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. 2015 Oct;75(10):1114-24.
doi: 10.1002/dneu.22206. Epub 2014 Jul 8.

Neonatal overexpression of estrogen receptor-α alters midbrain dopamine neuron development and reverses the effects of low maternal care in female offspring

Catherine Jensen Peña  1   2 , Frances A Champagne  2
Affiliations

Neonatal overexpression of estrogen receptor-α alters midbrain dopamine neuron development and reverses the effects of low maternal care in female offspring

Catherine Jensen Peña et al. Dev Neurobiol. 2015 Oct.

Abstract

Maternal behavior is dependent on estrogen receptor-alpha (ERα; Esr1) and oxytocin receptor (OTR) signaling in the medial preoptic area (MPOA) of the hypothalamus, as well as dopamine signaling from the ventral tegmental area (VTA) to forebrain regions. Previous studies in rats indicate that low levels of maternal care, particularly licking/grooming (LG), lead to reduced levels of MPOA ERα and VTA dopamine neurons in female offspring and predict lower levels of postpartum maternal behavior by these offspring. The aim of this study was to determine the functional impact on maternal behavior of neonatal manipulation of ERα in females that had experienced low versus high levels of postnatal maternal LG. Adenovirus expressing ESR1 was targeted to the MPOA in female pups from low and high LG litters on postnatal day 2-3. Overexpression of ESR1 in low LG offspring elevated the level of ERα-immunoreactive cells in the MPOA and of tyrosine hydroxylase cells in the VTA to that observed in high LG females. Amongst juvenile female low LG offspring, ESR1 overexpression also decreased the latency to engage in maternal behavior toward donor pups. These results show that virally mediated expression of ESR1 in the neonatal rat hypothalamus results in lasting changes in ESR1 expression through the juvenile period, and can "rescue" hormone receptor levels and behavior of offspring reared by low LG dams, potentially mediated by downstream alterations within reward circuitry. Thus, the transmission of maternal behavior from one generation to the next can be augmented by neonatal ERα in the MPOA.

Keywords: dopamine; estrogen receptor-alpha; maternal care; medial preoptic area; ventral tegmental area.

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Figures

Figure 1
Figure 1. Study design and ESR1 over-expression
(A) Timeline of maternal observations, virus injections, offspring maternal sensitization behavior testing, and brain collection. (B) ESR1-ir was detected in the MPOA and cortex of females that received neonatal injections of Ad-ESR1 (arrow heads), and not in animals that received Ad-GFP control injections. 3V, third ventricle. Higher magnification of Ad-ESR1 staining reveals primarily cell body staining within MPOA, with more tracts stained in cortical regions. (C) ESR1-ir cell counts in low and high LG offspring within the MPOA and cortex. ϕ, p<0.1 (low vs. high).
Figure 2
Figure 2. ERα-ir cells in the MPOA of control and Ad-ESR1 low and high LG offspring
(A) Representative images of total ERα-ir in the MPOA of control and Ad-ESR1 low and high LG offspring. 3V, third ventricle. Higher magnification confirms nuclear ERα-ir. (B) Mean ± SEM cells counted expressing ERα protein in the MPOA. *p<0.05 (compared to control) **p<0.01(low vs. high).
Figure 3
Figure 3. Maternal sensitization latencies of control and Ad-ESR1 low and high LG offspring
(A) Mean ± SEM latency (days) of juvenile females to show full maternal behavior toward donor pups. *p<0.05 (comparison to low LG control offspring). (B) Correlation between ERα-ir cells in the MPOA with maternal sensitization latency among offspring.
Figure 4
Figure 4. TH-ir cells in the ventral midbrain of control and Ad-ESR1 low and high LG offspring
(A) Representative images of total TH-ir in the VTA and SN (right hemisphere shown) of control and Ad-ESR1 low and high LG offspring. Higher magnification confirms cytoplasmic TH-ir. Mean ± SEM TH-ir cells counted in the (B) VTA as a whole and (C) PBP of the VTA. *p<0.05, **p<0.01 (comparison to low LG control offspring). (D) Correlation between TH-ir cells in the PBP with ERα-ir cells in the MPOA among offspring.
See this image and copyright information in PMC

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References

    1. Afonso VM, Grella SL, Chatterjee D, Fleming AS. Previous maternal experience affects accumbal dopaminergic responses to pup-stimuli. Brain Res. 2008;1198:115–123. - PubMed
    1. Afonso VM, King S, Chatterjee D, Fleming AS. Hormones that increase maternal responsiveness affect accumbal dopaminergic responses to pup- and food-stimuli in the female rat. Horm Behav. 2009;56:11–23. - PubMed
    1. Arling GL, Harlow HF. Effects of social deprivation on maternal behavior of rhesus monkeys. J Comp Physiol Psychol. 1967;64:371–377. - PubMed
    1. Benoit D, Parker KC. Stability and transmission of attachment across three generations. Child Dev. 1994;65:1444–1456. - PubMed
    1. Berlin LJ, Appleyard K, Dodge KA. Intergenerational continuity in child maltreatment: Mediating mechanisms and implications for prevention. Child Dev. 2011;82:162–176. - PMC - PubMed

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