Long-Term Influence of Perinatal Asphyxia on the Social Behavior in Aging Rats

Abstract

Background: Various groups have been addressing the question of whether perinatal asphyxia (PA) affects the behavior of young animals, but no information is available on long-term effects of PA on the behavior in aged rats, although it has been postulated that PA may lead to neurological and psychiatric deficits in adult life. Objective: We, therefore, decided to study the effects of PA on social and anxiety-related behaviors in 2-year-old rats, using a noninvasive animal model resembling the clinical situation. Methods: For the behavioral studies, the open-field test, the elevated plus-maze test, and a social interaction test in pairs were performed. Magnetic resonance imaging of the brain was selected to rule out neuropathological changes due to the aging process per se, as well as asphyxia-induced pathologies in the brain areas known to play an important role in the modulation of behavior. Results: The social interaction test revealed a statistically significant increase in the number of social grooming episodes and the time spent running alone, whereas the numbers of social sniffing and fighting episodes and the time spent running together were decreased in the asphyxiated group. The elevated plus- maze test revealed a higher presence of entries into the closed arm. Furthermore, sniffing and self-grooming episodes were significantly increased in the asphyxiated group. Conclusions: We found a significantly decreased social aggressiveness and an increased social contact behavior as well as increased anxiety levels in the asphyxiated animals. The present findings may provide important information on the long-term behavioral sequelae of PA in the aged individual.

Fetal Asphyxia Leads to a Decrease in Dorsal Raphe Serotonergic Neurons

“…These observations point towards higher levels of anxiety in comparison to control animals. These results are in line with a previous report of Weitzdoerfer et al [14] , who showed an increase in anxiety-related behavior in 2-year-old rats exposed to perinatal asphyxia.…”

“…These changes were associated with higher hippocampal levels of the serotonin (5-hydroxytryptamine, 5-HT) transporter. The same group also found increased anxiety levels in the same perinatal animal model [14] . Cai et al [15] reported an altered hippocampal nitric oxide synthase system and learning deficits in young rats previously subjected to fetal asphyxia (FA).…”

“…The link between term perinatal asphyxia and an accelerated vulnerability of dopaminergic neurons has already been suggested by Loidl et al [9] . Similarly, Weitzdoerfer et al [14] postulated that age-related behavioral changes, like aggressive behavior and decreased social exploration, are intensified after perinatal asphyxia. Additionally, it is interesting to note that Nyakas et al [45] found anatomical abnormalities in the serotonergic fibers of 28-month-old rats after perinatal nitrite exposure.…”

Coronin proteins as multifunctional regulators of the cytoskeleton and membrane trafficking

“…Clinical investigations have revealed that coronin 1 and the Arp2/3 complex 20 kDa subunit are downregulated in the fetal Down syndrome brain cortex. (48) Both are proteins apparently involved in the dysgenesis of the brain and the associated mental disabilities. In murine brain all areas express coronin 3 during embryogenesis and the first postnatal stages.…”

Neurobehavioral manifestations of developmental impairment of the brain

“…Asphyxiated animals in the perinatal period were found to exhibit a significantly decreased social aggressiveness and an increased social contact behavior, as well as increased anxiety levels in adulthood (Weitzdoerfer et al ., 2004). Antenatal intermittent hypoxia caused a decrease of motor activity as well as an enhanced anxiety level in rats of both sexes, while males appeared to be more sensitive to hypoxic influence (Trofinmova et al ., 2010).…”