Seeking insight into the cause
of a silent killer

Could furry, four-legged creatures help determine the cause of Sudden Infant Death Syndrome (SIDS)? Assistant Professor of Biology Jeffery Erickson and a team of independent research students are working to determine just that.

SIDS is the leading killer of human infants aged one month to one year, according to The National Institutes of Health, and recent research suggests that defects in the production of serotonin in the brain could be linked to SIDS deaths. “Serotonin is a neurochemical that has a powerful excitatory effect on breathing, especially in young animals,” Erickson said.

A leading hypothesis proposes that SIDS results from the failure of protective respiratory responses to life-threatening environmental stressors (“triggers”) during a critical period after birth in infants with underlying abnormalities in brainstem serotonin neurons.

For several years, Erickson has studied the respiratory behavior of Pet-1 knockout mice—genetically engineered mice that have only 30 percent of the normal number of serotonin neurons in the brain. Erickson’s research, which began at Case Western Reserve University and has continued at TCNJ since 2003, has shown that the Pet-1 knockout mice have SIDS-like characteristics. The loss of serotonin neurons results in depressed and irregular breathing at birth, and approximately 25–30 percent of the knockouts die suddenly during the first postnatal week. In addition, the severity of breathing problems in the knockouts can be influenced by environmental conditions.

But Erickson’s studies also showed that, after 10 days, the initial breathing abnormalities in the surviving knockout mice resolve spontaneously. Therefore, it appears that “the defect [in serotonin] provides susceptibility” to sudden early death, “but doesn’t mean that death is going to occur,” Erickson explained. “The key as to whether an individual dies or not may relate to whether it encounters a trigger” within a critical period after birth.

Erickson and his team are now exposing newborn knockout mice to environmental variables that are known risk factors for SIDS and looking to see if any exacerbate the animals’ already abnormal respiratory behavior. Although Erickson stressed that he is “not doing SIDS research per se,” he has a keen interest in determining whether the Pet-1 mice could provide insights into the etiology of SIDS, since there is currently no good animal model for this devastating condition.

Erickson’s research is ongoing and continues to yield interesting new data. Brian Sposato, a senior biology major, worked with Erickson last year to test whether the Pet-1 knockouts are capable of auto-resuscitation, a last ditch effort to re-initiate breathing following apnea produced by exposure to very low oxygen levels. A failure to auto-resuscitate from prolonged apnea has long been postulated in SIDS. Their research determined that the knockout mice can auto-resuscitate “to a single exposure to low oxygen levels”; however, their ability to do so is “much less efficient” than mice with normal serotonin levels, Erickson said.

Considering the suggested link between SIDS deaths and a baby’s inability to auto-resuscitate, Erickson is pursuing these new findings “vigorously.” He and Sposato have written up their study and are submitting the work for peer review.

Erickson is currently working with four undergraduate independent research students. The experience the students are gaining is invaluable. “They are very actively involved with the research” helping to define the project, design experiments, collect and analyze data, and suggest ways to do things better, Erickson explained.

Amanda Harris, a junior biology/Spanish double major, is researching temperature effects on the knockout’s auto-resuscitation capabilities. “Being involved in research has given me the opportunity to apply what I have learned in my studies to something tangible, to something I can truly call my own and be proud of,” Harris said.

Samantha Mecker, a junior biology/French double major, is working with knockouts that have received a constant exposure to nicotine during development in utero. Prenatal exposure to nicotine is a recognized risk factor for SIDS.

Amanda Ganza, a junior biology/psychology double major, is examining the function of the remaining serotonin cells in the knockout brain by pre-treating animals with a serotonin receptor blocker prior to ventilatory testing. In a related study, Ramon Davila, a junior biology major, is looking at the effects of serotonin receptor blockade on the knockout’s ventilatory response to increased carbon dioxide levels. “What I take from this experience…is the knowledge and confidence in being able to work in research laboratories in the future,” Davila said.

For Sposato, the most extraordinary part was speaking about his work at last year’s Society for Neuroscience Annual Conference in Atlanta. “Here I was, an undergraduate, and I was presenting research at one of the premier meeting for neuroscientists across the globe.”