Journal of Neuroendocrinology最新文献

The neurocognitive and psychiatric effects of Cushing's syndrome (CS) are well recognized and negatively impact quality of life. The aim of this systematic review is to compare neurocognitive disease, psychiatric symptoms, and structural brain changes in patients with Cushing's disease (CD)/CS and those with non-functioning pituitary adenoma (NFPA), both before and after surgical treatment, and in comparison to healthy controls. Possible predictors of persistent neurocognitive symptoms and reduced quality of life in patients with CS are highlighted. We reviewed the English literature published in Medline/Pubmed until 2021 to identify eligible studies. This systematic review was registered on Prospero and reported following the PRISMA statement guidelines. The initial literature search yielded 1772 articles, of which 1096 articles remained after removing duplicates. After excluding case reports, animal studies, narrative reviews, comparative reviews, and articles not in English, 86 papers underwent full-text review. Studies eligible for inclusion met the following criteria: (1) described patients with CD/CS, (2) reports of psychiatric symptoms, (3) written in English or with available English translation, and (4) published in a peer-reviewed journal. The full-text review process identified 40 eligible studies. The 40 studies included a total of 2603 participants with CD or CS, with 45.2% of the total participants having CD. The majority of studies were case-control studies and used validated questionnaires such as the Beck's Depression Index, Trail Making Test, Hospital Anxiety and Depression Scale, and Cushing Quality of Life for screening. Compared to NFPA controls, patients with CD who had greater baseline serum cortisol levels had worse cognitive function, even after surgical remission. This suggests a possible association between greater baseline cortisol levels in patients with CS and persistent cognitive impairment. A longer duration of uncontrolled CS was associated with worse cognitive function; however, there was no association found between the length of remission and memory. Overall brain volume was increased in patients in remission from CD compared to active disease. However, temporal and frontal lobe volumes did not recover to normal volumes. Patients with CS experience neurocognitive dysfunction, psychiatric disorders, and diminished quality of life, and symptoms may persist after curative surgery. We found several factors consistently associated with persistent cognitive and neuropsychiatric symptoms in patients with CS including higher pre-operatively baseline cortisol production, longer duration of disease, frontal and temporal lobe atrophy, and the presence of cognitive and neuropsychiatric symptoms at baseline. Larger prospective studies are required to validate these findings.

The alterations of phenotypic traits (morphology, endocrine physiology, and behavior) in response to predictable environmental cues across life-history stages in seasonally breeding birds enable successful culmination of reproduction. The present study elucidated the plasticity of the hypothalamic-pituitary-adrenal (HPA) axis in a subtropical free-living finch, Amandava amandava amandava, and suggests the crucial role of the baseline corticosterone (CORT) to coordinate energetic readiness across life-history stages. Birds were captured monthly from an area (25.1337° N 82.5644° E) in Uttar Pradesh, India, from June 2014 to May 2015. Only male birds were included in this study corresponding to different life-history stages (6/life-history stage; 2/month): pre-breeding (June-August), breeding (September-November), post-breeding (December-February), and quiescent phases (March-May). The pituitary expression of adrenocorticotropic hormone (ACTH), adrenal interrenal cell morphometry, and plasma level of the CORT showed varied patterns across life-history stages. The density and immunointensity of the ACTH-immunoreactive corticotropes and the interrenal cell number increased along with the significant plasma CORT elevation during the breeding cycle (both pre-breeding and breeding phases). CORT might facilitate the energy demand for the display of sexual behavior (nest-building, courtship), testicular recrudescence, and foraging of food for offspring during the breeding cycle. On the contrary, plasma CORT decrease in the post-breeding and quiescent phases might enable the bird to molt avoiding the protein catabolic effect of the hormone. Given the complexity involved in the study of baseline CORT in free-living birds, more studies are needed to better understand the crucial role of the HPA axis in the modulation of life-history stages in this and other subtropical avian species.

Juvenile male hamsters exposed to chronic social stress eat more, gain weight, and have larger fat pads. The purpose of the present study was to address possible changes in food hoarding and orexin/hypocretin innervation in response to social stress. Male hamsters in early adolescence were exposed to a resident-intruder social stress paradigm or control condition daily for 2 weeks. Metabolism-related physiological measures and behaviors were tracked, and brains were immunocytochemically labeled for orexin-A. Our data confirm our previous observations on appetite, weight gain, and obesity, and showed a strong trend toward enhanced food hoarding as in prior studies. In addition, there were no statistically significant differences in orexin innervation in any brain area analyzed. However, unique correlation patterns were observed between orexin innervation and appetite or metabolic outcome. In particular, opposite correlations were observed between groups within the dorsal raphe nucleus, lateral parabrachial nucleus, and nucleus of the solitary tract. These opposite patterns of correlations suggest chronic social stress causes site-specific alterations in synaptic activity in relation with these behaviors.

