Alzheimer’s disease (AD), a neurodegenerative disorder, is the leading cause of dementia in the world whose aetiology is still unclear. AD was always related to ageing though there have been instances where people at an early age also succumb to this disease. With medical advancements, the mortality rate has significantly reduced which also makes people more prone to AD. AD is rare, yet the prominent disease has been widely studied with several hypotheses trying to understand the workings of its onset. The most recent and popular hypothesis in AD is the involvement of mitochondrial dysfunction and calcium homeostasis in the development of the disease though their exact roles are not known. With the sudden advent of the mitochondrial calcium uniporter (MCU), many previously known pathological hallmarks of AD may be better understood. Several studies have shown the effect of excess calcium in mitochondria and the influence of MCU complex in mitochondrial function. In this article, we discuss the possible involvement of MCU in AD by linking the uniporter to mitochondrial dysfunction, calcium homeostasis, reactive oxygen species, neurotransmitters and the hallmarks of AD – amyloid plaque formation and tau tangle formation.

The study was undertaken to explore the amelioration of chronic fluoride (F) toxicity (with low and normal Ca) in rats. The study was conducted in two phases. In phase I (6 months), seventy-six Wistar, weanling male rats were assigned to four treatment groups: normal-Ca (0·5 %) diet (NCD), Ca+F − ; low-Ca (0·25 %) diet (LCD), Ca − F − ; NCD +100 parts per million (ppm) F water, Ca+F+; LCD +100 ppm F water, Ca − F+. In phase II (reversal experiment, 3 months), LCD was replaced with the NCD. Treatment groups Ca+F+ and Ca − F+ were divided into two subgroups to compare the effect of continuation v. discontinuation along with Ca supplementation on reversal of chronic F toxicity. In phase I, significantly reduced food efficiency ratio (FER), body weight gain (BWG), faecal F excretion, serum Ca and increased bone F deposition were observed in the treatment group Ca − F+. Reduced serum 25-hydroxy-vitamin D3, increased 1,25-dihydroxy-vitamin D3 and up-regulation of Ca-sensing receptor, vitamin D receptor and S100 Ca-binding protein G (S100G) were observed in treatment groups Ca − F −  and Ca − F+. In phase II (reversal phase), FER, BWG and serum Ca in treatment groups Ca − F+/Ca+F −  and Ca − F+/Ca+F+ were still lower, as compared with other groups. However, other variables were comparable. Down-regulation of S100G was observed in F-fed groups (Ca+F+/Ca+F+ and Ca − F+/Ca+F+) in phase II. It is concluded that low Ca aggravates F toxicity, which can be ameliorated after providing adequate Ca and F-free water. However, chronic F toxicity can interfere with Ca absorption by down-regulating S100G expression irrespective of Ca nutrition.

Most dairy cows exhibit different degrees of hypocalcaemia around calving because the gestational Ca requirements shift to the disproportionately high Ca requirements of lactation. Ca homeostasis is a robust system that effectively adapts to changes in Ca demand or supply. However, these adaptations often are not rapid enough to avoid hypocalcaemia. A delay in the reconfiguration of intestinal Ca absorption and bone resorption is probably the underlying cause of this transient hypocalcaemia. Several dietary factors that affect different aspects of Ca metabolism are known to reduce the incidence of milk fever. The present review describes the interactions between nutrition and Ca homeostasis using observations from cattle and extrapolations from other species and aims to quantitatively model the effects of the nutritional approaches that are used to induce dry cows into an early adaptation of Ca metabolism. The present model suggests that reducing dietary cation–anion difference (DCAD) increases Ca clearance from the blood by dietary induction of systemic acidosis, which results in hypercalciuria due to the loss of function of the renal Ca transient receptor potential vanilloid channel TRPV5. Alternatively, reducing the gastrointestinal availability of Ca by reducing dietary Ca or its nutritional availability will also induce the activation of Ca metabolism to compensate for basal blood Ca clearance. Our model of gastrointestinal Ca availability as well as blood Ca clearance in the transition dairy cow allowed us to conclude that the most common dietary strategies for milk fever prevention may have analogous modes of action that are based on the principle of metabolic adaptation before calving.

