Perinatal Protein Restriction Induces Anhedonic-Like Behavior: Disturbed Hippocampal Neurotrophic Signaling and
María C Gutiérrez1,2, Ramiro G Comas Mutis1,2, María C Perondi1,2
1Departamento de Farmacología Otto Orsingher, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba (UNC), Córdoba, Argentina.
Insights
Early protein malnutrition in rats led to anhedonia, a depression symptom. This was linked to reduced brain-derived neurotrophic factor (BDNF) signaling and fewer dendritic spines in the hippocampus.
Area of Science:
- Neuroscience
- Developmental Biology
- Nutritional Psychiatry
Background:
- Early life nutrition significantly impacts brain development and function.
- Protein malnutrition during critical developmental periods can lead to lasting neurobiological changes.
- Anhedonia, a core symptom of depression, is associated with alterations in the brain's reward circuitry.
Purpose of the Study:
- To investigate the effects of maternal protein restriction on anhedonia in adult rats.
- To examine the role of hippocampal brain-derived neurotrophic factor (BDNF)-TrkB signaling in protein-restriction-induced anhedonia.
- To assess structural plasticity changes in the CA1 subregion of the dorsal hippocampus.
Main Methods:
- Adult rats exposed to protein restriction from gestation to postnatal day 30 (PR-rats) were compared to control rats.
- Sucrose preference test (SPT) was used to measure anhedonia.
- Levels of BDNF, phosphorylated TrkB (p-TrkB), and dendritic spine density in the dorsal hippocampus (DH) CA1 region were assessed.
Main Results:
- PR-rats exhibited significantly reduced sucrose preference, indicating anhedonia.
- Anhedonia in PR-rats correlated with decreased BDNF and p-TrkB levels in the DH.
- Reduced dendritic spine density, particularly mature spines (stubby and mushroom), was observed in CA1 pyramidal neurons of PR-rats.
Conclusions:
- Perinatal protein restriction contributes to anhedonia by impairing hippocampal BDNF-TrkB signaling.
- Structural remodeling, including reduced dendritic spine density in the CA1 region, may underlie the anhedonic phenotype.
- These findings highlight the long-term vulnerability to anhedonia resulting from early-life nutritional deficits.
Abstract:
Early protein malnutrition has been shown to affect the brain reward circuitry, leading to enduring molecular, neurochemical, and behavioral alterations. This study explored how maternal protein restriction contributes to anhedonia, a key depression symptom, focusing on the hippocampal BDNF-TrkB signaling and structural plasticity changes in the CA1 subregion of the dorsal hippocampus (DH). To achieve our goal, adult rats submitted to a protein restriction schedule from the 14th day of gestation up to 30 days of age (PR-rats) were subjected to the sucrose preference test (SPT) and compared with animals fed a normoprotein diet. Immediately after SPT, we assessed the levels of BDNF and its receptor TrkB and structural plasticity changes. Interestingly, PR-rats showed a significant decrease in sucrose preference. Furthermore, perinatal protein-restriction-induced anhedonia correlated with decreased BDNF and p-TrkB levels in the DH, alongside reduced dendritic spine density in CA1 pyramidal neurons, particularly mature spines (i.e., stubby and mushroom spines). These findings suggest that decreased hippocampal BDNF-TrkB signaling accompanied by structural remodeling in the CA1 pyramidal neurons may contribute to the reduced ability of undernourished animals to respond to rewarding stimuli, increasing their vulnerability to anhedonia later in life.