Different populations of hypothalamic kisspeptin (KISS1) neurons located in the rostral periventricular area of the third ventricle (RP3V) and arcuate nucleus (ARC) are thought to generate the sex-specific patterns of gonadotropin secretion. These neuronal populations integrate gonadal sex steroid feedback with internal and external cues relayed via the actions of neurotransmitters and neuropeptides. The excitatory amino acid neurotransmitter glutamate, the main excitatory neurotransmitter in the brain, plays a role in regulating gonadotropin secretion, at least partially through engaging KISS1 signaling. The expression and function of individual glutamate receptor subtypes in KISS1 neurons, however, are not well characterized. Here, we used GCaMP-based calcium imaging and patch-clamp electrophysiology to assess the impact of activating individual ionotropic (iGluR) and group I metabotropic (mGluR) glutamate receptors on KISS1 neuron activity in the mouse RP3V and ARC. Our results indicate that activation of all iGluR subtypes and of group I mGluRs, likely mGluR1, consistently drives activity in the majority of KISS1 neurons within the RP3V and ARC of males and females. Our results also revealed, somewhat unexpectedly, sex- and region-specific differences. Indeed, activating (S)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) type iGluRs evoked larger responses in female ARC^KISS1 neurons than in their male counterparts whereas activating group I mGluRs induced larger responses in RP3V^KISS1 neurons than in ARC^KISS1 neurons in females. Together, our findings suggest that glutamatergic neurotransmission in KISS1 neurons, and its impact on the activity of these cells, might be sex- and region-dependent in mice.

Songbird vocal behavior, physiology, and brains-including neurogenesis-change between seasons. We examined seasonal differences in neurogenesis in three brain regions associated with vocal production and learning, HVC (letter-based proper name), robust nucleus of the arcopallium (RA), and Area X, and two brain regions associated with auditory perception, caudomedial nidopallium (NCM) and caudomedial mesopallium (CMM). To do this, we captured wild male and female European starlings (Sturnus vulgaris) in spring and fall, collected a blood sample, and minimized time from capture to tissue collection to limit suppressive effects of captivity on neurogenesis. We quantified neurogenesis using doublecortin (DCX) immunohistochemistry, counting new neurons of three DCX cell morphologies (multipolar, fusiform, and round). We found regional differences in types of morphologies expressed, and amount of neurogenesis across regions: NCM had more fusiform cells than all other regions, and RA had more round cells than other regions. Males had more neurogenesis in HVC in fall than in spring, but there was no seasonal difference in neurogenesis in HVC of females, perhaps reflecting sexually dimorphic vocal learning demands related to repertoire size and complexity. Plasma corticosterone was higher in spring than fall and was correlated with testis volume in males, but it was not correlated with another purported measure of stress, heterophil:lymphocyte ratio (HLR), nor with neurogenesis. Our results suggest that the addition of new neurons to specific regions and circuits may serve different functions for males and females, particularly in the context of vocal production, learning, and perceptual demands across seasons.

Abnormal liver blood tests and liver tumor burden are known prognostic factors in neuroendocrine neoplasms (NEN). However, the relationship between biochemical liver parameters and hepatic tumor load is largely unknown in NEN and in high-grade NEN (G3) specifically. The primary objective of this study was to correlate the biochemical parameters and liver tumor volume of patients with neuroendocrine tumors grade 3 (NET G3) or neuroendocrine carcinomas (NEC). We wanted to investigate whether patients with NET G3 with extensive liver involvement had less severely elevated laboratory liver parameters than NEC patients. In total, 46 patients with NEN were included, 31 had NEC and 15 NET G3. All patients had distant metastatic disease, with liver metastases being the most common (n = 39). Both laboratory results and semiautomatic volumetric measurements of liver tumor burden were obtainable for 34 patients at baseline and 26 patients at follow-up. Alkaline phosphatase (AP), gamma-GT (gGT), and lactate dehydrogenase (LDH) increased significantly between the two time periods (p < .01). In a regression model, liver tumor burden significantly affected several blood parameters, for example, increasing AP, gGT, LDH, and aspartate aminotransferase (ASAT) by a factor of 1.02-1.04 per unit increase (1% tumor burden; all p < .001). AP, gGT, and LDH were significantly lower in NET G3 (factor of 0.43-0.68) than in NEC. Here, we found that liver chemistries changed over the NEN disease course, correlated with hepatic tumor burden, and differed by histologic subtype. The current data can potentially guide treatment decisions, for example, with regard to integration of liver-directed therapies.

