Maternal exposure to low levels of corticosterone during lactation protects the adult offspring against ischemic brain damage.
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.
Casolini
Paola
P
Department of Human Physiology and Pharmacology, University of Rome La Sapienza, Faculty of Medicine, 00185 Rome, Italy.
Domenici
Maria Rosaria
MR
Cinque
Carlo
C
Alemà
Giovanni Sebastiano
GS
Chiodi
Valentina
V
Galluzzo
Mariangela
M
Musumeci
Marco
M
Mairesse
Jerome
J
Zuena
Anna Rita
AR
Matteucci
Patrizia
P
Marano
Giuseppe
G
Maccari
Stefania
S
Nicoletti
Ferdinando
F
Catalani
Assia
A
D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D003345:Corticosterone / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D007774:Lactation / Q000502:physiology*; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000378:metabolism / Q000503:physiopathology; D013995:Time
D018696:Neuroprotective Agents; D003345:Corticosterone