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The Journal of Neuroscience, June 27, 2007, 27(26):7041-7046; doi:10.1523/JNEUROSCI.1074-07.2007

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Development/Plasticity/Repair
Maternal Exposure to Low Levels of Corticosterone during Lactation Protects the Adult Offspring against Ischemic Brain Damage

Paola Casolini,¹ Maria Rosaria Domenici,² Carlo Cinque,¹ Giovanni Sebastiano Alemà,¹ Valentina Chiodi,¹ Mariangela Galluzzo,² Marco Musumeci,² Jerome Mairesse,³ Anna Rita Zuena,¹ Patrizia Matteucci,¹ Giuseppe Marano,² Stefania Maccari,^3,5 Ferdinando Nicoletti,^1,4 and Assia Catalani¹

¹Department of Human Physiology and Pharmacology, University of Rome "La Sapienza," Faculty of Medicine, 00185 Rome, Italy, ²Department of Pharmacology, Istituto Superiore di Sanità, 00161 Rome, Italy, ³Laboratory of Perinatal Stress, University of Lille 1, 59655 Villeneuve d'Ascq, France, ⁴Istituto Neurologico Mediterraneo, Neuromed Pozzilli, 86077 Pozzilli, Italy, and ⁵University of Rome "La Sapienza," Faculty of Medicine, 00185 Rome, Italy

Correspondence should be addressed to Assia Catalani, Department of Human Physiology and Pharmacology, University of Rome "La Sapienza," Piazzale Aldo Moro 5, 00185 Rome, Italy. Email: assia.catalani{at}uniroma1.it

A growing body of evidence underscores the importance of early life events as predictors of health in adulthood. Abnormalities in maternal care or other forms of early postnatal stress induce long-term changes in behavior and influence the vulnerability to illnesses throughout life. Some of these changes may be produced by the activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is invariably associated with stress. We used a model in which neonate rats are fed by mothers drinking water supplemented with 0.2 mg/ml corticosterone, the main glucocorticoid hormone in rodents. Plasma corticosterone levels increased in the dams to an extent similar to that induced by a mild stress. Corticosterone-treated dams also showed an increase in maternal care. Remarkably, adult rats that had been nursed by corticosterone-treated mothers were protected against neuronal damage and cognitive impairment produced by transient global brain ischemia. Neuroprotection was associated with a reduced HPA response to ischemia and was primarily decreased when corticosterone was injected at a dose that eliminated any difference in endogenous corticosterone levels between rats raised by mothers supplemented with corticosterone and their matched controls. These data suggest that an increased maternal care protects the offspring against ischemic neuronal damage and that at least a component of neuroprotection is mediated by a reduced response of the HPA axis to ischemia.

Key words: corticosteroids; early events in life; brain damage; neuronal vulnerability; ischemia; stress

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Received Aug. 9, 2006; revised May 17, 2007; accepted May 22, 2007.

Correspondence should be addressed to Assia Catalani, Department of Human Physiology and Pharmacology, University of Rome "La Sapienza," Piazzale Aldo Moro 5, 00185 Rome, Italy. Email: assia.catalani{at}uniroma1.it

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