Long-term sequelae of perinatal asphyxia in the aging rat

Weitzdoerfer, Rachel; Gerstl, N.; Hoeger, Harald; Mosgoeller, Wilhelm; Dreher, Wolfgang; Engidawork, Ephrem; Overgaard-Larsen, J.; Lubec, Barbara

doi:10.1007/s00018-002-8443-5

Cited by 15 publications

(15 citation statements)

References 15 publications

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“…increased anxiety in senescent rats at the age of 18 months was found by Weitzdoerfer et al . (2002). Moreover, there is a relationship between early exposure and increased risk for neurodegenerative and other diseases at higher age (long-term and/or delayed effects).…”

Section: Most Important Issues To Be Taken Into Account In Neurobehavmentioning

confidence: 99%

Evaluation of developmental neurotoxicity: some important issues focused on neurobehavioral development

Dubovický¹,

P²,

Ujházy³

et al. 2008

Interdisciplinary Toxicology

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Exposure of the developing organism to industrial chemicals and physical factors represents a serious risk factor for the development of neurobehavioral disorders, such as attention-deficit hyperactivity disorder, autism and mental retardation. Appropriate animal models are needed to test potentially harmful effects and mechanisms of developmental neurotoxicity of various chemical substances. However, there are significant human vs. rat differences in the brain developmental profile which should be taken into account in neurotoxicity studies. Subtle behavioral alterations are hard to detect by traditional developmental toxicity and teratogenicity studies, and in many cases they remain hidden. They can however be revealed by using special behavioral, endocrine and/or pharmacological challenges, such as repeated behavioral testing, exposure to single stressful stimulus or drugs. Further, current neurobehavioral test protocols recommend to test animals up to their adulthood. However some behavioral alterations, such as anxiety-like behavior or mental deficiency, may become manifest in later periods of development. Our experimental and scientific experiences are highly suggestive for a complex approach in testing potential developmental neurotoxicity. Strong emphasis should be given on repeated behavioral testing of animals up to senescence and on using proper pharmacological and/or stressful challenges.

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Section: Most Important Issues To Be Taken Into Account In Neurobehavmentioning

confidence: 99%

Evaluation of developmental neurotoxicity: some important issues focused on neurobehavioral development

Dubovický¹,

P²,

Ujházy³

et al. 2008

Interdisciplinary Toxicology

View full text Add to dashboard Cite

show abstract

“…Our recent study [9] on cognitive functions performed in aged rats with PA showed a significant impairment in relearning together with an abnormal serotoninergic transport system. We, therefore, aimed at evaluating whether PA affects also anxiety-related and social behaviors in rats at the end of their life span, performing open-field test, elevated plusmaze test, a social interaction test, as well as magnetic resonance imaging studies in 2-year-old rats which suffered PA.…”

Section: Introductionmentioning

confidence: 99%

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

Weitzdoerfer

Gerstl²,

Pollak³

et al. 2004

Gerontology

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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.

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“…An increase in intracellular 5-HT content can be caused by different mechanisms, such as an enhanced synthesis, a decreased degeneration or a changed reuptake capacity of 5-HT. An increased reuptake was already demonstrated by Weitzdoerfer et al [13] . They showed increased serotonin transporter (5-HTT) levels in the hippocampus of 2-year-old rats exposed to perinatal asphyxia.…”

Section: Fa Causes An Age-related Decline In the Total Number Densitmentioning

confidence: 52%

“…Previous research in our group showed impaired memory performance in 18-month-old perinatal asphyxiated rats compared to control animals [12] . Likewise, Weitzdoerfer et al [13] demonstrated lower cognitive function in 2-year-old perinatal asphyxiated rats. These changes were associated with higher hippocampal levels of the serotonin (5-hydroxytryptamine, 5-HT) transporter.…”

mentioning

confidence: 99%

Fetal Asphyxia Leads to a Decrease in Dorsal Raphe Serotonergic Neurons

Strackx¹,

Hove

Steinbusch

et al. 2008

Dev Neurosci

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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.

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Long-term sequelae of perinatal asphyxia in the aging rat

Cited by 15 publications

References 15 publications

Evaluation of developmental neurotoxicity: some important issues focused on neurobehavioral development

Evaluation of developmental neurotoxicity: some important issues focused on neurobehavioral development

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

Fetal Asphyxia Leads to a Decrease in Dorsal Raphe Serotonergic Neurons

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