Perinatal asphyxia exerts lifelong effects on neuronal responsiveness to stress in specific brain regions in the rat.
BACKGROUND
Perinatal asphyxia (PA) causes irreversible damage to the brain of newborns and can produce neurologic and behavioral changes later in life. To identify neuronal substrates underlying the effects of PA, we investigated whether and how neuronal responsiveness to an established stress challenge is affected.


METHODS
We used Fos expression as a marker of neuronal activation and examined the pattern of Fos expression in response to acute swim stress in 24-month-old rats exposed to a 20-minute PA insult.


RESULTS
Swim stress produced a similar pattern of Fos expression in control and asphyxiated rats in 34 brain areas. Asphyxiated rats displayed a higher number of stress-induced Fos-positive cells in the nucleus of the solitary tract, parabrachial nucleus, periaqueductal gray, paraventricular hypothalamic nucleus, nucleus accumbens, caudate-putamen, and prelimbic cortex. No differences in the Fos response to stress were observed in other regions, including the locus ceruleus, amygdala, hippocampus, or septum.


CONCLUSIONS
These data provide functional anatomic evidence that PA has lifelong effects on neuronal communication and leads to an abnormal, augmented neuronal responsiveness to stress in specific brain areas, particularly in the main telencephalic target regions of the mesencephalic dopamine projections, as well as in a functionally related set of brain regions associated with autonomic and neuroendocrine regulation.
Department of Pharmacology and Toxicology, University of Innsbruck, Innsbruck, Austria.
Peter
P
Salchner
Ephrem
E
Engidawork
Harald
H
Hoeger
Barbara
B
Lubec
Nicolas
N
Singewald
D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D002534:Hypoxia, Brain / Q000378:metabolism*; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013312:Stress, Physiological / Q000378:metabolism*; D013550:Swimming
D015415:Biomarkers; D016760:Proto-Oncogene Proteins c-fos