalizing stunted growth of branch-like neuronal extensions and thickening an abnormally thin layer of cells by 40 percent. Among clues to the mechanism by which P7C3 works, the researchers discovered that it protects the integrity of machinery for maintaining a cell's energy level.

To find out if P7C3 could similarly stem aging-associated neuronal death and cognitive decline, the researchers gave the compound to aged rats. Rodents treated with P7C3 for two months significantly outperformed their placebo-treated peers on a water maze task, a standard assay of hippocampus-dependent learning. This was traced to a threefold higher-than-normal level of newborn neurons in the dentate gyrus of the treated animals. Rats were used instead of mice for this phase of the study because the genetically engineered mice could not swim.

Prolonged treatment of aged rats with P7C3 also enhanced the birth of new neurons. "Aged rats normally show a decline in neurogenesis associated with an inability to form new memories and learn tasks," Pieper explained.

In their study, rats treated with P7C3 each day showed evidence of an increase in the formation of newborn neurons and significant improvements in their ability to swim to the location of a missing platform, a standardized test of learning and memory in rats.

The key to the treatment's success is the protection of newborn neurons, the researchers report. In fact, they explained, the normal process by which newborn neurons are incorporated into the brain as mature cells is a long and perilous one.

"It takes a long time -- two to four weeks -- from the birth of a new neuron until it becomes functional," McKnight said. "Most of them die along the way." P7C3 essentially seems to give newborn neurons better odds.

Notably, they say that two other drugs (Dimebon and Serono compounds) -- both of which bear structural similarities to P7C3 -also encourage the growth of new neurons. It's tempting to think that all three compounds work in the same way.

The researchers pinpointed a derivative of P7C3, called A20, which is even more protective than the parent compound. They also produced evidence suggesting that two other neuroprotective compounds eyed as possible Alzheimer's cures may work through the same mechanism as P7C3. The A20 derivative proved 300 times more potent than one of these compounds currently in clinical trials for Alzheimer's disease. This suggested that even more potent neuroprotective agents could potentially be discovered using the same methods. Following up on these leads, the researchers are now searching for the molecular target of P7C3 -- key to discovering the underlying neuroprotective mechanism.