Environmental Factor, August 2011, National Institute of Environmental Health Sciences
Neurobiologist McPherson wins travel award to meeting in Athens
Over the past decade as McPherson has worked in the lab and pursued his doctorate, he has also co-authored ten studies published by Harry's group, including one the journal Brain, Behavior, and Immunity (see story(http://www.niehs.nih.gov/news/newsletter/2011/august/science-journal/)) will highlight in a press release. (Photo courtesy of Steve McCaw)
The first time NIEHS Neurotoxicology Group(http://www.niehs.nih.gov/research/atniehs/labs/ntp/nt/staff.index.cfm) Technician Chris McPherson won a travel award to present his research at the annual meeting of the International Society for Neurochemistry (ISN), nature had other things in store. A category five hurricane lashed the coast of Cancun, Mexico, where the meeting was to be held, cancelling travel.
This summer, however, McPherson is confident he will fly to Athens, Greece for the 23rd biennial meeting(http://www.isn2011.org/) of ISN(http://www.neurochemistry.org/) and the European Society for Neurochemistry Aug. 28-Sept. 1. McPherson is taking advantage of a prestigious, highly competitive travel award(http://isn.kenes-international.com/Activities/CommitteeforAidandEducationinNeurochemistry/CAENGuidelines.aspx) to present his research, “Potential contribution of resident microglia during injury-induced neurogenesis” (see text box) at the meeting.
McPherson is first author on the study with a prior NIEHS postdoctoral fellow, Andrew Kraft, Ph.D., as co-author, and Jean Harry, Ph.D.(http://www.niehs.nih.gov/research/atniehs/labs/ntp/nt/index.cfm), as lead author. Harry is NIEHS Neurotoxicology Group principal investigator, McPherson's supervisor, and his advisor in the Curriculum in Toxicology(http://www.med.unc.edu/toxicology/people/) at the University of North Carolina at Chapel Hill, where Harry holds an appointment as an adjunct faculty member.
Finding career direction at NIEHS
McPherson came to NIEHS as a summer intern in 1999 with Harry's group. At the time he was completing his undergraduate work in cell biology at Arizona State University and wondering what he wanted to do with his future. He returned after graduation in 2000 as an Intramural Research Training Award postbaccalaureate fellow in the group, as he said, “To make sure it's really what I wanted to do.”
When McPherson finished his year as a postbac, instead of going to graduate school right away, he stayed on with Harry as a lab technician. By 2005, however, he'd decided to enter the Curriculum in Toxicology program with Harry as his advisor on the thesis he plans to defend in the fall. If everything goes as anticipated, McPherson will graduate with his Ph.D. in toxicology this December.
During his time with the group, McPherson has been Harry's protégée and advisee, as well as a mentor for summer interns in the lab. Among the bright young students McPherson has helped over the years is former Cary Academy student Anirudh Kota, who presented research he conducted with McPherson and Harry at the 2007 Society of Toxicology Annual Meeting and ToxExpo (see story(http://www.niehs.nih.gov/news/newsletter/2007/february/spotlight-kota.cfm)). This summer, Harry and McPherson are working with summer intern Amanda McLean, a student at Oakland University and Shreya Das, a high school student at Chapel Hill High.
Deciding on the next big step
McPherson plans to continue working in the Neurotoxicology Group for the time being, at least until he has time to weigh his options for further career development. Harry's group is one of several that will become part of the new Division of NTP laboratory to be headed by NTP Principal Investigator Mike Waalkes, Ph.D., a development that McPherson thinks may open new opportunities for integrative research targeted toward human health.
“I'm interested in learning more about NTP and how its research on the potential toxicity of environmental agents helps shape regulatory decisions by such agencies as the [U.S.] Food and Drug Administration and the [U.S.] Environmental Protection Agency,” he said. “I have received offers for post-doctoral fellowships, but I plan to weigh several options before I finally make a decision about my next step.”
New findings about the brain's self repair after injury
McPherson's presentation is based on research he and his co-authors published in the February 2011 issue of Neurotoxicity Research(http://www.springerlink.com/content/uk36q1m66767v02t/) . His abstract for the meeting, below, offers an expanded context for their findings:
Adult neurogenesis occurs in the subgranular zone (SGZ) of the hippocampal dentate gyrus, generating new dentate granule neurons. This process can be induced with brain injury, suggesting a capacity for self-repair in the hippocampus. Both resident microglial cells and infiltrating macrophages produce inflammatory molecules in response to brain injury.
While inflammation has been reported to be detrimental to hippocampal neurogenesis, other studies have suggested, rather, that the localized inflammatory response and stimulation of microglial cells can promote neurogenesis. Thus the question arises, what distinguishes beneficial versus adverse effects of inflammation on neurogenic self-repair? It is our group's working hypothesis that activated resident microglia may serve a supportive role during injury-induced neurogenesis in the hippocampus.
To examine our hypothesis, we used the hippocampal toxicant, trimethyltin (TMT; 2.3 milligrams per milliliter, ip), as a tool to selectively target dentate granule cell death in adolescent CD-1 male mice. Within 48 hours post-TMT, neuronal death is accompanied by resident microglia activation, and elevations in tumor necrosis factor alpha (TNFα) and interleukin-1α (IL-1α) mRNA levels. Bromodeoxyuridine (BrdU) incorporation identified the peak time of neurogenesis as coinciding with peak of neuroinflammation.
BrdU+ cells were transiently in contact with process-bearing microglia within the SGZ and inner granule cell layer (GCL). The proliferative response was sufficient to fully repopulate neurons in the GCL and provide functional recovery. Using laser-capture microdissection, SGZs were isolated at 48 hours post-TMT for qPCR analysis. Key molecules in the interleukin-1α pathway were induced by TMT exposure. Effects of IL-1α [150 picograms per milliliter] were identified in the proliferation and differentiation of hippocampal neural progenitor cells (NPCs) in vitro.
These data suggest a role for resident microglia and secreted IL-1α in regulation of NPC proliferation and differentiation for self-repair following chemical-induced hippocampal injury.