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Age-Dependent Effects of Prenatal Stress on the Corticolimbic Dopaminergic System Development in the Rat Male Offspring

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Abstract

We have previously demonstrated that prenatal stress (PS) exerts an impairment of midbrain dopaminergic (DA) system metabolism especially after puberty, suggesting a particular sensitivity of DA development to variations in gonadal hormonal peaks. Furthermore we demonstrated that PS alters the long term androgens profile of the rat male offspring from prepubertal to adult stages. In this work we evaluated the sexual hormones activational effects on the DA system by analysing PS effects on the dopaminergic D2-like (D2R) and on the gonadal hormones receptor levels on cortical and hippocampal areas of prepubertal and adult male offspring. We further evaluated the dendritic arborization in the same areas by quantifying MAP2 immunoexpresion. Our results show that PS affected oestrogen receptor alpha (ERα) expression: mRNA er1s and ERα protein levels were decreased on prefrontal cortex and hippocampus of adult offspring. Moreover, PS reduced D2R protein levels in hippocampus of prepubertal rats. Morphological studies revealed that prepubertal PS rats presented decreased MAP2 immunoexpression in both areas suggesting that PS reduces the number of dendritic arborizations. Our findings suggest that PS exerts long-term effects on the DA system by altering the normal connectivity in the areas, and by modulating the expression of D2R and ERα in an age-related pattern. Since the developing forebrain DA system was shown to be influenced by androgen exposure, and PS was shown to disrupt perinatal testosterone surges, our results suggest that prenatal insults might be affecting the organizational role of androgens and differentially modulating their activational role on the DA development.

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Acknowledgments

We are grateful to Dr. Trinidad Saez for her help in image analysis of the data and to Dr. Sandra Zárate for her skillful technical assistance in the Western blot studies. We are also indebted to Martin Brahamian and Mercedes Imsem for their help and supervision of the rats management and care. The skillful technical assistance and bibliographical managements of Mrs Susana Buglione is greatly appreciated. This research was supported by grants from CONICET (PIP 2065) and ANPCYT (PICT 31981 and PICT 0040). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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  1. Carlos Javier Baier

    Present address: Instituto de Investigaciones Bioquímicas de Bahía Blanca, CC 857, B8000FWB, Bahía Blanca, Argentina

  2. María Eugenia Pallarés

    Present address: Instituto de Biología Celular y Neurociencias “Prof. E. De Robertis” (IBCN), Paraguay 2155, 3°Piso, C1121ABG, Buenos Aires, Argentina

Authors and Affiliations

  1. Instituto de Química y Fisicoquímica Biologicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina

    María Eugenia Pallarés, Carlos Javier Baier, Ezequiela Adrover & Marta Cristina Antonelli

  2. Instituto de Investigaciones Biotecnológicas, Universidad de San Martín, San Martín, Buenos Aires, Argentina

    Melisa Carolina Monteleone & Marcela Adriana Brocco

  3. Instituto de Biología Celular y Neurociencias “Prof. E. De Robertis” (IBCN), Paraguay 2155, 3°Piso, C1121ABG, Buenos Aires, Argentina

    Marta Cristina Antonelli

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  1. María Eugenia Pallarés
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Correspondence to Marta Cristina Antonelli.

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Pallarés, M.E., Baier, C.J., Adrover, E. et al. Age-Dependent Effects of Prenatal Stress on the Corticolimbic Dopaminergic System Development in the Rat Male Offspring. Neurochem Res 38, 2323–2335 (2013). https://doi.org/10.1007/s11064-013-1143-8

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