Vitamin D is crucial for maternal care and offspring social behaviour in rats

Abstract

Early life vitamin D plays a prominent role in neurodevelopment and subsequent brain function, including schizophrenic-like outcomes and increasing evidence for an association with autism spectrum disorder (ASD). Here, we investigate how early life vitamin D deficiency during rat pregnancy and lactation alters maternal care and influences neurodevelopment and affective, cognitive and social behaviours in male adult offspring. Sprague-Dawley rats were placed on either a vitamin D control (2195 IU/kg) or deficient diet (0 IU/kg) for five weeks before timed mating, and diet exposure was maintained until weaning of offspring on postnatal day (PND) 23. MRI scans were conducted to assess brain morphology, and plasma corticosterone levels and neural expression of genes associated with language, dopamine and glucocorticoid exposure were characterised at PND1, PND12 and 4 months of age. Compared to controls, vitamin D-deficient dams exhibited decreased licking and grooming of their pups but no differences in pup retrieval. Offspring neurodevelopmental markers were unaltered, but vitamin D-deficient pup ultrasonic vocalisations were atypical. As adults, males that had been exposed to vitamin D deficiency in early life exhibited decreased social behaviour, impaired learning and memory outcomes and increased grooming behaviour, but unaltered affective behaviours. Accompanying these behavioural changes was an increase in lateral ventricle volume, decreased cortical FOXP2 (a protein implicated in language and communication) and altered neural expression of genes involved in dopamine and glucocorticoid-related pathways. These data highlight that early life levels of vitamin D are an important consideration for maternal behavioural adaptations as well as offspring neuropsychiatry.

Maternal vitamin D deficiency and developmental origins of health and disease (DOHaD)

“…Pre-and post-natal VDD increased learning and memory deficits and resulted in elevated depressive-like and anxiety-like behaviors in male mice (Fu et al 2017). Similar learning and memory deficits were reported in male rats subjected to VDD during the perinatal period (Yates et al 2018). Deviations in pup ultrasonic vocalizations reduced social behaviors, and an increase in stereotypical behaviors was also detected in this group, which might be attributed to reduced maternal care provided by VDD dams.…”

“…Recent findings link low vitamin D status to adverse neurological outcomes such as autism spectrum disorder (ASD), schizophrenia, depression, multiple sclerosis and dementia (Eyles et al 2011, Yates et al 2018. Accumulating evidence suggests that vitamin D is metabolized in various cells within the central nervous system, such as glial cells, neurons and astrocytes (Cui et al 2017).…”

Effects of vitamin D in the nervous system: Special focus on interaction with steroid hormone signalling and a possible role in the treatment of brain cancer

“…Dysregulation of glucocorticoid signalling in the brain is of interest in view of the role(s) of glucocorticoids in pathological conditions, including depression . In addition, glucocorticoids have important function in foetal development, a role also attributed to vitamin D. Yates et al reported effects on neurodevelopment and social behaviours as a result of vitamin D deficiency during rat pregnancy. In these studies, genes involved in glucocorticoid‐related pathways were among those affected.…”

“…As noted above, many studies indicate that vitamin D plays a role for development and function of the nervous system. Deficiency or insufficiency of this vitamin during gestation or in early life has been associated with several dysfunctions, including schizophrenic‐like conditions and autism spectrum disorder . In view of the findings indicating links between vitamin D and steroid hormone synthesis and signalling, it is interesting to note that abnormal levels of steroids are found in individuals with autism.…”

Prenatal Adversity Modulates the Quality of Maternal Care Via the Exposed Offspring

“…This is important because variations in maternal care in rodents, independent of prenatal exposures, have been linked to altered offspring behavior and persistent changes in the offspring brain . High‐fat diet (HFD), low‐protein diet (LPD), chronic psychological stress, physical restraint, chronic corticosterone administration, and vitamin D deficiency in pregnancy are just some of the stressors that have been reported to induce changes in maternal behavior in animal models. There is very little data on the consequences, specifically of HFD, in a human pregnancy on maternal care but maternal obesity is a well‐known risk factor for maternal depression and anxiety, and there are studies that link maternal obesity to lower quality maternal attachment and maternal parenting stress .…”