Vitamin D and Depression: Cellular and Regulatory Mechanisms

Abstract

Depression is caused by a change in neural activity resulting from an increase in glutamate that drives excitatory neurons and may be responsible for the decline in the activity and number of the GABAergic inhibitory neurons. This imbalance between the excitatory and inhibitory neurons may contribute to the onset of depression. At the cellular level there is an increase in the concentration of intracellular Ca within the inhibitory neurons that is driven by an increase in entry through the NMDA receptors (NMDARs) and through activation of the phosphoinositide signaling pathway that generates inositol trisphosphate (InsP) that releases Ca from the internal stores. The importance of these two pathways in driving the elevation of Ca is supported by the fact that depression can be alleviated by ketamine that inhibits the NMDARs and scopolamine that inhibits the M1 receptors that drive InsP/Ca pathway. This increase in Ca not only contributes to depression but it may also explain why individuals with depression have a strong likelihood of developing Alzheimer's disease. The enhanced levels of Ca may stimulate the formation of A to initiate the onset and progression of Alzheimer's disease. Just how vitamin D acts to reduce depression is unclear. The phenotypic stability hypothesis argues that vitamin D acts by reducing the increased neuronal levels of Ca that are driving depression. This action of vitamin D depends on its function to maintain the expression of the Ca pumps and buffers that reduce Ca levels, which may explain how it acts to reduce the onset of depression.

Vitamin D3 attenuates anxiety-like behavior in long-term ovariectomized rats with unpredictable mild stress

“…In line with these observations, lower mood symptoms occurred more frequently in women with VD 3 deficiency/insufficiency, and VD 3 improved the mood state in such women (Kjaergaard et al, 2011;Accortt et al, 2016). The possible mechanism of VD 3 action might be explained by the stimulation of VDR identified in the different brain structures involved in mood control (Berridge, 2017). VD 3 may affect dopaminergic and/ or serotoninergic neurotransmitter systems, neurotrophic factors, and/or alter the HPA axis response at the depressive state (Mizwicki and Norman, 2009;Harms et al, 2011).…”

Vitamin D protects dopaminergic neurons against neuroinflammation and oxidative stress in hemiparkinsonian rats

“…Evidences also suggest that oxidative stress plays a major role in neurodegenerative diseases, including PD [39, 54, 55]. Not only DA metabolism could contribute to that, but also mitochondrial dysfunction, leading to an increase in ROS and activated microglia, and producing NO and ROS during neuroinflammatory responses.…”

The effect of vitamin D supplement on negative emotions: A systematic review and meta‐analysis

“…The association between vitamin and mental health has been explored extensively (Landel & Wion, 2017; Lim et al, 2016). In previous decades, the effects of vitamin B were the major target of investigation (Mikkelsen, Stojanovska, & Apostolopoulos, 2016; Sachdev et al, 2005; Tiemeier et al, 2002), but vitamin D has also attracted much attention in recent years (Berk et al, 2007; Berridge, 2017; Landel & Wion, 2017; McGrath, 2017; Pittampalli, Mekala, Upadhyayula, & Lippmann, 2018). Vitamin D is a secosteroid hormone and is involved in the absorption of calcium and phosphorus in the intestine as well as being important for osteogenesis (Holick, 2004).…”