The Relationship between Gastrointestinal Health, Micronutrient Concentrations, and Autoimmunity: A Focus on the Thyroid.

Currently, there is a lack of understanding of why many patients with thyroid dysfunction remain symptomatic despite being biochemically euthyroid. Gastrointestinal (GI) health is imperative for absorption of thyroid-specific nutrients as well as thyroid function directly. This comprehensive narrative review describes the impact of what the authors have conceptualized as the "nutrient-GI-thyroid axis". Compelling evidence reveals how gastrointestinal health could be seen as the epicenter of thyroid-related care given that: (1) GI conditions can lower thyroid-specific nutrients; (2) GI care can improve status of thyroid-specific nutrients; (3) GI conditions are at least 45 times more common than hypothyroidism; (4) GI care can resolve symptoms thought to be from thyroid dysfunction; and (5) GI health can affect thyroid autoimmunity. A new appreciation for GI health could be the missing link to better nutrient status, thyroid status, and clinical care for those with thyroid dysfunction.

Symptoms Originally Attributed to Thyroid Dysfunction Were Instead Caused by Suboptimal Gastrointestinal Health: A Case Series and Literature Review.

The integrative and functional medicine field has drifted towards a thyroid-centric approach of care (fine-tune thyroid medication, support thyroid hormone conversion, and improve thyroid levels). However, many patients still do not improve symptomatically. Here, we show how a gut-focused clinical care model can improve thyroid function, reduce thyroid medication dose, and improve symptoms originally thought to be from thyroid dysfunction. We present a literature review on the gutthyroid axis and then document clinical application of this evidence through six case reports of how patients improved thyroid function and thyroid-related symptoms by improving their gastrointestinal health. Clinicians will likely experience better patient outcomes by integrating the contents of this paper into their practice.

Is SIBO A Real Condition?

CONTEXT: Small intestinal bacterial overgrowth (SIBO) has gained popularity on the internet in addition to certain clinical and research circles. This interest has expanded awareness of important new dietary, nutraceutical, and pharmaceutical treatments in addition to laboratory evaluation assessment options. Concomitantly, there appears a loss of parsimony regarding how to use these tools resulting in an untenable degree of testing and treatment for this condition. OBJECTIVES: A balanced review of the data regarding SIBO testing, treatment, and management with the goal of establishing non-biased best practices. DESIGN: Non-systematic review. RESULTS: The results for the review fall into two categories. Ineffective Action: Treat only SIBO labs; Treat for SIBO if no symptoms are exhibited; Recommending eating or avoiding foods because they might be good or bad for SIBO; Recommending treatments that are non-validated. Effective Action: Use SIBO breath results, in addition to history and current symptoms, to determine the best treatment; Find foods that work for patients based on dietary elimination and reintroduction; Apply validated treatment for SIBO and IBS in a logical 'step-up' like treatment approach. CONCLUSIONS: Testing and treating for SIBO can offer patients clinically significant relief. However, these tests and treatments must be applied with circumspection to prevent over-testing, over-treatment, squandering resources, or creating a fear around certain foods.

Social environment affects central distribution of estrogen receptor-α in Peromyscus californicus.

Social environment has well-established effects on an animal's social behavior and associated neuroendocrine responses. The presence of estrogen receptor alpha (ERα) in limbic system brain regions is related to the expression of a variety of social, reproductive and aggressive behaviors. We hypothesized that alterations to the social environment, specifically social isolation, would cause changes in ERα throughout the limbic system. The number of ERα immunoreactive (ERα-ir) cells within specific limbic system brain regions was quantified in male and female California mice (Peromyscus californicus), isolated or same sex pair-housed for 4 or 24 days. Peromyscus californicus is a highly social rodent species (monogamous and bi-parental) and therefore, may be particularly sensitive to manipulations of its social environment. Isolated males had a significantly greater number of ERα-ir cells in the ventromedial nucleus of the hypothalamus (VMH) and similar patterns within the bed nucleus of the stria terminalis (BST) and medial preoptic area (MPOA). Males housed for 24 days had a significantly greater number of ERα-ir cells in the BST, VMH, MPOA when compared with males housed for 4 days. Females housed for 24 days had significantly greater ERα-ir in the dentate gyrus of the hippocampus (DG) when compared with females housed for 4 days. No differences were found in the medial amygdala (MeA). These data demonstrate that social environment has region and sex specific effects on ERα-ir cells in this species. These results add to the comparative evidence regarding ERα, demonstrating a consistent role for ERα in species specific responsiveness to changes in the social environment.

