Allopregnanolone infusion induced neurobehavioural alterations in a neonatal foal: is this a clue to the pathogenesis of neonatal maladjustment syndrome?
Abstract: Increased plasma progestagen concentrations have been reported in foals with neonatal maladjustment syndrome (NMS). These steroids may cross the blood-brain barrier and have dampening effects in the central nervous system. Objective: To evaluate if the infusion of a progesterone derivative (allopregnanolone) in a healthy neonatal foal would induce clinical signs compatible with NMS. Methods: A healthy neonatal foal from a healthy mare with a normal gestation (length, no complications), birth and placenta was infused with allopregnanolone to observe its neurobehavioural effects. Heparinised blood samples were collected pre- and post infusion to determine various progestagen concentrations using liquid chromatography mass spectrometry. A second healthy neonatal foal was infused with ethanol and saline for comparison of clinical observations. Results: Infusion of allopregnanolone resulted in obtundation, lack of affinity for the mare and decreased response to external stimuli. These effects were short-lasting and associated with measurable concentrations of progestagens. Conclusions: Infusion of a steroid metabolite to a healthy neonatal foal resulted in neurobehavioural alterations compatible with those observed in foals with NMS. These findings suggest that increased progestagen concentrations may be responsible for some of the behavioural changes observed in foals with NMS.
Publication Date: 2012-05-19 PubMed ID: 22594038DOI: 10.1111/j.2042-3306.2011.00504.xGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study investigates if the hormone progesterone, specifically its derivative allopregnanolone, could be responsible for some of the behavioural changes seen in foals suffering from neonatal maladjustment syndrome (NMS). Infusion of allopregnanolone in a healthy newborn foal resulted in symptoms similar to NMS, suggesting that high levels of progesterone could be a contributing factor to the condition.
Objective and Method
- The research was undertaken to understand if the infusion of a progesterone derivative, specifically allopregnanolone, in a healthy newborn horse, could produce clinical signs similar to Neonatal Maladjustment Syndrome (NMS).
- To establish this connection, a healthy newborn horse, birthed from a healthy mare with a normal gestation period and no birth or placental complications, was infused with allopregnanolone.
- The neurological and behavioural effects of this infusion were then observed and documented.
- Blood samples from the foal were taken prior to and after the hormone infusion to ascertain different progestogen concentrations. This was done using liquid chromatography mass spectrometry, a process to identify individual chemicals and substances in a sample.
- For comparison, a second healthy newborn horse was infused with ethanol and saline. The clinical observations from both cases were then evaluated agaisnt each other.
Results
- The infusion of allopregnanolone in the first foal led to several changes in its behaviour, signalling possible signs of NMS. These included lack of energy (obtundation), reduced interest in its mother (lack of affinity for the mare) and a decreased response to external stimuli.
- These behavioural changes were temporary and were noted at the time of measurable concentrations of progestagens, hormones derived from progesterone.
Conclusions
- The behavioural changes observed post infusion mirrored the symptoms seen in foals afflicted with NMS, suggesting a connection between the two.
- The research indicates that an increase in progestagen concentrations could be a contributing factor for some of the behavioural changes observed in foals suffering from NMS.
Cite This Article
APA
Madigan JE, Haggettt EF, Pickles KJ, Conley A, Stanley S, Moeller B, Toth B, Aleman M.
(2012).
Allopregnanolone infusion induced neurobehavioural alterations in a neonatal foal: is this a clue to the pathogenesis of neonatal maladjustment syndrome?
Equine Vet J Suppl(41), 109-112.
https://doi.org/10.1111/j.2042-3306.2011.00504.x Publication
Researcher Affiliations
- Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, USA.
MeSH Terms
- Animals
- Animals, Newborn
- Central Nervous System Diseases / veterinary
- Horse Diseases / chemically induced
- Horses
- Male
- Pregnanolone / administration & dosage
- Pregnanolone / toxicity
- Syndrome
Citations
This article has been cited 10 times.- Ellero N, Lanci A, Mariella J, van den Boom R, Cotticelli A, Peric T, Prandi A, Freccero F, Castagnetti C. Hair Allopregnanolone in Mares and Foals as a Retrospective Biomarker of Predicting Feto-Maternal Well-Being. Animals (Basel) 2025 Mar 7;15(6).
- Porto ACRC, Redoan MA, Massoco CO, Furtado PV, Oliveira CA. Additional effects using progestins in mares on levels of thyroid hormones and steroids in neonates. Anim Reprod 2023;20(4):e20230029.
- Peric T, Ellero L, Comin A, Pividori I, Prandi A. Validation of an ELISA kit to measure allopregnanolone in human and equine hair. J Vet Diagn Invest 2023 Jul;35(4):354-358.
- Ellero N, Lanci A, Baldassarro VA, Alastra G, Mariella J, Cescatti M, Castagnetti C, Giardino L. Study on NGF and VEGF during the Equine Perinatal Period-Part 2: Foals Affected by Neonatal Encephalopathy. Vet Sci 2022 Aug 26;9(9).
- Swink JM, Rings LM, Snyder HA, McAuley RC, Burns TA, Dembek KA, Gilsenan WF, Browne N, Toribio RE. Dynamics of androgens in healthy and hospitalized newborn foals. J Vet Intern Med 2021 Jan;35(1):538-549.
- Aleman M, Chigerwe M, Varga A, Madigan JE. Steroid precursors, steroids, neuroactive steroids, and neurosteroids concentrations in serum and saliva of healthy neonatal heifer Holstein calves. J Vet Intern Med 2020 Nov;34(6):2767-2775.
- Aleman M, McCue PM, Chigerwe M, Madigan JE. Plasma concentrations of steroid precursors, steroids, neuroactive steroids, and neurosteroids in healthy neonatal foals from birth to 7 days of age. J Vet Intern Med 2019 Sep;33(5):2286-2293.
- Aleman M, Weich KM, Madigan JE. Survey of Veterinarians Using a Novel Physical Compression Squeeze Procedure in the Management of Neonatal Maladjustment Syndrome in Foals. Animals (Basel) 2017 Sep 5;7(9).
- Bianco AW, Moore GE, Taylor SD. Neonatal Encephalopathy in Calves Presented to a University Hospital. J Vet Intern Med 2017 Nov;31(6):1892-1899.
- McCallie KR, Gaikwad NW, Castillo Cuadrado ME, Aleman M, Madigan JE, Stevenson DK, Bhutani VK. Skin-to-skin contact after birth and the natural course of neurosteroid levels in healthy term newborns. J Perinatol 2017 May;37(5):591-595.
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