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Slow Physical Growth, Delayed Reflex Ontogeny, and Permanent Behavioral as Well as Cognitive Impairments in Rats
Aijaz A Naik1, Ishan K Patro1, Nisha Patro2
1School of Studies in Neuroscience, Jiwaji University Gwalior, India ; School of Studies in Zoology, Jiwaji University Gwalior, India.
Insights
Maternal protein malnutrition during gestation and early life impacts offspring neurodevelopment, leading to cognitive deficits and Alzheimer
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Science
Background:
- Maternal protein malnutrition (PMN) during critical developmental windows affects cognitive function and increases neuropsychiatric disorder risk.
- Existing research often examines limited periods, failing to capture the full impact of malnutrition across generations, unlike clinical conditions like intra-uterine growth restriction (IUGR).
- This study introduces a novel intra-generational model of PMN, examining effects from gestation through the F1 generation.
Purpose of the Study:
- To investigate the sex-specific neurobehavioral development and behavioral phenotype in the F1 generation following maternal protein restriction.
- To establish a comprehensive model of PMN effects spanning gestation to offspring adulthood.
Main Methods:
- Sprague Dawley dams were fed either a low-protein (LP, 8%) or high-protein (HP, 20%) diet pre-gestationally and throughout gestation.
- Offspring (F1 generation) were maintained on the respective maternal diets post-weaning.
- A battery of tests assessed neurodevelopmental reflexes, open field behavior, grip strength, and cognitive functions (Elevated Plus Maze, Morris Water Maze).
Main Results:
- LP offspring exhibited decelerated growth, reduced body and brain weight, delayed neuro-reflexes, and impaired performance.
- Intra-generational PMN resulted in poor habituation, reduced anxiety, hyperactivity, and diminished forelimb neuromuscular strength in LP offspring.
- Cognitive assays revealed hyperactivity, poor learning, impaired memory retention, and signs of early-onset Alzheimer's phenotype, with greater severity in males.
Conclusions:
- Maternal protein malnutrition from gestation onward significantly impacts F1 generation neurodevelopment and behavior, creating an Alzheimer's-like phenotype.
- The study highlights sex-specific effects, with males showing more severe consequences of protein restriction.
- This research provides a comprehensive model for understanding the long-term neurobehavioral consequences of early-life nutritional stress.
Abstract:
Environmental stressors including protein malnutrition (PMN) during pre-, neo- and post-natal age have been documented to affect cognitive development and cause increased susceptibility to neuropsychiatric disorders. Most studies have addressed either of the three windows and that does not emulate the clinical conditions of intra-uterine growth restriction (IUGR). Such data fail to provide a complete picture of the behavioral alterations in the F1 generation. The present study thus addresses the larger window from gestation to F1 generation, a new model of intra-generational PMN. Naive Sprague Dawley (SD) dams pre-gestationally switched to LP (8% protein) or HP (20% protein) diets for 45 days were bred and maintained throughout gestation on same diets. Pups born (HP/LP dams) were maintained on the respective diets post-weaningly. The present study aimed to show the sex specific differences in the neurobehavioral evolution and behavioral phenotype of the HP/LP F1 generation pups. A battery of neurodevelopmental reflex tests, behavioral (Open field and forelimb gripstrength test), and cognitive [Elevated plus maze (EPM) and Morris water maze (MWM)] assays were performed. A decelerated growth curve with significantly restricted body and brain weight, delays in apparition of neuro-reflexes and poor performance in the LP group rats was recorded. Intra-generational PMN induced poor habituation-with-time in novel environment exploration, low anxiety and hyperactive like profile in open field test in young and adult rats. The study revealed poor forelimb neuromuscular strength in LP F1 pups till adulthood. Group occupancy plots in MWM test revealed hyperactivity with poor learning, impaired memory retention and integration, thus modeling the signs of early onset Alzehemier phenotype. In addition, a gender specific effect of LP diet with severity in males and favoring female sex was also noticed.
