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Prenatal protein deprivation in rats induces changes in prepulse inhibition and NMDA receptor binding
Abraham A Palmer1, David J Printz, Pamela D Butler
1Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA. aap2010@columbia.edu
Insights
Prenatal protein deprivation (PPD) in rats led to deficits in sensorimotor gating, a key schizophrenia symptom. This animal model shows potential for studying neurodevelopmental changes linked to schizophrenia.
Area of Science:
- Neuroscience
- Psychiatry
- Developmental Biology
Background:
- Epidemiological studies link prenatal malnutrition to increased schizophrenia risk.
- Prenatal protein deprivation (PPD) in animal models impacts adult brain function.
- Prepulse inhibition (PPI) deficits are observed in schizophrenia patients.
Purpose of the Study:
- To investigate the effects of PPD on prepulse inhibition (PPI) in rats.
- To examine changes in dopaminergic and glutaminergic receptor binding in PPD rats.
- To assess the utility of this PPD rat model for schizophrenia research.
Main Methods:
- Rat dams received normal or low-protein diets before and during pregnancy.
- Offspring were tested for PPI at postnatal days 35 and 56.
- Post-mortem analysis quantified NMDA and dopamine receptor binding in the striatum and hippocampus.
Main Results:
- Female rats exposed to PPD showed reduced PPI at postnatal day 56, indicating a sensorimotor gating deficit.
- Striatal NMDA receptor binding was elevated in PPD female rats.
- All PPD rats exhibited a decreased startle response (SR).
Conclusions:
- PPD induces age- and sex-dependent alterations in PPI and NMDA receptor binding in rats.
- These findings suggest PPD impacts sensorimotor gating and neurotransmitter systems relevant to schizophrenia.
- The PPD rat model offers a valuable tool for investigating schizophrenia's neurodevelopmental origins.
Abstract:
Epidemiological studies suggest that prenatal malnutrition increases the risk of developing schizophrenia. Animal models indicate that prenatal protein deprivation (PPD) affects many aspects of adult brain function. We tested the hypothesis that PPD in rats would alter prepulse inhibition (PPI), which is an operational measure of sensorimotor gating that is deficient in schizophrenia patients. Additionally, we examined dopaminergic and glutaminergic receptor binding in the striatum and hippocampus, which have been suggested to play a role in the etiology of schizophrenia. Rat dams were fed normal (25%) or low (6%) protein diets beginning 5 weeks prior to, and throughout pregnancy. The pups were tested at postnatal days (PND) 35 and 56 for PPI. Striatal and hippocampal NMDA receptor, and striatal dopamine receptor binding were quantified post-mortem in a subset of these rats. Female rats exposed to PPD had reduced levels of PPI at PND 56, but not PND 35, suggesting the emergence of a sensorimotor gating deficit in early adulthood. Striatal NMDA receptor binding was increased in PPD females. A decrease in initial startle response (SR) was also observed in all PPD rats relative to control rats. These results suggest that PPD causes age- and sex-dependent decreases in PPI and increases in NMDA receptor binding. This animal model may be useful for the investigation of neurodevelopmental changes that are associated with schizophrenia in humans.
