In one of the first known laboratory studies that explores memory deficits associated with a viral infection of the central nervous system, Mayo Clinic researchers have evidence that this infection can lead to memory loss late in life. The study, which was conducted in animal models, suggests that over the lifetime of an individual, a picornavirus-related infection could possibly have a permanent effect on memory late in life.

“Our study suggests that virus-induced memory loss could accumulate over the lifetime of an individual and eventually lead to clinical cognitive memory deficits,” according to Charles L.

Howe, Ph.D., a Mayo Clinic neuroscientist and corresponding author of the study that appears on the cover of the November issue of Neurobiology of Disease. The study’s first author is Eric J. Buenz, Ph.D., a recent graduate of the molecular neuroscience program at Mayo Graduate School.

Picornaviruses are the most common infectious viral agents in humans. They are a family of viruses that include rhinoviruses, which is a virus associated with the common cold; enteroviruses, a virus associated with respiratory and gastrointestinal ailments; encephalitis, inflammation of the brain; myocarditis, inflammation of heart muscle; and meningitis.

Other viruses in this family include those that cause foot-and-mouth disease, polio and hepatitis A. Researchers were intrigued by the possibility of a link between picornavirus infections and memory loss. Little has been published in this area, Dr. Howe says.

In the study, mice were infected with Theiler’s murine (mouse) encephalomyelitis virus (comparable to the human poliovirus). Researchers looked for signs of spatial memory loss in the mice. Mice that contracted the virus had difficulty learning to navigate a maze designed to test various components of spatial memory. The degree of memory impairment, which ranged from no discernable damage to complete devastation, was directly correlated to the number of dead brain cells in the hippocampus region of the mouse’s brain.

Picornaviruses infect more than one billion people worldwide each year. Generally individuals contract two or three enterovirus and/or rhinovirus infections each year. In some cases the viruses get into the brain, and in some children these viruses can cause long-lasting brain injuries. “We think picornavirus family members cross into the brain and cause a variety of brain injuries. For example, the polio virus can cause paralysis. It can injure the spinal cord and different parts of the brain responsible for motor function. In the murine virus we studied, it did the same thing and also injured parts of the brain responsible for memory,” Dr. Howe says.

Enteroviruses and rhinoviruses are among the most common in the picornavirus family. Certain enteroviruses (gastrointestinal illnesses among others), such as enterovirus 71, are common in Asia, particularly southeast Asia where many children are infected. Once the virus infects the host due to unsanitary conditions, it can cross over into the brain and cause encephalitis, which can lead to conditions ranging from lethargy to a coma. In recent years, scores of children have died from infection.

The degree of brain damage in humans infected with a picornavirus infection is not known, but the evidence from the mouse study suggests this is an area of research that should be explored further.

“Our findings suggest that picornavirus infections throughout the lifetime of an individual may chip away at the cognitive reserve, increasing the likelihood of detectable cognitive impairment as the individual ages. We hypothesize that mild memory and cognitive impairments of unknown etiology may, in fact, be due to accumulative loss of hippocampus function caused by repeated infection with common and widespread neurovirulent picornaviruses. Further analysis of such deficits and exploration of potential therapeutic interventions is clearly needed,” the authors wrote.

Clinical case studies indicate that picornavirus infections in humans may be associated with inflammation of the brain and damage to the hippocampus - the part of the brain responsible for forming, storing and processing memory. Inflammation-induced damage to the brain is believed to be associated with learning and memory deficits.

Because picornaviruses are widespread and infection is common, the potential for this family of viruses to damage the human brain presents a very real medical problem, Dr. Howe says.

In general, viruses that kill neurons in the hippocampus are not uncommon. For example infections caused by the herpes virus or human immunodeficiency virus (HIV) can lead to the loss of brain cells, but while brain damage from these viruses is based on a persistent infection, brain damage from a picornavirus infection occurs only during the acute phase of infection.

“Because they are all related, by studying one, we may learn something about all of them. My hope is that we will learn something about the virus and the serious illnesses associated with other viruses in this family,” Dr. Howe says.

“Because hippocampus injury was correlated with reduced spatial memory formation across a range of damage and a range of memory performance, we suggest that picornavirus infection of the human central nervous system is likely to result in at least some degree of neurological deficit,” the authors write.

The study was funded by grants from the National Multiple Sclerosis Society; National Institutes of Health; a gift from Donald and Francis Herdrich; and the Mayo Graduate School.