Maternal vitamin D supplementation and treadmill exercise attenuated vitamin D deficiency-induced anxiety-and depressive-like behaviors in adult male offspring rats

ABSTRACT

Background

Vitamin D is a vital neuroactive steroid for brain development and function. Vitamin D deficiency is a worldwide health problem, particularly in children and women. Gestational or developmental vitamin D deficiency is associated with an increased risk of neurodevelopmental and neuropsychiatric disorders. This study examined the effect of maternal vitamin D dietary manipulations and treadmill exercise on anxiety-and depressive-related behaviors, pro-inflammatory cytokines, and prefrontal cortex (PFC) protein levels of brain-derived neurotrophic factor (BDNF) and vitamin D receptor (VDR) in adult male offspring born to vitamin D-deficient diet (VDD)-fed dams.

Methods and Results

Female rats were provided standard diet (SD) or VDD for six weeks and then were treated with SD (started a week before mating throughout gestation and lactation) and treadmill exercise (a week before mating until gestational day 20). Male offspring were separated on postnatal day (PND) 21 and fed SD chow until PND90. Our results demonstrated that maternal vitamin D deficiency increased anxiety and depression-related behaviors, increased levels of TNF-α and IL-1β in serum, and decreased prefrontal protein expressions of BDNF and VDR in adult male offspring. However, maternal vitamin D supplementation and treadmill exercise reversed these changes alone or in combination.

Conclusion

It seems that developmental vitamin D deficiency disrupts brain development and has a long-lasting effect on VDR and BDNF signaling in the rat brain resulting in neuropsychiatric disorders in offspring. Therefore, vitamin D supplementation and physical exercise are reasonable strategies to prevent these neurobehavioral impairments.

KEYWORDS:

• Vitamin D deficiency
• VDR
• BDNF
• Depression
• Anxiety
• Offspring
• inflammation
• Vitamin D supplementation

Acknowledgment

This study was financially supported by a grant (Grant number: 64567) from Drug Applied Research Center, Tabriz University of Medical Sciences (Tabriz, Iran).

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Drug Applied Research Center, Tabriz University of Medical Sciences: [Grant Number 64567].

Notes on contributors

Faezeh Kazemi

Faezeh Kazemi, MSc of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran.

Shirin Babri

Shirin Babri, Professor of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran.

Parisa Keyhanmehr

Parisa Keyhanmehr, PhD candidate of Physiology, Semnan University of Medical Sciences, Tabriz, Iran.

Mahsa Farid-Habibi

Mahsa Farid-Habibi, PhD candidate of Neurosciences, Shahid Beheshti University of Medical Sciences, Tabriz, Iran.

Sepehr Nayebi Rad

Sepehr Nayebi Rad, Medical Student, Tehran University of Medical Sciences, Tabriz, Iran.

Fereshteh Farajdokht

Fereshteh Farajdokht, Assistant Professor of Physiology, Tabriz University of Medical Sciences, Tabriz, Iran.