Serotonin and calcium homeostasis during the transition period.

The transition from pregnancy to lactation puts significant, sudden demands on maternal energy and calcium reserves. Although most mammals are able to effectively manage these metabolic adaptations, the lactating dairy cow is acutely susceptible to transition-related disorders because of the high amounts of milk being produced. Hypocalcemia is a common metabolic disorder that occurs at the onset of lactation. Hypocalcemia is also known to result in poor animal welfare conditions. In addition, cows that develop hypocalcemia are more susceptible to a host of other negative health outcomes. Different feeding tactics, including manipulating the dietary cation-anion difference and administering low-calcium diets, are commonly used preventative strategies. Despite these interventions, the incidence of hypocalcemia in the subclinical form is still as high as 25% to 30% in the United States dairy cow population, with a 5% to 10% incidence of clinical hypocalcemia. In addition, although there are various effective treatments in place, they are administered only after the cow has become noticeably ill, at which point there is already significant metabolic damage. This emphasizes the need for developing alternative prevention strategies, with the monoamine serotonin implicated as a potential therapeutic target. Our research in rodents has shown that serotonin is critical for the induction of mammary parathyroid hormone-related protein, which is necessary for the mobilization of bone tissue and subsequent restoration of maternal calcium stores during lactation. We have shown that circulating serotonin concentrations are positively correlated with serum total calcium on the first day of lactation in dairy cattle. Administration of serotonin's immediate precursor through feeding, injection, or infusion to various mammalian species has been shown to increase circulating serotonin concentrations, with positive effects on other components of maternal metabolism. Most recently, preliminary data suggest that manipulation of the serotonergic axis precalving may positively affect postcalving calcium dynamics. Combined, our research suggests a potential mechanism by which serotonin acts on the mammary gland to maintain circulating maternal calcium concentrations. Further research into serotonin's potential as a therapeutic target could contribute significantly as a preventive strategy against hypocalcemia in early lactation dairy cows.

Patterns of circulating serotonin and related metabolites in multiparous dairy cows in the peripartum period.

Dairy cows are challenged to maintain Ca and glucose homeostasis during the transition period. Serotonin (5-HT) is a monoamine that modulates Ca and glucose homeostasis in rodents. Serotonin is positively correlated with Ca and glucose status in dairy cows on d 1 of lactation. However, the pattern of circulating concentrations of 5-HT over the course of a 305-d lactation is unknown. In this observational, longitudinal study, we examined the metabolite patterns of 5-HT, Ca, glucose, parathyroid hormone-related protein, and ß-hydroxybutyrate on 2 commercial dairy farms in south-central Wisconsin. Cows sampled on farm 1 were multiparous Jersey cows (n=30) that calved within a 23-d period; cows on farm 2 were multiparous Holstein cows (n=35) that calved within a 20-d period. Blood samples were collected daily between d -5 and d 10 relative to parturition and on d 30, 60, 90, 150, and 300 of lactation. Farms 1 and 2 were analyzed individually because of the presence of a farm effect in the initial analysis; a time effect was present on both farms. Concentrations of 5-HT decreased near parturition compared with prepartum by 57.9 and 29.5% on farm 1 and 2, respectively. Transition period 5-HT nadirs were observed on d 1 on farm 1, and on d 1 and 9 on farm 2. Serotonin recovered to prepartum concentrations by d 5 on farm 1. On farm 2, 5-HT recovered to prepartum concentrations by d 4, with a subsequent decrease of 34.6% on d 9 to a level similar to that observed on d 1. Furthermore, 5-HT increased markedly in cows on both farms near peak lactation (d 60, 90, and 150) and decreased on d 300. Compared with prepartum concentrations, Ca decreased by 34.2 and 11.2% on farms 1 and 2, respectively. Circulating total Ca nadir was observed on d 1 on both farms. Circulating 5-HT and circulating Ca were positively correlated during the early lactation period (d 1 to 5 and d 6 to 10) on farm 1 (r=0.31 and r=0.22, respectively) and d 6 to 10 on farm 2 (r=0.16). Circulating 5-HT and glucose were negatively correlated during the early lactation period (d 1 to 5) on farm 1 (r=-0.21) and during mid-lactation (d 30 to 150) on farm 2 (r=-0.26). Milk 5-HT and milk total Ca were positively correlated on farm 2 (r=0.34). These results demonstrate that 5-HT concentrations change dynamically throughout the transition period, with a pattern similar to that of total Ca concentrations. Further research using controlled experiments should be aimed at discerning the association between 5-HT and Ca and between 5-HT and glucose in dairy cows.

Short communication: Circulating serotonin (5-HT) concentrations on day 1 of lactation as a potential predictor of transition-related disorders.

The monoamine serotonin (5-hydroxytryptamine; 5-HT) has been described as a homeostatic regulator of lactation. Recently, our laboratory determined that 5-HT is involved in the regulation of calcium and glucose homeostasis during the transition period in rodents. More specifically, we demonstrate that 5-HT is responsible for calcium mobilization from bone and upregulation of hepatic gluconeogenic enzymes and mammary gland glucose transporters. Our objective was to investigate the correlation between circulating 5-HT concentrations and circulating ionized calcium, parathyroid hormone-related protein (PTHrP), and glucose concentrations on d 1 postpartum. We also investigated the correlation between circulating 5-HT and milk fever and ketosis incidence and severity in multiparous Holstein cows at the onset of lactation. Blood samples were collected from 42 multiparous cows on d 1 of lactation and analyzed for 5-HT, calcium, glucose, and PTHrP. Milk fever (determined subjectively for each cow on d 1 postpartum) and ketosis incidence and severity (scale 1 to 4, determined objectively for each cow during the first 10 d postpartum) were recorded for all animals. Serum 5-HT was positively correlated with serum calcium and with plasma PTHrP (r>0.37). Serum 5-HT was negatively correlated with milk fever incidence and with ketosis severity (most severe ketosis incidence recorded during the first 10 d postpartum; r<-0.33). Serum calcium and plasma glucose concentrations were negatively correlated with milk fever and ketosis severity, respectively (r<-0.39). These data indicate that 5-HT potentially plays a role in the regulation of calcium and glucose homeostasis during the transition period in cattle, which we previously demonstrated in rodents. Increased circulating concentrations of 5-HT might decrease milk fever at the onset of lactation and ketosis severity during the first 10 d postpartum in dairy cows. Understanding this physiological axis could help describe the underlying mechanisms associated with these periparturient metabolic disorders in dairy cows.