Decreased brain docosahexaenoic acid content produces neurobiological effects associated with depression: Interactions with reproductive status in female rats

Abstract

Decreased tissue levels of docosahexaenoic acid (DHA; 22:6n-3) are implicated in the etiologies of non-puerperal and postpartum depression. With the aim of determining neurobiological sequelae of decreased brain DHA content, this study examined the effects of a loss of brain DHA content and concurrent reproductive status in adult female Long-Evans rats. An alpha-linolenic acid-deficient diet and breeding protocols were used to produce virgin and parous female rats with cortical phospholipid DHA levels 23-26% lower than virgin and parous rats fed a control diet containing adequate alpha-linolenic acid. Parous dams were tested/euthanized at weaning (postnatal day 20) of the second litter; virgin females, during diestrus. Decreased brain DHA was associated with decreased hippocampal BDNF gene expression and increased relative corticosterone response to an intense stressor, regardless of reproductive status. In virgin females with decreased brain DHA, serotonin content and turnover in frontal cortex were decreased compared to virgin females with normal brain DHA. In parous dams with decreased brain DHA, the density of 5-HT(1A) receptors in the hippocampus was increased, corticosterone response to an intense stressor was increased, and the latency to immobility in the forced swim test was decreased compared to parous dams with normal DHA. These findings demonstrate neurobiological alterations attributable to decreased brain DHA or an interaction of parous status and brain DHA level. Furthermore, the data are consistent with findings in depressed humans, and thus support a role for DHA as a factor in the etiologies of depressive illnesses, particularly postpartum depression.

Figure 1. Effects of diet in reproducing females on number of pups per litter (A), average pup weight on postnatal day 1 (B), and male pup weight at weaning on postnatal day 20 (C)

Data are presented as the mean ± SEM (n = 15 per group). Male weanling pups were each from a different litter. No significant effects of diet or litter number were detected by ANOVA.

Figure 2. Effects of brain DHA status and reproductive status on BDNF mRNA and peptide levels in hippocampus

Data are presented as the mean ± SEM (n = 10–11 per group for mRNA, 8–10 for peptide). *Different from Virgin – Normal DHA (P<0.05).

Figure 3. Effects of brain DHA status and reproductive status on behavioral response in the forced swim test

Data are presented as the mean ± SEM (n = 12–14 per group). *Different from Virgin – Normal DHA (P < 0.05). ^†Different from Virgin – Decreased DHA (P < 0.05). ^‡Different from Parous – Normal DHA (P < 0.05).

Figure 4. Effects of brain DHA status and reproductive status on corticosterone secretion after minimal or intense stressors

Minimal stress was defined normal handling. The five-min test session of the forced swim test was used at the intense stressor. Data are presented as the mean ± SEM (n = 10–13 per group). *Different from Virgin – Normal DHA (P < 0.05). ^†Different from Virgin – Decreased DHA (P < 0.05). ^‡Different from Parous – Normal DHA (P < 0.05).