Papers of the Month
By Sara Mishamandani Amolegbe
SV2C role in dopamine release and Parkinson’s disease
NIEHS grantees discovered that the synaptic vesicle glycoprotein 2C (SV2C), a protein that helps regulate the release of neurotransmitters in the brain, might play a role in Parkinson’s disease (PD). The study findings suggested that SVC2 disruption is a feature of PD, and that SVC2 may be important for release of the neurotransmitter dopamine.
The researchers bred mice lacking SVC2 and found that these mice showed reduced dopamine levels in the brain and displayed decreases in motor activity. Previous studies linked dopamine disruption to PD, progressive cell loss, and increased vulnerability to toxicants.
The deletion of SVC2 in mice was also associated with a reduced response to nicotine, a chemical in cigarette smoke that was previously linked to a reduced risk of PD. Because they linked SVC2 disruption to both nicotine response and dopamine release, the authors suggested that the SV2C gene might be a factor for this previously identified association between nicotine use and reduced risk of PD.
The researchers also looked at the potential involvement of SV2C by examining postmortem human brain tissue. Compared with patients without a neurological disease, levels of SVC2 were dramatically reduced in brain tissue from patients with PD, but this was not the case for patients with Alzheimer’s disease or other neurological diseases.
Citation: Dunn AR, Stout KA, Ozawa M, Lohr KM, Hoffman CA, Bernstein AI, Li Y, Wang M, Sgobio C, Sastry N, Cai H, Caudle WM, Miller GW. 2017. Synaptic vesicle glycoprotein 2C (SV2C) modulates dopamine release and is disrupted in Parkinson disease. Proc Natl Acad Sci U S A 114(11):E2253−E2262.
Physically demanding or night-shift work linked to markers of fertility
Lifting heavy loads at work and working non-daytime schedules might be linked to decreased fertility, according to a new study by NIEHS grantees. The researchers reported that these occupational factors were associated with fewer mature eggs and fewer total eggs in the ovaries of study participants. Fewer eggs could lead to decreased fertility.
The researchers studied nearly 500 women seeking infertility treatment at Massachusetts General Hospital from 2004 to 2015. Markers of fertility were measured, including hormone levels, numbers of mature eggs capable of developing into healthy embryos, and structures in the ovary that indicated the number of immature eggs. The team analyzed associations between these markers and what the women reported on a questionnaire about their job demands and schedules.
Overall, women who reported moving or lifting heavy loads at work averaged 8.8 percent fewer total eggs and 14.1 percent fewer mature eggs compared with women who reported never lifting or moving heavy objects at work. Non-daytime schedules, including working at night or rotating shifts, were also associated with fewer eggs. The association between heavy lifting and decreased mature egg yield was even stronger among women who were overweight or obese, and those aged 37 years or older.
Although previous studies demonstrated a link between work schedule and physical factors and fertility, none were able to directly measure biological markers of fertility, such as reproductive hormones or ovarian function. Markers associated with egg yields did show an association with occupational factors, but hormone levels did not, suggesting that lower eggs yields might be an important factor that affects the relationship between physically demanding or night-shift work and fertility.
Citation: Mínguez-Alarcon L, Souter I, Williams PL, Ford JB, Hauser R, Chavarro JE, Gaskins AJ; Earth Study Team. 2017. Occupational factors and markers of ovarian reserve and response among women at a fertility centre. Occup Environ Med; doi:10.1136/oemed-2016-103953 [Online 6 February 2017].
Diazinon alters gut microbiome in sex-specific manner
In a new study, NIEHS grantees reported that exposure to the organophosphate insecticide diazinon altered the gut microbiome of mice. The changes to the microbiome were more pronounced in male mice than in female mice.
To investigate the impact of diazinon exposure on gut microbiome composition and its metabolic functions in mice, the researchers combined sequencing and mass spectrometry−based approaches. They found that exposure to diazinon altered the microbial community structure and metabolic profile in the gut of both male and female mice after a 13-week exposure, but male mice showed relatively stronger responses.
Because previous studies demonstrated a connection between changes in the gut microbiome and neurotoxicity, the authors suggested that this sex-dependent sensitivity might be associated with differences in the neurotoxicity of diazinon in male and female animals, which was also reported in other studies.
According to the researchers, these findings could provide novel insights into the specific changes to the microbial community and metabolic profile of the gut microbiome after exposure to diazinon, as well as the function of the microbiome as a potential mechanism that contributes to diazinon neurotoxicity.
Citation: Gao B, Bian X, Mahbub R, Lu K. 2017. Sex-specific effects of organophosphate diazinon on the gut microbiome and its metabolic functions. Environ Health Perspect 125(2):198−206.
New digital method helps researchers offer personal exposure results
NIEHS grantees developed a digital tool to communicate individual exposure results and environmental health information to study participants. A prototype of the Digital Exposure Report-Back Interface(DERBI) automates many of the time-intensive processes associated with producing personalized reports of exposure study results.
DERBI can generate user-centered reports, including comparisons with the study group and with benchmark populations. Each report includes the chemical found, health concerns raised by the exposures, actions people can take to protect their health, and an explanation of the study’s overall findings.
The researchers worked with the Centers for Disease and Control and Prevention Green Housing Study and the Child Health and Development Studies to refine and field test DERBI with culturally and economically diverse participants. User feedback showed that many participants understood their results and found the report helpful.
As a next step, the researchers are working to adapt DERBI to report results for four more studies and are conducting detailed analysis of participants’ experiences. The goal of DERBI is to help study participants understand the connections between exposures and health, and to provide participants with knowledge to make informed choices to help reduce harmful exposures.
Citation: Boronow KE, Susmann HP, Gajos KZ, Rudel RA, Arnold KC, Brown P, Morello-Frosch R, Havas L, Brody JG. 2017. DERBI: a digital method to help researchers offer "right-to-know" personal exposure results. Environ Health Perspect 125(2):A27−A33.