Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Blood stem cell growth factor reverses memory decline in mice

06.07.2009
The new study shows GCSF impacts both bone marrow and brain to improve cognition

A human growth factor that stimulates blood stem cells to proliferate in the bone marrow reverses memory impairment in mice genetically altered to develop Alzheimer's disease, researchers at the University of South Florida and James A. Haley Hospital found.

The granulocyte-colony stimulating factor (GCSF) significantly reduced levels of the brain-clogging protein beta amyloid deposited in excess in the brains of the Alzheimer's mice, increased the production of new neurons and promoted nerve cell connections.

The findings are reported online in Neuroscience and are scheduled to appear in the journal's print edition in August.

GCSF is a blood stem cell growth factor or hormone routinely administered to cancer patients whose blood stem cells and white blood cells have been depleted following chemotherapy or radiation. GCSF stimulates the bone marrow to produce more white blood cells needed to fight infection. It is also used to boost the numbers of stem cells circulating in the blood of donors before the cells are harvested for bone marrow transplants. Advanced clinical trials are now investigating the effectiveness of GCSF to treat stroke, and the compound was safe and well tolerated in early clinical studies of ischemic stroke patients.

"GCSF has been used and studied clinically for a long time, but we're the first group to apply it to Alzheimer's disease," said USF neuroscientist Juan Sanchez-Ramos, MD, PhD, the study's lead author. "This growth factor could potentially provide a powerful new therapy for Alzheimer's disease – one that may actually reverse disease, not just alleviate symptoms like currently available drugs."

The researchers showed that injections under the skin of filgrastim (Neupogen®) -- one of three commercially available GCSF compounds -- mobilized blood stem cells in the bone marrow and neural stem cells within the brain and both of these actions led to improved memory and learning behavior in the Alzheimer's mice. "The beauty in this less invasive approach is that it obviates the need for neurosurgery to transplant stem cells into the brain," Dr. Sanchez-Ramos said.

Based on the promising findings in mice, the Alzheimer's Drug Discovery Foundation is funding a pilot clinical trial at USF's Byrd Alzheimer's Center. The randomized, controlled trial, led by Dr. Sanchez-Ramos and Dr. Ashok Raj, will test the safety and effectiveness of filgrastim in 12 patients with mild to moderate Alzheimer's disease

The researchers worked with 52 elderly mice, equivalent to the human ages of 60 to 80 years. About half (24) were mice genetically altered to develop symptoms mimicking Alzheimer's disease by the time they reach 5-months old. The others (28 normal, or non-Alzheimer's, mice) were not. The researchers confirmed through a series of tests that the Alzheimer's mice were memory impaired before beginning the experiments.

Some mice were treated for three weeks with injections of the GCSF compound filgrastim. At the end of study, the Alzheimer's mice treated with GCSF demonstrated clearly improved memory, performing as well on behavioral tests as their non-Alzheimer's counterparts. The Alzheimer's mice administered saline injections instead of GCSF continued to perform poorly. GCSF treatment did not boost the already excellent memory performance demonstrated by the non-Alzheimer's mice tested before the study began.

Further experiments showed that the size and extent of beta amyloid deposited in the brains of the Alzheimer's mice was significantly less in those treated with GCSF. Depending on their ages, mice treated with GCSF had a 36 to 42-percent reduction in beta amyloid, the protein considered a major culprit in the development of Alzheimer's disease.

GCSF reduced the burden of beta amyloid deposited in the brains of the Alzheimer's mice by several means, the researchers found. One was by recruiting reinforcements to clear beta amyloid accumulating abnormally in the brain. The growth factor prodded bone-marrow derived microglia outside the brain to join forces with the brain's already-activated microglia in eliminating the Alzheimer's protein from the brain. Microglia are brain cells that act as the central nervous system's main form of immune defense. Like molecular "Pac-men," they rush to the defense of damaged or inflamed areas to gobble up toxic substances.

The growth factor also appeared to increase the production of new neurons in the area of the brain (hippocampus) associated with memory decline in Alzheimer's disease and to form new neural connections.

"The concept of using GCSF to harness bone marrow-derived cells for Alzheimer's therapy is exciting and the findings in mice are promising, but we still need to prove that this works in humans," said Dr. Raj, a physician researcher at the Byrd Alzheimer's Center at USF Health.

In addition to Dr. Sanchez-Ramos, other authors of the Neuroscience paper were Shijie Song, PhD; Vasyl Sava, PhD; Briony Catlow, PhD; Xiaoyang Lin; Takashi Mori, PhD; Chuanhai Cao, PhD; and Gary Arendash, PhD.

- USF Health -

USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida's colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $360 million in research grants and contracts last year, USF is one of the nation's top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching.

Anne DeLotto Baier | EurekAlert!
Further information:
http://www.usf.edu

More articles from Life Sciences:

nachricht Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel

nachricht Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>