A Genomic Response to Trace Fear Conditioning in the Amygdala of Female Rats After Developmental Exposure to Manganese
Citation:
Franklin, J., B. Chorley, V. Moser, W. Oshiro, T. Beasley, Kathy Mcdaniel, AND D. Herr. A Genomic Response to Trace Fear Conditioning in the Amygdala of Female Rats After Developmental Exposure to Manganese. SOT Annual Meeting, San Antonio, Texas, March 11 - 15, 2018.
Impact/Purpose:
Abstract for SOT annual meeting.
Description:
Increases in brain-derived neurotrophic factor (Bdnf), Ca2+/calmodulin-dependent protein kinase II alpha (Camk2a), and cyclic adenosine monophosphate (cAMP) response element binding (Creb1) gene expression have been associated with learning in a variety of different rodent studies. We examined whether perinatal exposure to manganese (Mn) influences gene expression of these three target genes associated with learning trace fear conditioning. Pregnant Long Evans rats were exposed to Mn, a neurotoxic environmental element, at 0, 0.5 or 1.3 g/l in drinking water throughout gestation and lactation. Starting at 97 days of age, offspring were trained with a trace fear conditioning protocol in which rats were exposed to a compound cue (light and tone) followed by 30 seconds (trace period) and a mild foot shock (1mA, 0.5 seconds). Five paired training sessions occurred to induce learning. Amygdalas were removed and flash frozen at 3 and 6 hours after initial trace fear conditioning. In female rats, quantitative RT-PCR data generated from amygdala sections (n=9-10/group) demonstrated significantly increased Camk2a expression in control offspring over time, from 3 to 6 h in control offspring and a dose response difference at the 6 h time point between the 0.5 and 1.3 g/l exposed groups (5.6 and 5-fold increase, respectively; p<0.05 one-way ANOVA with Tukey-Kramer post hoc analysis). There were no significant changes in the expression of these genes noted in male offspring or with the other genes measured in either sex. This indicates that Mn may influence the expression of Camk2a selectively in the female amygdala in response to this learning paradigm. On-going research will examine treatment-related changes in the offspring of dams concurrently exposed to Mn and varying prenatal stress, including transcriptional changes in the hippocampus or amygdala of adult offspring after learning the trace fear conditioning task. This abstract does not necessarily reflect EPA policy.