Fetal asphyxia leads to a decrease in dorsal raphe serotonergic neurons.

The aim of the present study was to determine the effects of fetal asphyxia (FA) on anxiety and serotonergic neurons in young adult and middle-aged rats. FA was induced at embryonic day 17 by clamping the uterine circulation for 75 min. Anxiety-related behavior was tested in an open field, and design-based stereology was used for counting serotonergic (5-hydroxytryptamine/serotonin, 5-HT) neurons in the dorsal raphe nucleus (DRN). The open field revealed increased anxiety in the 19-month-old FA rats in comparison to control animals. No significant differences were found in DRN 5-HT neuron numbers at 6 months. At 19 months, however, FA significantly lowered the mean density and volume of 5-HT neurons in the DRN as compared to controls. Further, an age-related reduction was found in the total number, the mean density and the mean volume of 5-HT neurons within the FA group. In conclusion, FA is associated with increased anxiety and age-related changes in 5-HT immunohistochemistry within the DRN. These results support the notion that insults caused by asphyxiation during critical periods of brain development could create a predisposition to serotonergic abnormalities and anxiety deficits in adulthood.