Social isolation increases cell proliferation in male and cell survival in female California mice (Peromyscus californicus).

Social environment has direct effects on an animal's behavior, physiology and neurobiology. In particular, adult neurogenesis is notably affected by a variety of social manipulations, including social isolation. We hypothesized that social isolation should have particularly acute effects on neurogenesis in a highly social (monogamous and bi-parental) species such as Peromyscus californicus, the California mouse. Adult male and female P. californicus mice were housed in isolation or in same-sex pairs for 4 or 24 days. At the end of each period, either cell proliferation or cell survival was quantified with BrdU label and neuronal markers (either TuJ1 or NeuN). After 4 days, isolated males had greater cellular proliferation in the dentate gyrus of the hippocampus (DG) than pair housed males. After 24 days, isolate females demonstrated greater cell survival in the DG than paired females. Males demonstrated a similar, but non-significant pattern. No differences in cellular proliferation or cell survival were found in the subventricular zone (SVZ), or medial amygdala (MeA). These results add to the evidence which demonstrates that neurogenic responses to environmental conditions are not identical across species. These data may be critical in understanding the functional significance of neurogenesis as it relates to the interactions between social systems, social environment and the display of social behaviors.

Neuroscience and Global Learning.

Traditional study abroad experiences take a variety of forms with most incorporating extensive cultural emersion and a focus on global learning skills. Here we ask the question: Can this type of experience co-exist with a quality scientific experience and continued progression through a typically rigorous undergraduate neuroscience curriculum? What are the potential costs and benefits of this approach? How do we increase student awareness of study abroad opportunities and inspire them to participate? We outline programs that have done this with some success and point out ways to cultivate this approach for future programs. These programs represent a variety of approaches in both their duration and role in a given curriculum. We discuss a one-week first year seminar program in Berlin, a summer study abroad course in Munich and Berlin, semester experiences and other options offered through the Danish Institute for Study Abroad in Copenhagen. Each of these experiences offers opportunities for interfacing global learning with neuroscience.

Neuroscience study abroad: developing a short-term summer course.

Collaborative and international scientific efforts continue to be of increasing importance in the development of successful educational and research programs. The goal of our study abroad program, Neuroscience Seminar in Germany, is to bring this fact to light for undergraduates and make them aware of the global opportunities that exist in the neurosciences and related biological sciences. Here we discuss our experience of conducting a four-week summer study abroad course in collaboration with two universities associated with the German Graduate Schools of Neuroscience: Munich Center for Neurosciences - Ludwig-Maximilians-Universität (MCN-LMU) and Charité - Universitätsmedizin, Berlin (a joint institution of the Freie Universität and the Humboldt-Universität). This course combined the historical foundations of neuroscience in Germany with current research programs at these two prominent German research universities. Two weeks were spent at each location and faculty members from the participating universities provided seminars, laboratory exercises, demonstrations and tours. Students were presented with background reading and lecture material prior to the seminars and activities. Additionally, they were responsible for leading seminar-style class discussions through brief presentations and submitting written critical analyses of primary research papers associated with the laboratory exercises. These assignments provided a means to assess learning outcomes, coupled with course evaluations. Overall, this experience may serve as a template for those interested in study abroad course development and research opportunities in the neurosciences.

Social environment alters central distribution of estrogen receptor alpha in juvenile prairie voles.

