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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
Comparative anatomical assessment of the piglet as a model for the developing human medullary serotonergic system
Mary M Niblock1, Catherine J Luce, Richard A Belliveau
1Department of Physiology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756, USA. mary.niblock@dartmouth.edu
Insights
Piglets serve as a valuable model for human infant medullary serotonin (5-HT) system development. Despite minor differences in neuron distribution, the piglet
Area of Science:
- Neuroscience
- Developmental Biology
- Comparative Anatomy
Background:
- The piglet is a common model for studying human infant medullary serotonergic (5-HT) system development.
- Understanding species-specific 5-HT system development is crucial for accurate translational research.
Purpose of the Study:
- To compare the topographical distribution and developmental trajectories of 5-HT markers in human infants and piglets.
- To assess the validity of the piglet as a model for the human infant medullary 5-HT system.
Main Methods:
- Comparative analysis of tryptophan hydroxylase-immunoreactive 5-HT neuron topography in the medulla.
- Evaluation of age-related changes in 5-HT cell distribution and 5-HT receptor binding.
- Determination of equivalent postnatal developmental ages between species.
Main Results:
- Similar, though not identical, distribution of 5-HT neurons in the medulla of human infants and piglets.
- Distinctive ventral clusters of 5-HT neurons in piglets, with potentially homologous scattered neurons in human infants.
- Species-specific age-related changes: proportional cell distribution shifts in humans, receptor binding changes in piglets.
- Established equivalent developmental ages: e.g., piglet 4 days ≈ human 1 month; piglet 60 days ≈ human 12 months.
Conclusions:
- The piglet medulla exhibits significant similarities to the human infant medulla regarding 5-HT neuron topography.
- Identified species-specific developmental patterns in 5-HT system maturation.
- The data collectively support the use of the piglet as a relevant model for the human infant medullary 5-HT system, with consideration for species differences.
Abstract:
Because the piglet is frequently used as a model for developmental disorders of the medullary serotonergic (5-HT) system in the human infant, this review compares the topography and developmental profile of selected 5-HT markers between humans in the first year of life and piglets in the first 60 days of life. The distribution of tryptophan hydroxylase-immunoreactive 5-HT neurons in the human infant medulla is very similar, but not identical, to that in the piglet. One notable difference is the presence of compact clusters of 5-HT neurons at the ventral surface of the piglet medulla. While it lacks these distinctive clusters, the human infant medulla contains potentially homologous 5-HT neurons scattered along the ventral surface embedded in the arcuate nucleus. Each species shows evidence of age-related changes in the 5-HT system, but the changes are different in nature; in the human infant, statistically significant age-related changes are observed in the proportional distribution of medullary 5-HT cells, while in the piglet, statistically significant age-related changes are observed in the levels of 5-HT receptor binding in certain medullary nuclei. Analyses of 5-HT receptor binding profiles in selected nuclei in the two species suggest that the equivalent postnatal ages for 5-HT development in piglets and human infants are, respectively, 4 days and 1 month, 12 days and 4 months, 30 days and 6 months, and 60 days and 12 months. Collectively, when certain species differences are considered, these data support the use of the piglet as a model for the human infant medullary 5-HT system.
