About the lab
The laboratory of Janice M. Juraska examines the dietary, hormonal, and xenobiotic influences across the lifespan on the neuroplasticity of cognitive-related brain regions and associated impacts on cognitive behavior. In particular, my initial project investigated a nutrient's effect on cognitive function and neuroanatomy in normal aging. Currently, I am investigating the effects of perinatal exposure to a class of endocrine-disrupting chemicals known as phthalates in combination with a maternal high-fat diet on indices of development, behavior, cognition, genetic expression, and neurotoxicity. Since our laboratory investigates neuroanatomical and behavioral consequences of hormonal influences, we inevitably study the hormone-sensitive periods of life and sex differences.
Featured research (7)
Bisphenol A (BPA) is an endocrine disruptor found in polycarbonate plastics and exposure in humans is nearly ubiquitous and it has widespread effects on cognitive, emotional, and reproductive behaviors in both humans and animal models. In our laboratory we previously found that perinatal BPA exposure results in a higher number of neurons in the adult male rat prefrontal cortex (PFC) and less play in adolescents of both sexes. Here we examine changes in the rate of postnatal apoptosis in the rat prefrontal cortex and its timing with brief BPA exposure. Because an increased number of neurons in the PFC is a characteristic of a subtype of autism spectrum disorder, we tested social preference following brief BPA exposure and also expression of a small group of genes. Males and females were exposed to BPA from postnatal days (P) 6 through 8 or from P10 through 12. Both exposures significantly decreased indicators of cell death in the developing medial prefrontal cortex in male subjects only. Additionally, males exposed to BPA from P6 – 8 showed decreased social preference and decreased cortical expression of Shank3 and Homer1, two synaptic scaffolding genes that have been implicated in social deficits. There were no significant effects of BPA in the female subjects. These results draw attention to the negative consequences following brief exposure to BPA during early development.
Phthalates are a class of endocrine disruptors found in a variety of consumer goods, and offspring can be exposed to these compounds during gestation and lactation. Our laboratory has found that perinatal exposure to an environmentally relevant mixture of phthalates resulted in a decrease in cognitive flexibility and in neuron number in the adult rat medial prefrontal cortex (mPFC). Here, we examine effects of phthalate treatment on prenatal cellular proliferation and perinatal apoptosis in the mPFC. To examine the phthalate effects on cellular proliferation, dams consumed 0, 1, or 5 mg/kg of the phthalate mixture daily from embryonic day 2 (E2) through the day of birth (P0), and on E16 and E17, they were injected with BrdU. The mPFC of offspring was analyzed on P5 and showed a decrease in labelled cells in the phthalate exposed groups. To examine whether changes in BrdU density observed on P5 were due to altered cell survival, cell death was measured on E18, P0, and P5 using a TUNEL assay in a separate cohort of prenatally exposed offspring. There was an increase in TUNEL labelled cells at E18 in the phthalate exposed groups. In the final experiment, dams consumed the phthalate mixture from E2 through P10, at which time mPFC tissue was stained with TUNEL. Phthalate treated subjects showed a higher density of apoptotic cells at P10. These results indicate both pre- and postnatal phthalate exposure increases apoptosis in the male and female rat mPFC. While the impact of phthalates on proliferation cannot be ruled out, these data do not allow for definitive conclusions.
In female rats, pubertal onset is associated with maturation of the medial prefrontal cortex (mPFC) and mPFC‐mediated behaviors. These behavioral and anatomical changes are likely due to effects of estrogens at the nuclear estrogen receptor beta (ERβ), which is expressed at higher levels than the estrogen receptor alpha (ERα) isoform in the adult mPFC. Researchers have previously quantified ERβ protein and Esr2 RNA in rodents during early postnatal development and adulthood, but an adolescent‐specific trajectory of this receptor in the mPFC has not been documented. Given that Esr2 expression can fluctuate in the presence or absence of estrogens, puberty and the subsequent rise in gonadal hormones could influence levels of ERβ in the adolescent brain. To further explore this, we used RNAscope to quantify the amount of Esr2 mRNA in pre‐pubertal adolescent, recently post‐pubertal adolescent, and adult female rats. We show here that Esr2 expression decreases significantly in the mPFC, striatum and motor cortex between pre‐pubertal adolescence and adulthood. In the mPFC, this decrease occurs rapidly at pubertal onset, with no significant decrease in Esr2 levels between the recently post‐pubertal and adult cohort. In contrast, the striatum and motor cortex had no significant differences in the amount of Esr2 mRNA between pre‐ and post‐pubertal females. Insofar as the amount of Esr2 expression is proportional to functional ERβ, these results suggest ERβ decreases in a region‐specific pattern in response to pubertal onset and highlight a role for this receptor in the maturational events that occur in the female rat mPFC at puberty.
Exposure to stress during adolescence is a risk factor for developing several psychiatric disorders, many of which involve prefrontal cortex (PFC) dysfunction. The human PFC and analogous rodent medial prefrontal cortex (mPFC) continue to mature functionally and anatomically during adolescence, and some of these maturational events coincide with pubertal onset. As developing brain regions are more susceptible to the negative effects of stress, this may make puberty especially vulnerable. To test this, we exposed male and female rats to isolation and restraint stress during the onset of puberty or during the post‐pubertal period of adolescence. In young adulthood, both stressed groups and an unstressed control group underwent testing on a battery of tasks to assess emotional and cognitive behaviors, and the volume of the mPFC was quantified postmortem. Factor analysis revealed only subjects stressed peri‐pubertally showed a long‐term deficiency compared to controls in prepulse inhibition. Additionally, both sexes showed volumetric mPFC decreases following adolescent stress, and these losses were most pronounced in females. Our findings suggest that pubertal onset may be a vulnerable window wherein adolescents are most susceptible to the negative consequences of stress exposure. Furthermore, it highlights the importance of accounting for pubertal status when studying adolescents.
The prefrontal cortex (PFC) is a late developing region of the cortex, and its protracted maturation during adolescence may confer a period of plasticity. Closure of critical, or sensitive, periods in sensory cortices coincides with perineuronal net (PNN) expression, leading to enhanced inhibitory function and synaptic stabilization. PNN density has been found to increase across adolescence in the male rat medial PFC (mPFC). Here, we examined both male and female rats at four time points spanning adolescent development to stereologically quantify the number and intensity of PNNs in the mPFC. Additionally, because puberty coincides with broad behavioral and neuroanatomical changes, we collected tissue from age-matched pre- and post-pubertal siblings within a litter. Results indicate that both males and females show an increase in the total number and intensity of mPFC PNNs between postnatal day (P) 30 and P60. As we have previously found, white matter under the mPFC also increased at the same time. Male puberty did not affect PNNs, while female pubertal onset led to an abrupt decrease in the total number of PNNs that persisted through mid-adolescence before increasing at P60. Despite the change in PNN number, the intensity of female PNNs was not affected by puberty. Thus, though males and females show increases in mPFC PNNs during adolescence, the pubertal decrease in the number of PNNs in female rats may indicate a difference in the pattern of maximal plasticity between the sexes during adolescence.