Glial cells are an integral component of the nervous system, performing crucial functions that extend beyond structural support, including modulation of the immune system, tissue repair, and maintaining tissue homeostasis. Recent studies have highlighted the importance of glial cells as key mediators of stress responses across different organs. This review focuses on the roles of glial cells in peripheral tissues in health and their involvement in diseases linked to psychological stress. Populations of glia associated with psychological stress ("GAPS") emerge as a promising target cell population in our basic understanding of stress-associated pathologies, highlighting their role as mediators of the deleterious effects of psychological stress on various health conditions. Ultimately, new insights into the impact of stress on glial cell populations in the periphery may support clinical efforts aimed at improving the psychological state of patients for improved health outcomes.

The ongoing production of newborn neurons in the adult hippocampus is reported to be sensitive to perturbations of thyroid hormone signaling, in male rats and mice. Here, we examined whether the neurogenic changes evoked by adult-onset hypothyroidism exhibit sex differences, using male and female C57BL/6N mice. We assessed the impact of goitrogen-induced, adult-onset hypothyroidism on the postmitotic survival and differentiation of hippocampal progenitors in male and female mice. Adult-onset hypothyroidism evoked a significant decline in the postmitotic survival and neuronal differentiation of adult-born progenitors within the dentate gyrus hippocampal subfield of male, but not female, mice. We observed a significant decrease in the number of immature neurons within the hippocampi of adult-onset hypothyroid male mice, whereas adult-onset hypothyroidism evoked by goitrogens using the same treatment paradigms did not evoke any change in immature neuron number in female mice. Gene expression analysis within the hippocampi of euthyroid male and female mice revealed sex-dependent, differential expression of thyroid hormone receptor genes, as well as genes linked to thyroid hormone metabolism and transport. Collectively, our findings highlight sex differences in the influence of goitrogen-induced, adult-onset hypothyroidism on hippocampal neurogenesis, with male, but not female, mice exhibiting a decline in postmitotic hippocampal progenitor survival and neuronal differentiation. These findings underscore the importance of sex as a vital variable when considering the impact of thyroid hormone signaling on the adult hippocampal neurogenic niche.

Stress strongly influences the physiology and behavior of animals, and leads into a pathological condition and disease. NMDA receptors (NMDARs) play a crucial role in the modulation of neural activity. To understand the role of NMDARs in fish stress response, we used NMDARs agonist aspartate to test the functional role of its input on the Dahlgren cell population in the caudal neurosecretory system (CNSS) of the olive flounder. In addition, the effect of the NMDARs antagonist D-AP5 on the expression of genes of the main secretory products of the CNSS after stress was investigated by using qPCR technology and the effect of the NMDARs antagonist D-AP5 on post-stress behavior was explored by behavioral methods. Ex vivo electrophysiological experiments showed that the NMDARs agonist aspartate enhanced the firing frequency of Dahlgren cells. Additionally, aspartate treatment increased the incidence of cells exhibiting bursting firing pattern, this result is corroborated by the observed upregulation in the expression of ion channels and major hormone genes in the CNSS. Furthermore, the excitatory influence of aspartate was effectively counteracted by NMDARs antagonist D-AP5. Interestingly, NMDARs antagonist D-AP5 treatment also significantly decreased the plasma cortisol levels and the expression of CRH, UI, and UII in CNSS after acute stress. Treatment with D-AP5 effectively attenuated the stress response, as evidenced by alterations in respiratory metabolism, sand-burying behavior, swimming distance, simulated capture, and escape response. In conclusion, modulation of Dahlgren cell excitability in the CNSS by NMDARs contributes to the regulation of the stress response, NMDARs antagonist D-AP5 can effectively suppress stress response in flounder by regulating the stress hormone expression and secretion. CLINICAL TRIAL REGISTRATION: Project code SHOU-DW-2022-032.