Related Experiment Video
Updated: Sep 30, 2026
Limited Bedding and Nesting as a Model for Early-Life Adversity in Mice
Published on: July 12, 2024
Early maternal deprivation reduces the expression of BDNF and NMDA receptor subunits in rat hippocampus
M Roceri1, W Hendriks, G Racagni
1Center of Neuropharmacology, Department of Pharmacological Sciences and Center of Excellence for Neurodegenerative Disorders, University of Milan, Milan, Italy.
Insights
Early life stress, like maternal separation (MD), can alter brain development. This study shows MD in rats reduces key proteins like brain-derived neurotrophic factor (BDNF) and NMDA receptors in adulthood, increasing psychiatric disorder vulnerability.
Area of Science:
- Neuroscience
- Developmental Psychology
- Molecular Psychiatry
Background:
- Events disrupting neuronal differentiation and brain maturation are implicated in psychiatric disorders.
- Synaptic disorganization during development may lead to later functional deficits.
Purpose of the Study:
- To investigate molecular changes in brain-derived neurotrophic factor (BDNF) and NMDA receptors following early life stress.
- To determine if maternal separation (MD) on postnatal day 9 affects these molecules in adulthood.
Main Methods:
- Maternal separation (MD) was performed on postnatal day 9 in rats.
- Expression of BDNF and NMDA receptor subunits (NR-2A, NR-2B) was analyzed in adulthood.
- Hippocampal BDNF response to acute stress was assessed in MD rats.
Main Results:
- Adult MD rats showed significantly reduced hippocampal expression of BDNF, NR-2A, and NR-2B.
- A slight reduction in NR-2A and NR-2B was observed in the prefrontal cortex.
- Changes were not present acutely or in pre-weaning animals.
- MD rats exhibited altered hippocampal BDNF modulation in response to acute stress.
Conclusions:
- Adverse early life events can permanently alter molecular expression related to plasticity in specific brain regions.
- These molecular changes may lead to lasting functional brain alterations and increased vulnerability to psychiatric diseases.
Abstract:
It is well accepted that events that interfere with the normal program of neuronal differentiation and brain maturation may be relevant for the etiology of psychiatric disorders, setting the stage for synaptic disorganization that becomes functional later in life. In order to investigate molecular determinants for these events, we examined the modulation of the neurotrophin brain-derived neurotrophic factor (BDNF) and the glutamate NMDA receptor following 24 h maternal separation (MD) on postnatal day 9. We found that in adulthood the expression of BDNF as well as of NR-2A and NR-2B, two NMDA receptor forming subunits, were significantly reduced in the hippocampus of MD rats whereas, among other structures, a slight reduction of NR-2A and 2B was detected only in prefrontal cortex. These changes were not observed acutely, nor in pre-weaning animals. Furthermore we found that in MD rats the modulation of hippocampal BDNF in response to an acute stress was altered, indicating a persistent functional impairment in its regulation, which may subserve a specific role for coping with challenging situations. We propose that adverse events taking place during brain maturation can modulate the expression of molecular players of cellular plasticity within selected brain regions, thus contributing to permanent alterations in brain function, which might ultimately lead to an increased vulnerability for psychiatric diseases.
