Abstract
Early life exposures to environmental contaminants are implicated in the pathogenesis of many neurodevelopmental disorders (NDDs). These disorders often display sex biases, but whether environmental neurotoxicants act in a sex-dependent manner to modify neurodevelopment is largely unknown. Since altered dendritic morphology is associated with many NDDs, we tested the hypothesis that male and female primary mouse neurons are differentially susceptible to the dendrite-promoting activity of 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95). Hippocampal and cortical neuron-glia co-cultures were exposed to vehicle (0.1% dimethylsulfoxide) or PCB 95 (100 fM-1 μM) from day in vitro 7-9. As determined by Sholl analysis, PCB 95-enhanced dendritic growth in female but not male hippocampal and cortical neurons. In contrast, both male and female neurons responded to bicuculline with increased dendritic complexity. Detailed morphometric analyses confirmed that PCB 95 effects on the number and length of primary and nonprimary dendrites varied depending on sex, brain region and PCB concentration, and that female neurons responded more consistently with increased dendritic growth and at lower concentrations of PCB 95 than their male counterparts. Exposure to PCB 95 did not alter cell viability or the ratio of neurons to glia in cultures of either sex. These results demonstrate that cultured female mouse hippocampal and cortical neurons are more sensitive than male neurons to the dendrite-promoting activity of PCB 95, and suggest that mechanisms underlying PCB 95-induced dendritic growth are sex-dependent. These data highlight the importance of sex in neuronal responses to environmental neurotoxicants.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 95-109 |
| Number of pages | 15 |
| Journal | Toxicological Sciences |
| Volume | 168 |
| Issue number | 1 |
| DOIs | |
| State | Published - Mar 1 2019 |
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Keywords
- dendritic arborization
- primary culture
- sholl analysis
ASJC Scopus subject areas
- Toxicology
Cite this
Sex-Dependent Effects of 2,2′,3,5′,6-Pentachlorobiphenyl on Dendritic Arborization of Primary Mouse Neurons. / Keil, Kimberly P.; Sethi, Sunjay; Lein, Pamela J.
In: Toxicological Sciences, Vol. 168, No. 1, 01.03.2019, p. 95-109.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Sex-Dependent Effects of 2,2′,3,5′,6-Pentachlorobiphenyl on Dendritic Arborization of Primary Mouse Neurons
AU - Keil, Kimberly P.
AU - Sethi, Sunjay
AU - Lein, Pamela J
PY - 2019/3/1
Y1 - 2019/3/1
N2 - Early life exposures to environmental contaminants are implicated in the pathogenesis of many neurodevelopmental disorders (NDDs). These disorders often display sex biases, but whether environmental neurotoxicants act in a sex-dependent manner to modify neurodevelopment is largely unknown. Since altered dendritic morphology is associated with many NDDs, we tested the hypothesis that male and female primary mouse neurons are differentially susceptible to the dendrite-promoting activity of 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95). Hippocampal and cortical neuron-glia co-cultures were exposed to vehicle (0.1% dimethylsulfoxide) or PCB 95 (100 fM-1 μM) from day in vitro 7-9. As determined by Sholl analysis, PCB 95-enhanced dendritic growth in female but not male hippocampal and cortical neurons. In contrast, both male and female neurons responded to bicuculline with increased dendritic complexity. Detailed morphometric analyses confirmed that PCB 95 effects on the number and length of primary and nonprimary dendrites varied depending on sex, brain region and PCB concentration, and that female neurons responded more consistently with increased dendritic growth and at lower concentrations of PCB 95 than their male counterparts. Exposure to PCB 95 did not alter cell viability or the ratio of neurons to glia in cultures of either sex. These results demonstrate that cultured female mouse hippocampal and cortical neurons are more sensitive than male neurons to the dendrite-promoting activity of PCB 95, and suggest that mechanisms underlying PCB 95-induced dendritic growth are sex-dependent. These data highlight the importance of sex in neuronal responses to environmental neurotoxicants.
AB - Early life exposures to environmental contaminants are implicated in the pathogenesis of many neurodevelopmental disorders (NDDs). These disorders often display sex biases, but whether environmental neurotoxicants act in a sex-dependent manner to modify neurodevelopment is largely unknown. Since altered dendritic morphology is associated with many NDDs, we tested the hypothesis that male and female primary mouse neurons are differentially susceptible to the dendrite-promoting activity of 2,2′,3,5′,6-pentachlorobiphenyl (PCB 95). Hippocampal and cortical neuron-glia co-cultures were exposed to vehicle (0.1% dimethylsulfoxide) or PCB 95 (100 fM-1 μM) from day in vitro 7-9. As determined by Sholl analysis, PCB 95-enhanced dendritic growth in female but not male hippocampal and cortical neurons. In contrast, both male and female neurons responded to bicuculline with increased dendritic complexity. Detailed morphometric analyses confirmed that PCB 95 effects on the number and length of primary and nonprimary dendrites varied depending on sex, brain region and PCB concentration, and that female neurons responded more consistently with increased dendritic growth and at lower concentrations of PCB 95 than their male counterparts. Exposure to PCB 95 did not alter cell viability or the ratio of neurons to glia in cultures of either sex. These results demonstrate that cultured female mouse hippocampal and cortical neurons are more sensitive than male neurons to the dendrite-promoting activity of PCB 95, and suggest that mechanisms underlying PCB 95-induced dendritic growth are sex-dependent. These data highlight the importance of sex in neuronal responses to environmental neurotoxicants.
KW - dendritic arborization
KW - primary culture
KW - sholl analysis
UR - http://www.scopus.com/inward/record.url?scp=85062174897&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062174897&partnerID=8YFLogxK
U2 - 10.1093/toxsci/kfy277
DO - 10.1093/toxsci/kfy277
M3 - Article
C2 - 30395321
AN - SCOPUS:85062174897
VL - 168
SP - 95
EP - 109
JO - Toxicological Sciences
JF - Toxicological Sciences
SN - 1096-6080
IS - 1
ER -