Prenatal stress elicits regionally selective changes in basal FGF-2 gene expression in adulthood and alters the adult response to acute or chronic stress.
Exposure to stress during pregnancy influences the trajectory of brain development resulting in permanent alterations that may contribute to increased susceptibility to subsequent cognitive or neuropsychiatric disorders. In this manuscript, we examined the effects of prenatal stress on the expression of basic fibroblast growth factor (FGF-2), an important molecular regulator of development and plasticity, in adult male rats under basal conditions as well as in response to acute or chronic stress. Baseline FGF-2 mRNA levels were differentially influenced by gestational stress in a variety of brain regions, with significant decreases in prefrontal cortex and increases in entorhinal cortex and striatum. By itself, postnatal stress similarly decreased trophic factor expression in prefrontal cortex while evoking stimulation elsewhere. Gestational stress altered the pattern of FGF-2 expression in response to adult stress, completely reversing the pattern in the prefrontal cortex (stimulatory instead of inhibitory), blunting the response in the entorhinal cortex and desensitizing the response in the striatum. These effects point to a unique interference of chronic prenatal stress with both ongoing FGF-2 expression and its responses to subsequent stressors, lasting into adulthood. Given the multifaceted role of FGF-2 in synaptic development, maintenance and plasticity, these data provide detailed mechanistic evidence as to how prenatal stress elicits lifelong effects on synaptic function. The abnormal modulation of FGF-2 gene expression in specific brain regions in response to subsequent stress in adulthood may impair the normal adaptive responses of the cell to challenging situations.
Fumagalli
Fabio
F
Center of Neuropharmacology, Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases (CEND), University of Milan, Via Balzaretti 9, 20133 Milan, Italy.
Bedogni
Francesco
F
Slotkin
Theodore A
TA
Racagni
Giorgio
G
Riva
Marco Andrea
MA
D000208:Acute Disease; D000222:Adaptation, Physiological / Q000235:genetics; D000223:Adaptation, Psychological / Q000502:physiology; D000375:Aging / Q000235:genetics; D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000378:metabolism* / Q000503:physiopathology; D002908:Chronic Disease; D003342:Corpus Striatum / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000235:genetics; D018728:Entorhinal Cortex / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D008297:Male; D019965:Neurocognitive Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000235:genetics*; D017397:Prefrontal Cortex / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation / Q000235:genetics
D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2