It is well established that social environment, particularly isolation, has a significant impact on social behaviors and neuroendocrine responses. Estrogen receptor alpha (ERalpha) expression in limbic structures and associated nuclei is related to the display of social behaviors. We hypothesized that the stress of isolation would cause changes in the pattern of ERalpha expression in the brain. Using a highly social (typically monogamous and biparental) rodent species, the prairie vole (Microtus ochrogaster), we housed juvenile voles with a sibling, stranger or in isolation for either 4 days or 21 days. Housing manipulations began following weaning from parents and group housed siblings. Rodents may be especially sensitive to manipulations of their social environment during this juvenile period. In particular, female prairie voles are induced ovulators, reliant upon exposure to an unrelated male (male urine) to become reproductively active. ERalpha immunoreactivity was quantified in the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BST), ventromedial nucleus of the hypothalamus (VMH) and medial amygdala (MeA). Significantly fewer ERalpha immunoreactive (ERalpha-ir) cells were labeled in the MPOA and BST of females isolated for 21 days compared with stranger housed females. Non-significant differences were shown in the VMH and MeA of females. No differences were found in voles isolated for 4 days. These results suggest that female prairie voles may be more sensitive than males to manipulations of their social environment during the juvenile period.

Oxytocin, vasopressin and sociality.

The neurobiology of social behaviour is interwoven with autonomic, endocrine and other homoeostatic processes responsible for the adaptive functions of reproduction and survival. Young mammals are dependent on their mothers for nourishment, and the interaction between the mother and infant may be a physiological and neuroendocrine prototype for mammalian sociality. Although these adaptive functions of the mother-infant social behavioural dyad are obvious, adult social interactions, including social bonds, also are important to health and survival. Two neuropeptides, oxytocin (OXT) and arginine vasopressin (AVP), have been repeatedly implicated in mammalian social behaviours and emotional states that support sociality. Although best known for their roles in reproduction and homoeostasis, these peptides play a central role in the activation and expression of social behaviours and emotional states. Recent studies from our work with the prairie vole (Microtus ochrogaster), reviewed here, reveal a role for both OXT and AVP in behavioural and endocrine changes during social interactions, and also changes that are associated with the absence of social interactions (i.e. social isolation).

Pup exposure elicits hippocampal cell proliferation in the prairie vole.

The onset of parental behavior has profound and enduring effects on behavior and neurobiology across a variety of species. In some cases, mere exposure to a foster neonate (and a subsequent parental response) can have similar effects. In the present experiment, we exposed adult male and female prairie voles (Microtus ochrogaster) to two foster pups for 20 min and quantified cell proliferation in the dentate gyrus of the hippocampus (DG), medial amygdala (MeA) and cortical amygdala (CorA). Prairie voles are highly social rodents that typically display biparental care and spontaneous parental care when exposed to foster pups. Comparisons were made between the animals that responded parentally or non-parentally towards the pups, as well as control conditions. Cell proliferation was assessed using injections of 5-bromo-2'-deoxyuridine (BrdU) and immunocytochemical localization of this marker. The phenotype of the cells was determined using double label immunofluoresence for BrdU and TuJ1 (a neuronal marker). An increase in cell proliferation in the DG was seen in animals exposed to pups. However, animals that responded non-parentally had a greater number of BrdU labeled cells in the DG compared to those that responded parentally. The majority of BrdU labeled cells co-expressed TuJ1 across all groups. These results demonstrate that exposure to a foster pup and the behavioral reaction to it (parental or non-parental) are associated with site-specific changes in cell proliferation.

Social environment regulates corticotropin releasing factor, corticosterone and vasopressin in juvenile prairie voles.

