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Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity AIDN: A Translational Neuroscience Approach
Published on: June 11, 2017
Respiratory viral infection in neonatal piglets causes marked microglia activation in the hippocampus and deficits in
Monica R P Elmore1, Michael D Burton, Matthew S Conrad
1Department of Animal Sciences, Integrative Immunology and Behavior Program, and Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, and Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana 47907.
Insights
Porcine reproductive and respiratory syndrome virus (PRRSV) infection in piglets activates brain microglia, causing neuroinflammation and spatial learning deficits. This highlights potential risks of respiratory infections to brain development in young mammals.
Area of Science:
- Neuroscience
- Immunology
- Developmental Biology
Background:
- Environmental factors impacting brain development are critical, especially in gyrencephalic species with significant perinatal growth.
- Peripheral infections during sensitive developmental periods can affect brain function, but data in humans and similar species are limited.
Purpose of the Study:
- To investigate the effects of porcine reproductive and respiratory syndrome virus (PRRSV) infection on hippocampal development and function in a piglet model.
- To assess neuroinflammation and cognitive performance following viral respiratory infection in young animals.
Main Methods:
- Postnatal day 7 piglets were inoculated with PRRSV.
- Microglial activation (MHC II expression) in the hippocampus was assessed at 13 and 20 days post-inoculation.
- Gene expression of inflammatory markers and neurotrophic factors was analyzed across brain regions.
- Spatial learning and memory were evaluated using a cognitive task.
Main Results:
- PRRSV infection led to significant microglial activation in the hippocampus (82% and 43% MHC II(+) at 13 and 20 days, respectively) compared to controls (<5%).
- Febrile conditions, anorexia, and reduced weight gain were observed in PRRSV-infected piglets.
- Increased expression of inflammatory genes (IL-1β, IL-6, TNF-α, IFN-γ) and decreased expression of CD200, NGF, and MBP were noted in multiple brain regions.
- PRRSV piglets exhibited impaired spatial learning, characterized by longer acquisition times, increased latency to choice, and greater distance moved.
Conclusions:
- Viral respiratory infection, exemplified by PRRSV, induces significant neuroinflammation, particularly microglial activation in the hippocampus.
- The infection resulted in measurable deficits in spatial cognitive function.
- Findings suggest that managing microglial activation may be crucial for mitigating the neurological consequences of respiratory infections in neonates and infants.
Abstract:
Environmental insults during sensitive periods can affect hippocampal development and function, but little is known about peripheral infection, especially in humans and other animals whose brain is gyrencephalic and experiences major perinatal growth. Using a piglet model, the present study showed that inoculation on postnatal day 7 with the porcine reproductive and respiratory syndrome virus (PRRSV) caused microglial activation within the hippocampus with 82% and 43% of isolated microglia being MHC II(+) 13 and 20 d after inoculation, respectively. In control piglets, <5% of microglia isolated from the hippocampus were MHC II(+). PRRSV piglets were febrile (p < 0.0001), anorectic (p < 0.0001), and weighed less at the end of the study (p = 0.002) compared with control piglets. Increased inflammatory gene expression (e.g., IL-1β, IL-6, TNF-α, and IFN-γ) was seen across multiple brain regions, including the hippocampus, whereas reductions in CD200, NGF, and MBP were evident. In a test of spatial learning, PRRSV piglets took longer to acquire the task, had a longer latency to choice, and had a higher total distance moved. Overall, these data demonstrate that viral respiratory infection is associated with a marked increase in activated microglia in the hippocampus, neuroinflammation, and impaired performance in a spatial cognitive task. As respiratory infections are common in human neonates and infants, approaches to regulate microglial cell activity are likely to be important.
