Early Life Stress Combined with Serotonin 3A Receptor and Brain-Derived Neurotrophic Factor Valine 66 to Methionine Genotypes Impacts Emotional Brain and Arousal Correlates of Risk for Depression

Early life adversity increases the risk of mental disorders later in life. Chronic early life stress may alter neurotrophic factor gene expression including those for brain derived neurotrophic factor (BDNF) and glial cell derived neurotrophic factor (GDNF) that are important in neuronal growth, survival, and maintenance. Maternal separation was used in this study to model early life stress. Following unilateral injection of a mild dose of 6-hydroxydopamine (6-OHDA), we measured corticosterone (CORT) in the blood and striatum of stressed and nonstressed rats; we also measured DNA methylation and BDNF and GDNF gene expression in the striatum using real time PCR. In the presence of stress, we found that there was increased corticosterone concentration in both blood and striatal tissue. Further to this, we found higher DNA methylation and decreased neurotrophic factor gene expression. 6-OHDA lesion increased neurotrophic factor gene expression in both stressed and nonstressed rats but this increase was higher in the nonstressed rats. Our results suggest that exposure to early postnatal stress increases corticosterone concentration which leads to increased DNA methylation. This effect results in decreased BDNF and GDNF gene expression in the striatum leading to decreased protection against subsequent insults later in life.

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Early-life short-term environmental enrichment counteracts the effects of stress on anxiety-like behavior, brain-derived neurotrophic factor and nuclear translocation of glucocorticoid receptors in the basolateral amygdala

Scientific Reports ◽

10.1038/s41598-020-70875-5 ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Akshaya Hegde ◽

Shruti Suresh ◽

Rupshi Mitra

Keyword(s):

Neurotrophic Factor ◽

Life Stress ◽

Early Life ◽

Environmental Enrichment ◽

Glucocorticoid Receptors ◽

Basolateral Amygdala ◽

Maternal Separation ◽

Nuclear Translocation ◽

Brain Derived Neurotrophic Factor ◽

Spine Density

Abstract Early life is a decisive stage for the development of physiological and psychological characteristics of an individual. Any stress or disruption of healthy development at this stage has serious long-lasting consequences for the remaining life. Unfortunately, early life stress is a common occurrence in humans and other animals. In this context, we investigated if the provision of environmental enrichment during the pre-weaning phase of rat pups and dams could alter the consequences of early-life maternal-separation stress. Pre-weaning enrichment rescued the effects of maternal separation on the excess secretion of adrenal stress hormones and anxiety-like behavior during adulthood. Enrichment also reduced the effect of stress on the spine density of basolateral amygdala neurons, a brain region critical for stress-induced facilitation of emotional behaviors. Pre-weaning enrichment, provided during early-life, blunted the effects of maternal separation stress on decreased intra-nuclear translocation of glucocorticoid receptors within the amygdala neurons when tested later in adulthood. Early-life, pre-weaning environmental enrichment also increased the amount of brain-derived neurotrophic factor within adult basolateral amygdala. Our observations showed that environmental manipulation during early formative years could be utilized to build lifelong resilience to stress. Complex naturalistic housing and sensory enrichment is, thus, an useful buffer against an impoverished and stressful childhood.

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