The Role of Serotonin (5-HT) in Behavioral Control: Findings from Animal Research and Clinical Implications

The neurotransmitters serotonin and dopamine both have a critical role in the underlying neurobiology of different behaviors. With focus on the interplay between dopamine and serotonin, it has been proposed that dopamine biases behavior towards habitual responding, and with serotonin offsetting this phenomenon and directing the balance toward more flexible, goal-directed responding. The present focus paper stands in close relationship to the publication by Worbe et al. (2015), which deals with the effects of acute tryptophan depletion, a neurodietary physiological method to decrease central nervous serotonin synthesis in humans for a short period of time, on the balance between hypothetical goal-directed and habitual systems. In that research, acute tryptophan depletion challenge administration and a following short-term reduction in central nervous serotonin synthesis were associated with a shift of behavioral performance towards habitual responding, providing further evidence that central nervous serotonin function modulates the balance between goal-directed and stimulus-response habitual systems of behavioral control. In the present focus paper, we discuss the findings by Worbe and colleagues in light of animal experiments as well as clinical implications and discuss potential future avenues for related research.     

Bisphenol S and F: A Systematic Review and Comparison of the Hormonal Activity of Bisphenol A Substitutes

Background

Increasing concern over bisphenol A (BPA) as an endocrine-disrupting chemical and its possible effects on human health have prompted the removal of BPA from consumer products, often labeled “BPA-free.” Some of the chemical replacements, however, are also bisphenols and may have similar physiological effects in organisms. Bisphenol S (BPS) and bisphenol F (BPF) are two such BPA substitutes.

Objectives

This review was carried out to evaluate the physiological effects and endocrine activities of the BPA substitutes BPS and BPF. Further, we compared the hormonal potency of BPS and BPF to that of BPA.

Methods

We conducted a systematic review based on the Office of Health Assessment and Translation (OHAT) protocol.

Results

We identified the body of literature to date, consisting of 32 studies (25 in vitro only, and 7 in vivo). The majority of these studies examined the hormonal activities of BPS and BPF and found their potency to be in the same order of magnitude and of similar action as BPA (estrogenic, antiestrogenic, androgenic, and antiandrogenic) in vitro and in vivo. BPS also has potencies similar to that of estradiol in membrane-mediated pathways, which are important for cellular actions such as proliferation, differentiation, and death. BPS and BPF also showed other effects in vitro and in vivo, such as altered organ weights, reproductive end points, and enzyme expression.

Conclusions

Based on the current literature, BPS and BPF are as hormonally active as BPA, and they have endocrine-disrupting effects.

Citation

Rochester JR, Bolden AL. 2015. Bisphenol S and F: a systematic review and comparison of the hormonal activity of bisphenol A substitutes. Environ Health Perspect 123:643–650; http://dx.doi.org/10.1289/ehp.1408989     

Strychnine poisoning. Recovery from profound lactic acidosis, hyperthermia, and rhabdomyolysis

Strychnine poisoning results in a predictable and treatable sequence of events involving blockade of the inhibitory neurotransmitter, extensor muscle spasms, seizures, and respiratory paralysis. These spasms may lead to hyperthermia, profound lactic acidosis, and rhabdomyolysis. Acidosis is primarily attributable to lactate, as indicated by the correlation between arterial pH and log of lactic acid concentration (r = -0.878). Interruption of the strychnine blockade is the primary therapy for strychnine poisoning. Phenobarbital in moderate doses should be the first intervention and anesthetic doses should be used if necessary. Suppression of convulsions will permit successful management of the complications of strychnine poisoning. Our patient survived, even though at one point he had a pH of 6.55, a lactate level of 32 mM/liter, a temperature of 43 degrees C, and rhabdomyolysis with an increased creatine phosphokinase level of 359,000 mU/ml (5,983 mumol/s/liter).     

Towards measurement of the Healthy Ageing Phenotype in lifestyle-based intervention studies

Introduction

Given the biological complexity of the ageing process, there is no single, simple and reliable measure of how healthily someone is ageing. Intervention studies need a panel of measures which capture key features of healthy ageing. To help guide our research in this area, we have adopted the concept of the “Healthy Ageing Phenotype” (HAP) and this study aimed to (i) identify the most important features of the HAP and (ii) identify/develop tools for measurement of those features.