Stressful social conditions, such as isolation, that occur during sensitive developmental periods may alter present and future social behavior. Changes in the neuroendocrine mechanisms closely associated with affiliative behaviors and stress reactivity are likely to underlie these changes in behavior. In the present study, we assessed the effects of post-weaning social housing conditions on the neuropeptides arginine vasopressin (AVP) and oxytocin (OT), and components of the hypothalamic-pituitary-adrenal axis (corticotropin releasing factor: [CRF], and corticosterone: [CORT]) in the prairie vole (Microtus ochrogaster), a socially monogamous bi-parental rodent. Following weaning at 21 days of age, prairie voles were maintained in one of three housing conditions: social isolation (isolate), paired with a same sex sibling (sibling) or paired with a stranger (stranger) of the same sex and age. Housing conditions were maintained for either 4 or 21 days. Central CRF, AVP and OT immunoreactivity (ir) were quantified and circulating plasma CORT, AVP and OT were assayed. Isolated voles had higher CRF-ir in the paraventricular nucleus of the hypothalamus (PVN) compared with sibling and stranger housed voles. Plasma CORT was significantly higher in isolates. AVP-ir was significantly lower in the PVN of isolate females compared to either sibling females or stranger females. However, AVP-ir was significantly higher in the supraoptic nucleus (SON) of isolates compared to siblings. There were no differences in central OT-ir or plasma OT. These results identify neuroendocrine mechanisms which respond to isolation and potentially modulate behavior.

Assessing the consequences of the pesticide methoxychlor: neuroendocrine and behavioral measures as indicators of biological impact of an estrogenic environmental chemical.

Japanese quail provide an advantageous avian model for assessing long-term biological consequences of endocrine disrupting chemicals (EDCs). These studies examined route of exposure and vulnerability to biological impact of EDCs over the life cycle in a precocial avian model, the Japanese quail. Embryonic exposure occurs with maternal deposition and methoxychlor (MXC) accumulated with maternal exposure. Egg injections of MXC or estradiol at selected stages of development impacted hypothalamic neuroendocrine systems in hatchlings and affected sexual maturation, with evidence for long-term effects on neurotransmitters and male behavior. Two-generation dietary studies were conducted to examine transgenerational effects of EDCs. Adult quail (P1) were exposed to dietary MXC (0, 0.5 and 5 ppm), with continued exposure in their offspring (F1), and control diet for all F2 chicks. Toxicological end points, including fertility, hatching success, and 14-day viability were unaffected. F1 and F2 male offspring from MXC-treated pairs MXC had impaired mating behavior and altered plasma hormones. These studies confirm neuroendocrine and behavioral measures as reliable indices of exposure to an estrogenic EDC. Moreover, maternal deposition remains a primary route of EDC exposure, with potential deleterious consequences for field birds, especially precocial species that appear to be particularly sensitive to embryonic EDC exposure.

Immediate early gene expression associated with induction of brooding behavior in Japanese quail.

Certain species can be induced to foster infant or neonatal animals through the process of sensitization. We induced brooding behavior in adult Japanese quail through repeated exposure to foster chicks across five 20-min trials. Brooding behavior was characterized by a bird allowing chicks to approach and remain underneath its wings while assuming a distinctive stationary crouching posture, preening, and feather fluffing. Birds who did not show brooding behavior actively avoided chicks. Among the birds that brooded chicks, females brooded chicks for longer durations compared to males. Brooding females continued a regular daily egg laying pattern; males showed no significant changes in testosterone levels after exposure to chicks. In a second experiment, we measured expression of two immediate early gene (IEG) protein products, ZENK and Fos, to identify the brain regions activated or inhibited by brooding behavior in females. ZENK and Fos expression in brooding or sensitized females (SF) were compared with expression in nonmaternal females with chicks (NMF) and with females without chicks and with blocks as control objects (BL). There was a reduced density of ZENK-like immunoreactive (ZENK-lir) cells in the medial preoptic nucleus (POM) in NMF birds. In SF birds, the density of Fos-like immunoreactive (Fos-lir) cells was elevated in the bed nucleus stria terminalis, medial portion (BSTm), and ectostriatum (E). These experiments begin to define the neural circuitry underlying brooding behavior in Japanese quail, and establish a model for future studies of the neural mechanisms of avian parental behavior.