Researchers image a biomarker of neurogenesis

Nov 13 2007

Mirjana Maletic-Savatic, M.D., Ph.D, and co-investigators from Stony Brook University Medical Center, Brookhaven National Laboratory and Cold Spring Harbor Laboratory have discovered a way to image a biomarker of neural stem and progenitor cells (NPCs) in the living human brain.

This discovery allows researchers to monitor neurogenesis, the development of nerve tissues. The finding may also prove to be monumental in the diagnosis and treatment of multiple sclerosis, Parkinson's disease, depression, and other disorders of the central nervous system where neurogenesis is disrupted. The investigators are the first in the world to detect NPCs in this way. Their findings are published in the November 9 issue of the journal Science.

By using magnetic resonance spectroscopy (MRS), the investigative team found a way to detect a biomarker of NPCs that is a reference for monitoring neurogenesis. Until now, scientists could not monitor neurogenesis in the human brain. Research indicates that in certain regions of the human brain, NPCs are produced into adulthood and thus may give rise to new neurons. The team studied NPCs in one of those regions, thought to be a center for learning and memory.

"Our findings open the possibility of investigating the role of NPCs and neurogenesis in a wide variety of human brain disorders," says Dr. Maletic-Savatic, Lead Investigator and Assistant Professor of Neurology, who points out that their method is the first non-invasive approach to identify NPCs in the human brain. "We are using the method as a protocol to study changes that occur in neurological diseases."

Dr. Maletic-Savatic cited collaborative work at Stony Brook with Lauren Krupp, M.D., Professor of Neurology and a specialist in multiple sclerosis (MS), as an example of potential clinical applications to the research team's discovery of the new NPC imaging method. Dr. Maletic-Savatic is imaging NPC recruitment in brain regions of MS patients.

"This method has immense clinical applications for treating MS," says Dr. Krupp. "Dr. Maletic-Savatic's approach is groundbreaking in that it is fundamental to the prospect of stem cell therapy for this debilitating disease."

Dr. Maletic-Savatic also plans to develop other studies that will test the usefulness of MRS to quantify and characterize neurogenesis for many patients. These include patients who have traumatic brain injuries, stroke, epilepsy, Parkinson's disease and even cancer, as some scientists believe brain tumors are associated with abnormal proliferation of NPCs. Furthermore, Dr. Maletic-Savatic plans to study the role NPCs play in early human development, as the method is safe to use in prematurely born babies and young children.

Scientists have been able to identify NPCs in animals by way of various imaging techniques. But those techniques require a labeling of cells with radioactive agents or other agents or drugs. Such methods are not safe in humans. By identifying the biomarker in NPCs, the researchers could image NPCs without the use of agents. This method was validated in animal models in a collaborative effort with Helene Benveniste, M.D., Ph.D., Professor in the Department of Anesthesiology at Stony Brook, and head of the mMRI laboratory at BNL.

Dr. Maletic-Savatic says that a crucial component to the investigative procedure is the development of a method for processing of the MRS data. This method, developed by Petar M. Djuric, Ph.D., Professor of Electrical and Computer Engineering, Stony Brook University, enabled the team to detect NPCs in vivo and in low concentrations. The signal processing method allowed the researchers to separate the biomarker from other signals in the brain in the MRS data.

To date, the researchers have analyzed the NPC biomarker in the rodent brain and hippocampus of live humans. In their investigations in humans, the researchers observed major differences in the concentrations of the biomarker between two regions, the hippocampus and cortex. They also used MRS to image the brains of people at various ages. They found that the biomarker decreased with age.

According to Dr. Maletic-Savatic, the multidisciplinary team of neurobiological scientists, imaging experts, biomedical engineers, neurologists and other physician specialists from Stony Brook University, BNL, and CSHL will further investigate how effective MRS is in identifying and characterizing NPCs, as well as examine what relationship the cells have to neurogenesis and disease development.

Dr. Maletic-Savatic's co-authors on the study published in the November 9 issue of Science, titled "Magnetic Resonance Spectroscopy Identifies Neural Progenitor Cells in the Live Human Brain," include: Louis N. Manganas, M.D., Ph.D., of SBU and CSHL; Xueying (Sherry) Zhang, Ph.D., of SBU; Yao Li, a Ph.D. student at SBU; Raphael D. Hazel, Ph.D., of SBU; S. David Smith, Ph.D., of BNL; Mark E. Wagshul, Ph.D., of SBU; Fritz Henn, M.D., Ph.D., of BNL; Helene Benveniste, M.D., Ph.D., of SBU and BNL; Petar M Djuric, Ph.D., of SBU, and Grigori Enikolopov, Ph.D., of CSHL.

The research is supported by the National Institutes of Health (NIH). Funding for previous and current investigation includes the NIH's National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).