Methods

After a comprehensive assessment of the literature we selected the following domains: physiological and metabolic health, physical capability, cognitive function, social wellbeing, and psychological wellbeing which we hoped would provide a reasonably holistic characterisation of the HAP. We reviewed the literature and identified systematic reviews and/or meta-analysis of cohort studies, and clinical guidelines on outcome measures of these domains relevant to the HAP. Selection criteria for these measures included: frequent use in longitudinal studies of ageing; expected to change with age; evidence for strong association with/prediction of ageing-related phenotypes such as morbidity, mortality and lifespan; whenever possible, focus on studies measuring these outcomes in populations rather than on individuals selected on the basis of a particular disease; (bio)markers that respond to (lifestyle-based) intervention. Proposed markers were exposed to critique in a Workshop held in Newcastle, UK in October 2012.

Results

We have selected a tentative panel of (bio)markers of physiological and metabolic health, physical capability, cognitive function, social wellbeing, and psychological wellbeing which we propose may be useful in characterising the HAP and which may have utility as outcome measures in intervention studies. In addition, we have identified a number of tools which could be applied in community-based intervention studies designed to enhance healthy ageing.

Conclusions

We have proposed, tentatively, a panel of outcome measures which could be deployed in community-based, lifestyle intervention studies. The evidence base for selection of measurement domains is less well developed in some areas e.g. social wellbeing (where the definition of the concept itself remains elusive) and this has implications for the identification of appropriate tools. Although we have developed this panel as potential outcomes for intervention studies, we recognise that broader agreement on the concept of the HAP and on tools for its measurement could have wider utility and e.g. could facilitate comparisons of healthy ageing across diverse study designs and populations.     

Activated natural killer cells and interleukin-2 promote granulocytic and megakaryocytic reconstitution after syngeneic bone marrow transplantation in mice

Purified populations of natural killer (NK) cells were obtained from mice with severe combined immune deficiency (SCID). SCID spleen cells were cultured and activated with recombinant human interleukin-2 (rhIL- 2) in vitro. The activated NK cells were then transferred with syngeneic BALB/c bone marrow cells (BMC) and rhIL-2 into lethally irradiated syngeneic recipients to determine their effect on long-term hematopoietic reconstitution. On analysis, the transfer of rhIL-2- activated NK cells along with BMC resulted in significant increases in splenic and BM hematopoietic progenitor cells when compared with those for mice not receiving NK cells. Histologic and flow cytometric analysis showed a marked increase in granulocytic and megakaryocytic lineage cells present in the spleens of the mice receiving activated NK cells. Analysis of the peripheral blood indicated that the transfer of activated NK cells with BMC also significantly improved platelet and total white blood cell counts, with increases in segmented neutrophils. Erythroid recovery was not affected. Finally, lethally irradiated mice receiving activated NK cells and rhIL-2 along with limiting numbers of syngeneic BMC showed a marked increase in survival rate. These results show that the use of populations enriched for activated NK cells after syngeneic BM transplantation (BMT) has a profound enhancing effect on engraftment primarily affecting megakaryocytic and granulocytic cell reconstitution. Therefore, the transfer of activated NK cells and rhIL- 2 may be of clinical use to promote hematopoietic reconstitution after BMT.     

IgMs produced by two acquired immune deficiency syndrome lymphoma cell lines: Ig binding specificity and VH-gene putative somatic mutation analysis [published erratum appears in Blood 1994 Aug 1;84(3):995]

Two B-cell lines, 2F7 and 10C9, were established by single cell cloning from biopsies obtained from two acquired immune deficiency syndrome patients with Burkitt's lymphoma. Representation of the original tumors was verified by demonstration of (1) identical biallelic rearrangement of Ig genes for 2F7 and (2) shared idiotype for 10C9. Both cell lines displayed cell-surface Ig and secreted Ig (IgM lambda for 2F7, IgM kappa for 10C9). IgMs from both cell lines immunoprecipitated actin; in addition, 2F7 IgM lambda immunoprecipitated recombinant human immunodeficiency virus type 1 (HIV-1) gp 160. 2F7 IgM lambda did not react with other autoantigens (double-stranded and single-stranded DNA, actin, bovine serum albumin, IgG), whereas 10C9 IgM kappa reacted with human IgG. The 2F7 IgM heavy-chain variable region (VH) showed a 95% nucleotide homology with a previously sequenced VHIII germline gene, hv3019b9, whereas the 10C9 IgM VH showed a 95% homology with a previously sequenced VHIV germline gene, VH4.21. Use of minimally modified VH genes and demonstration of reactivity with chronically present antigens (ie, actin, HIV-1 gp 160, or human IgG) suggests that B cells in HIV-1-infected individuals proliferating in response to chronic antigenic stimulation may be at increased risk for lymphomagenesis.     

Comparing human and mouse salivary glands: A practice guide for salivary researchers

Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes.