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Published on: December 4, 2013
Cognitive performance during adulthood in a rat model of neonatal diffuse white matter injury
E J Marijke Achterberg1, Ralf J van Oldeniel2,3, Erik van Tilborg3
1Department of Population Health Sciences, Unit Animals in Science and Society, Division of Behavioural Neuroscience, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584CM, Utrecht, The Netherlands. e.j.m.achterberg@uu.nl.
Insights
This study found that a rat model of preterm white matter injury (WMI) did not result in lasting cognitive deficits. While some subtle behavioral differences were noted, the model did not fully replicate the long-term cognitive impairments seen in human infants.
Area of Science:
- Neuroscience
- Developmental Biology
- Pediatrics
Background:
- Preterm infants face risks of diffuse white matter injury (WMI), linked to cognitive impairments and autism spectrum disorder.
- A rat model of preterm WMI (fetal inflammation + postnatal hypoxia) exhibited motor, anxiety, and autism-like behaviors, with delayed myelination in juveniles.
- Oligodendrocyte differentiation was impaired in the sensory cortex of juvenile rats with WMI.
Purpose of the Study:
- To evaluate long-term cognitive deficits in a double-hit rat model of diffuse white matter injury (WMI).
- Assessed impulsivity, attention, and cognitive flexibility in adulthood using the 5-choice serial reaction time task (5CSRTT) and probabilistic reversal learning task.
- Investigated persistent myelination deficits via immunofluorescent staining in adulthood.
Main Methods:
- Utilized a rat model of preterm diffuse white matter injury (WMI).
- Administered adult cognitive assessments including the 5-choice serial reaction time task (5CSRTT) and a probabilistic reversal learning task.
- Conducted immunofluorescent staining to evaluate myelination in adolescence and adulthood.
Main Results:
- Minimal cognitive effects of WMI or sex were observed in the 5CSRTT and reversal learning tasks.
- Subtle performance differences in the 5CSRTT were noted in WMI animals.
- Sex differences emerged: female WMI rats showed less flexibility in 5CSRTT, while males were faster in the reversal learning task.
Conclusions:
- The rat model of preterm WMI did not induce significant long-term cognitive deficits.
- Findings suggest temporally affected myelination and limited prefrontal cortex injury contribute to the observed results.
- This model does not fully recapitulate the persistent cognitive impairments seen in prematurely born human infants.
Rationale:
Infants born prematurely risk developing diffuse white matter injury (WMI), which is associated with impaired cognitive functioning and an increased risk of autism spectrum disorder. Recently, our rat model of preterm diffuse WMI induced by combined fetal inflammation and postnatal hypoxia showed impaired motor performance, anxiety-like behaviour and autism-like behaviour in juvenile rats, especially males. Immunohistochemistry showed delayed myelination in the sensory cortex and impaired oligodendrocyte differentiation.
Objective:
To assess long-term cognitive deficits in this double-hit rat model of diffuse WMI, animals were screened on impulsivity, attention and cognitive flexibility in adulthood using the 5-choice serial reaction time task (5CSRTT) and a probabilistic reversal learning task, tests that require a proper functioning prefrontal cortex. Thereafter, myelination deficits were evaluated by immunofluorescent staining in adulthood.
Results:
Overall, little effect of WMI or sex was found in the cognitive tasks. WMI animals showed subtle differences in performance in the 5CSRTT. Manipulating 5CSRTT parameters resulted in performance patterns previously seen in the literature. Sex differences were found in perseverative responses and omitted trials: female WMI rats seem to be less flexible in the 5CSRTT but not in the reversal learning task. Males collected rewards faster in the probabilistic reversal learning task. These findings are explained by temporally rather than permanently affected myelination and by the absence of extensive injury to prefrontal cortical subregions, confirmed by immunofluorescent staining in both adolescence and adulthood.
Conclusion:
This rat model of preterm WMI does not lead to long-term cognitive deficits as observed in prematurely born human infants.
