Behavioural Effects of Adult Vitamin D Deficiency in BALB/c Mice Are not Associated with Proliferation or Survival of Neurons in the Adult Hippocampus

Abstract

Epidemiological studies have shown that up to one third of adults have insufficient levels of vitamin D and there is an association between low vitamin D concentrations and adverse brain outcomes, such as depression. Vitamin D has been shown to be involved in processes associated with neurogenesis during development. Therefore, the aim of this study was to test the hypothesis that adult vitamin D (AVD) deficiency in BALB/c mice was associated with (a) adult hippocampal neurogenesis at baseline, b) following 6 weeks of voluntary wheel running and (c) a depressive-like phenotype on the forced swim test (FST), which may be linked to alterations in hippocampal neurogenesis. We assessed proliferation and survival of adult born hippocampal neurons by counting the number of cells positive for Ki67 and doublecortin (DCX), and incorporation of 5-Bromo-2’-Deoxyuridine (BrdU) within newly born mature neurons using immunohistochemistry. There were no significant effects of diet on number of Ki67+, DCX+ or BrdU+ cells in the dentate gyrus. All mice showed significantly increased number of Ki67+ cells and BrdU incorporation, and decreased immobility time in the FST, after voluntary wheel running. A significant correlation was found in control mice between immobility time in the FST and level of hippocampal neurogenesis, however, no such correlation was found for AVD-deficient mice. We conclude that AVD deficiency was not associated with impaired proliferation or survival of adult born neurons in BALB/c mice and that the impact on rodent behaviour may not be due to altered neurogenesis per se, but to altered function of new hippocampal neurons or processes independent of adult neurogenesis.

Vitamin D Improves Neurogenesis and Cognition in a Mouse Model of Alzheimer’s Disease

“…A first study showed an enhanced proliferation (yet not translated into enhanced production of functional neurons) in the dentate gyrus of 2-month-old transgenic mice unable to produce calcitriol [ 44 ]. A second study observed no modification in proliferation or survival of neurons in the dentate gyrus of 6-month-old wild-type mice [ 46 ]. However, due to the lack of data at a more advanced age, the comparison with our results remains limited, leaving open the option that hippocampal cell proliferation is drastically reduced in aged knockout or vitamin D-deprived mice.…”

“…Fourth, an adult hypovitaminosis D increases the proliferation of neuroblasts in the sub-granular zone of the hippocampus and alters their neuronal differentiation [ 44 ]. However, calcitriol enhances proliferation in secondary cultures of neural progenitor cells [ 45 ] and a recent study failed to report any impact on hippocampal proliferation in adult mice [ 46 ].…”

Chronic vitamin D insufficiency impairs physical performance in C57BL/6J mice

“…Recently a study silencing VDR expression with siRNA in muscle stem cells (C2C12) demonstrated inhibition of myogenic differentiation [ 21 ]. Dietary elimination of vitamin D has also been reported to impair performance, including lesser grip strength in mice [ 22 ] and swim endurance [ 23 ], while 1α-OH vitamin D treatment in ovariectomized rats was associated with increases in muscle strength, but not with muscle fatigue [ 24 ].…”

Postnatal Vitamin D Intake Modulates Hippocampal Learning and Memory in Adult Mice

“…The hippocampus is crucial for brain function and homeostasis such as learning, memory, and aging. Hippocampal abnormality is associated with numerous neuropsychiatric and degenerative disorders (DeCarolis and Eisch, 2010 ), whereby a link between VD and hippocampal homeostasis was suggested (Briones and Darwish, 2012 ; Zhu et al, 2012 ; Groves et al, 2016 ). But to date few have studied the impact of postnatal VD intake abnormality on hippocampal development and function such as learning and memory.…”