Impaired endoplasmic reticulum (ER) stress response has been suggested as a possible pathophysiological mechanism of bipolar disorder (BD). The expression of ER stress-related genes, spliced form or unspliced form of XBP1, GRP78 (HSPA5), GRP94 (HSP90B1), CHOP (DDIT3), and calreticulin (CALR), were examined in lymphoblastoid cells derived from 59 patients with BD and 59 age- and sex-matched control subjects. Basal mRNA levels and induction by 4 h or 12 h of treatment with two ER stressors, thapsigargin or tunicamycin, were examined using real-time quantitative reverse transcription–polymerase chain reaction. Induction of the spliced form of XBP1 as well as total XBP1 by thapsigargin was significantly attenuated in patients with BD. Induction of GRP94 by thapsigargin was also decreased in the BD group. A haplotype of GRP94, protective against BD, exhibited significantly higher GRP94 expression upon ER stress. This report confirms and extends earlier observations of impaired ER stress response in larger samples of lymphoblastoid cell lines derived from BD patients. Altered ER stress response may play a role in the pathophysiology of BD by altering neural development and plasticity.

Although the biological requirement for vitamin D can be met by epidermal exposure to UV light, there are a number of conditions where this production does not occur or is not sufficient to meet biological needs. When this happens, vitamin D must be consumed and is a nutrient. However, two distinct observations have caused researchers to rethink certain dogma in vitamin D biology. First, it appears that in addition to the hormonally active form of 1,25 dihydroxyvitamin D (1,25(OH)2D), circulating levels of 25 hydroxyvitamin D have a critical importance for optimal human health. This and other data suggest that extra-renal production of 1,25(OH)2D contributes to Ca homeostasis and cancer prevention. Second, in addition to its role in the transcriptional activation of genes through the vitamin D receptor there is now compelling evidence that 1,25(OH)2D has a second molecular mode of action; the rapid activation of second-messenger and kinase pathways. The purpose of this second mode of action is only now being explored. The present review will discuss how these two areas are reshaping our understanding of vitamin D metabolism and action.

Adequate blood calcium (Ca) concentrations are a prerequisite to maintain several physiological functions of mammals such as pig and ruminants. Thus, blood Ca levels have to be regulated within very close limits. This is basically ensured through the coordinated effects of the calcitropic hormones parathyroid hormone (PTH) and calcitriol (1,25-dihydroxyvitamin D3). If plasma Ca decreases, one main effect of subsequently secreted PTH is the stimulation of renal reabsorption of Ca from the glomerular filtrate to reduce urinary Ca loss. Another important action of PTH is the induction of the renal enzyme 1[@@@]\rmalpha [@@@]-hydroxylase, which is responsible for the production of calcitriol. In most monogastric species, so far investigated, one of the most important effects of calcitriol is to stimulate active absorption of Ca from the gastrointestinal tract, particularly the upper small intestines, via a vitamin D-receptor-mediated genomic action. Whether this concept can be transferred without any constrictions to ruminants is still under discussion. Marked interspecies differences have to be recognized with respect to ruminant or non-ruminant animals, particularly with respect to individual segments along the gastrointestinal axis and with respect to vitamin D sensitivity of Ca transport mechanisms. This review will elucidate some of the current concepts related to the mechanisms and sites of Ca absorption in pigs and ruminants with special emphasis on dairy cows where Ca homeostasis is occasionally compromised at the time of parturition.

Na-induced calciuria has been well documented and provides a physiological basis for the proposed role of dietary Na (or salt) as a risk factor for osteoporosis. However, the evidence is based primarily on acute salt-loading studies, and there are insufficient data on the effects of high salt intake on net Ca retention to predict long-term effects on bone health. Results of investigations on salt and bone turnover, as assessed by bone biomarkers, are inconsistent, but the large variations in inter-individual response to acute and chronic Na loading may be related to salt sensitivity. Results of cross-sectional and prospective investigations on high salt intake and long-term bone health are inconclusive, probably reflecting the difficulty of conducting such studies in free-living populations. However, the mean urinary Ca loss of 1 mmol/100 mmol Na suggests that chronic changes in salt intake may have large effects on Ca and bone balance, especially in individuals with a reduced capacity to compensate for Na-induced Ca loss. Investigating the relationship between salt intake and bone health requires a greater focus on whole diets (including components such as K, Mg, P and protein), reliable measures of salt intake, appropriate bone health outcome measures, and improved subject characterisation (e.g. salt sensitivity). The reasons for inter-individual variability should be explored using post-genomic techniques.