Commentary focuses on latest knowledge about inflammation and biology of aging brain

University of South Florida researchers from the Department of Neurosurgery and Brain Repair have published several articles in a special issue of the journal Aging and Disease, a peer-reviewed, open access journal focused on issues relating to the biology of aging and innovative therapies. The journal’s December 2010 issue is dedicated to research on the aging brain, the role of inflammation, and potential therapies for brain repair, including stem cell transplantation and other methods to therapeutically “tinker” with, or “modulate,” the inflammatory response.

The studies are accessible at the on-line version of Aging and Disease (http://aginganddisease.org/).

The cover image, supplied by USF neuroscientist Alison Willing, depicts human umbilical cord blood cells transplanted into hippocampal neurons (red) from an aging adult brain. Carmelina Gemma, right, was guest editor for the journal’s special edition highlighting the brain immune system’s role in aging and age-related diseases.

“The articles in this special issue summarize the current knowledge concerning inflammation in the aged brain,” said guest editor Carmelina Gemma, PhD, assistant professor in USF’s Department of Neurosurgery and Brain Repair and a research biologist at the James A. Haley Veterans’ Hospital. “While inflammation is normally considered damaging in aging and age-related neurodegenerative diseases, research is showing that in some cases inflammation is a therapeutic event that could be altered to benefit those suffering from Alzheimer’s disease and other disorders with inflammatory response.”

Studies on human umbilical cord blood cells

A laboratory study showed that human umbilical cord blood cells transplanted into experimental models of central nervous system aging, injury and disease provided a ‘trophic effect’ (nutritional effect) that enhanced survival and maturation of hippocampal neurons.

“As we age, cognitive function tends to decline,” said lead author Alison E. Willing, PhD, professor in the Department of Neurosurgery and Brain Repair. “Changes in cognitive function are accompanied by changes in the hippocampus, an area of the brain where long-term memory and other functions are located. The hippocampus is among the first to suffer the effects of diseases such as Alzheimer’s.”

Alison Willing, PhD

According to Dr. Willing and her USF co-authors, these changes contribute to stroke and dementia in the aging population as neural cells become more susceptible to stressors and disease processes.

“It is important to understand how these cells may be manipulated to support hippocampal function in order to develop new therapies,” she said. “This study sought to examine the potential of human umbilical cord blood cells to enhance proliferation and increase survival of hippocampal cells from aging adult rat brains.”

Inflammatory mediators examined

In another study published in the special issue, lead author Paula C. Bickford, PhD, a professor in the USF Department of Neurosurgery and Brain Repair and senior research biologist at the James A. Haley Veterans’ Hospital, reported that researchers examined an ‘inflammatory mediator’ involved in aging and neurodegenerative diseases associated with aging.

Dr. Bickford and her co-authors carried out a series of experiments on both young and old rats using tumor necrosis factor alpha (TNF-a) and anti-TNFa. TNF-a — a small signaling protein linked to inflammation response – increases with aging . The USF researchers evaluated the effects of TNF-a and anti-TFNa in modulating a classical conditioning behavior, eye blinking.

Paula Bickford, PhD

“When we treated young rats before eye blink training sessions, TNF-a significantly interfered with learning of conditioned responses,” explained Dr. Bickford. “On the other hand, when aged rats were treated with anti-TNF-a, improvements in their learned conditioned responses were observed and they were capable of learning faster than controls.”

Aging brain suffers “failure to communicate”

Drs. Gemma and Bickford also collaborated on a study examining whether communication between neurons and microglia (the immune cells of the brain) are disrupted in the aging brain and what role inflammation plays in the communication process.

“Microglia react to inflammation in the brain and provide an immune response that regulates inflammation,” Dr. Gemma said. “Recent evidence suggests that there is a kind of ‘cross talk’ between neurons and microglia. Interruption of this dialogue appears to be associated with a decline in physiological processes of neuron renewal as well as exacerbation of diseases such as Alzheimer’s and Parkinson’s.”

They concluded that it would be valuable to know more about how neuron-microglia signaling dysfunction leads to cognitive impairment and how the disruption might be “manipulated for preventive and therapeutic purposes.”

“As the Baby Boom generation reaches its seniority, the University of South Florida’s many clinical and laboratory resources are increasingly being applied to critical questions about aging,” said neuroscientist Paul R. Sanberg, DSc, PhD, senior associate vice president for the USF Office of Research and Innovation. “The neuroscience researchers contributing to this special issue of Aging and Disease are at the forefront of this effort.”

Story by Randolph Fillmore, USF Center of Excellence for Aging and Brain Repair