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Effects of postnatal methylmalonate administration on neurobehavioral development of rats
C F Mello1, J E Somer, V Tavaroni
1Departamento de Química, Universidade Federal de Santa Maria, Brasil.
Abstract:
Administration of methylmalonic acid in rats has been used as a model for methylmalonicacidemia in humans. Nestling Wistar rats of both sexes received 5 injections daily at 3-h intervals (starting at 7:30 a.m.) of saline or methylmalonic acid (MMA, 10 mg/ml) in a volume of 9 microliters/g body weight per injection subcutaneously in the lumbar region from the 5th to the 9th day of life and 11 microliters/g from day 10 to 14. Growth and neuromotor development were assessed by monitoring the following parameters daily in 54 rats: body weight, ear unfolding, incisor eruption, eye opening, righting, palmar grasp, negative geotaxis, cliff avoidance, free-fall righting and startle reflex. The only statistically significant effects of MMA administration were on the day of appearance of the free-fall righting reflex: MMA, 12.44 +/- 1.55 vs 11.0 +/- 0.39 days for saline control (P < 0.05, by two-way ANOVA) and a significant decrease in weight (P < 0.05, by ANOVA with repeated measures). The results suggest that chronic MMA administration to rats has a selective effect on neuromotor development.
Insights
Methylmalonic acid (MMA) administration in rats models human methylmalonic acidemia. Chronic MMA exposure selectively delayed free-fall righting reflex development and decreased weight in developing rats.
Area of Science:
- Biomedical Research
- Developmental Neuroscience
- Toxicology
Background:
- Methylmalonic acidemia is a human metabolic disorder.
- Animal models are crucial for studying metabolic diseases and their developmental impacts.
- Rats are frequently used to model human developmental processes.
Purpose of the Study:
- To investigate the effects of chronic methylmalonic acid administration on neuromotor development in Wistar rats.
- To establish a rat model for methylmalonic acidemia and assess its impact on growth and development.
Main Methods:
- Nestling Wistar rats received daily subcutaneous injections of methylmalonic acid (MMA) or saline from day 5 to 14 of life.
- Growth parameters (body weight) and neuromotor reflexes (ear unfolding, incisor eruption, eye opening, righting, palmar grasp, negative geotaxis, cliff avoidance, free-fall righting, startle reflex) were monitored daily.
- Statistical analysis included two-way ANOVA and ANOVA with repeated measures.
Main Results:
- Chronic MMA administration resulted in a statistically significant delay in the appearance of the free-fall righting reflex (12.44 days for MMA vs. 11.0 days for control, P < 0.05).
- A significant decrease in body weight was observed in the MMA-treated group compared to controls (P < 0.05).
- Other assessed neuromotor parameters and growth indicators did not show statistically significant differences.
Conclusions:
- Chronic administration of methylmalonic acid in rats selectively impacts neuromotor development, specifically delaying the free-fall righting reflex.
- This rat model demonstrates potential for studying the neurological consequences of methylmalonic acidemia.
- Further research is warranted to explore the specific mechanisms underlying MMA's neurodevelopmental effects.