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Updated: Aug 15, 2026
Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats
Published on: December 14, 2014
Effect of chemically induced propionic acidemia on neurobehavioral development of rats
A M Brusque1, C F Mello, D N Buchanan
1Departmento de Bioquímica, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Insights
Early exposure to propionic acid (PPA) in rats, mimicking human propionic acidemia, caused developmental delays and long-term behavioral deficits. These findings highlight PPA
Area of Science:
- Developmental Neuroscience
- Metabolic Disorders
- Toxicology
Background:
- Propionic acidemia is a rare metabolic disorder with significant health implications.
- Understanding the effects of propionic acid (PPA) on early development is crucial for identifying potential therapeutic targets.
- This study investigates the impact of experimentally induced PPA levels on rat development and behavior.
Purpose of the Study:
- To establish a rat model with propionic acid levels comparable to human propionic acidemia.
- To assess the effects of early postnatal PPA administration on physical development, motor skills, and long-term behavior.
- To investigate the lasting neurological and behavioral consequences of PPA exposure during a critical developmental window.
Main Methods:
- Rats received subcutaneous injections of saline-buffered propionate from day 6 to 28 of life to achieve high blood and brain PPA levels.
- Physical development (body weight, incisor eruption, eye opening, hair coat) and motor skills (righting reflex, alternation test) were monitored.
- Long-term behavioral assessments included open-field and shuttle-avoidance tasks at 60 days of age.
Main Results:
- PPA administration resulted in slight delays in hair coat and eye opening but did not affect body or brain weight.
- Impaired free-fall righting reflex was observed, while spontaneous alternation performance remained unaffected.
- Long-term, PPA-treated rats showed impaired habituation in the open field and a lack of retention in the shuttle-avoidance task.
Conclusions:
- Early postnatal administration of propionic acid in rats alters normal physical development and induces significant long-term behavioral deficits.
- These deficits manifest in both aversive and non-aversive behavioral tasks, suggesting widespread neurological impact.
- The findings underscore the critical role of metabolic balance during early development and provide insights into propionic acidemia's potential neurological sequelae.
Abstract:
High levels of propionic acid (PPA) comparable to those of human propionic acidemia were achieved in blood (1-5 mmol/l) and brain (1 micromol/g) of rats by administering saline-buffered propionate (pH 7.4) subcutaneously twice a day from the 6th to the 28th day of life. PPA doses ranged from 1.44 to 1.92 micromol/g body weight as a function of animal age. Control rats were treated with saline in the same volumes. Growth and development of physical landmarks were assessed by monitoring the following parameters daily: body weight, upper incisor eruption, eye opening, and hair coat. Development of some reflexes was also monitored, and a specific subset of motor skills was evaluated at days 14 and 21 of life by the free-fall righting test and the spontaneous alternation test. Chronic PPA administration had no effect on body weight, cerebral cortex weight, or cerebellum weight, but caused slight but significant delays in the day of appearance of hair coat and eye opening, indicating an effect of PPA on the development of physical parameters. Free-fall righting was impaired in PPA-treated animals. On the other hand, PPA administration had no effect on the performance of the animals in the spontaneous alternation tests. Long-term effects of early PPA administration were investigated by assessing animal performance in an aversive task (two-way shuttle avoidance task) and in a nonaversive (open-field task) behavioral task at 60 days of age. PPA-treated rats did not habituate to the open field, and presented a lack of retention of the shuttle-avoidance task. Our results suggest that early postnatal PPA administration to rats alters normal development and induces long-term behavioral deficits in aversive and nonaversive tasks.
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