Effect of high-fat diet-induced obesity on maternal mouse behaviour prepartum and postpartum

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Moazzam, Showall
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Background: Obesity is prevalent in women of childbearing age. Approximately 18.5 to 38.5% of women in North America are considered to be obese at the time they become pregnant. Obesity in pregnancy increases the risk of developing maternal mental behavioural disorders, which include anxiety and depression. These disorders may be influenced by changes in lactogen levels and signalling during pregnancy and at time of delivery. Brain-derived neurotrophic factor (BDNF) is one possible biomarker of mental health problems. Low serum BDNF levels during pregnancy are associated with depression during the peripartum period. Here, a high-fat diet (HFD)-induced mouse model of obesity was used to study the relationship between HFD and maternal behaviour outcome. It was hypothesized that HFD-induced obesity in pregnancy increases risk of impaired maternal behaviour, an anxiety-like phenotype, compromised working memory and anhedonia that is associated with a reduction in total brain BDNF levels in CD-1 mice prepartum and postpartum. It was further hypothesized that increasing placental lactogen availability will reduce risk of impaired maternal behaviour. Approach: Four-week old wild-type CD-1[WT] and CD-1[171hGH/CS] mice, which contain a transgene that includes genes coding for human placental lactogen, were fed a HFD (fat=60 kcal%; carbohydrate=20 kcal%; protein=20 kcal%) or regular chow diet (RCD; fat=14 kcal%; carbohydrate=60 kcal%; protein=26 kcal%) throughout the study. Mice were bred after five weeks on the diet. Maternal behaviour was assessed in all mice by testing nest building prepartum, followed by nursing and pup-retrieval behaviour postpartum. Anxiety-like behaviour was assessed prepartum and postpartum via an elevated-plus maze (EPM) test. Working memory was assessed using a novel object recognition (NOR) test postpartum. Anhedonia was assessed pre-weaning and post-weaning in the postpartum period using a sucrose preference test. BDNF RNA levels were measured by quantitative real-time reverse transcriptase-polymerase chain reaction and total brain protein levels via BDNF-specific enzyme linked immunosorbent assay and, through collaboration, by protein immunoblotting. Results: HFD-induced obesity impaired nest building and pup-retrieval behaviour in CD-1[WT] mice but had no significant negative effect on these behaviours in CD-1[171hGH/CS] mice. HFD- induced obesity impaired postpartum anxiety-like behaviour, working memory, and was associated with anhedonia in dams pre-weaning in the CD-1[WT] mice. Conversely, HFD-induced obesity did not impair anxiety-like behaviour and working memory in CD-1[171hGH/CS] mice. An increase in brain BDNF levels in non-pregnant and pregnant CD-1[WT] mice on HFD was observed in the postpartum period. However, in the CD-1[171hGH/CS] mice, higher BDNF levels were seen prepartum in non-pregnant and pregnant mice on a RCD, but only in the pregnant mice postpartum. Conclusions: A negative effect of HFD-induced obesity on maternal behaviour, postpartum anxiety, working memory and anhedonia was observed in CD-1[WT] but not CD-1[171hGH/CS] mice. Furthermore, the negative effects observed on maternal behaviour in CD-1[WT] mice, and specifically pup retrieval, is associated with increased total brain BDNF levels in the postpartum period. This increase was not seen in the CD-1[171hGH/CS] mice where pup-retrieval was unaffected by HFD. This raises the possibility that the lack of response in the CD-1[171hGH/CS] mice to the negative effects induced by HFD in the in the CD-1[WT] mice might be mitigated by a direct or indirect effect of the products of the transgene, including on brain BDNF levels.
Pregnancy, High-fat diet, Behaviour, Anxiety, Working memory, Anhedonia, BDNF, Maternal behaviour
Moazzam, Showall, et al. "Effects of high fat diet-induced obesity and pregnancy on prepartum and postpartum maternal mouse behavior." Psychoneuroendocrinology 126 (2021): 105147.