Neuroendocrine System Research Articles

Apigenin exhibits memory enhancing activity through the restoration of oxido-endocrine balance and upregulation of BDNF/ERK/CREB signalling pathways in stressed mice.

Stress is linked to oxidative imbalance, neuroendocrine system malfunction, and cognitive dysfunction. It is a recognized cause of neuropsychiatric diseases. Natural flavonoid apigenin (API) has neuroprotective and antidepressant properties, but little is known about its potential in restoring memory function under stress-related circumstances. This study investigated the potentials of API administration in abrogating chronic unpredictable mild stress (CUMS)-induced cognitive impairment, including exploring its probable underlying mechanisms in mice. Male mice (n = 10) were treated with API (12.5-25mg/kg, intraperitoneally) 30min before exposure to CUMS daily for 14days. Memory function (Y-maze and novel object recognition test (NOR)) was assessed. Concentrations of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), were estimated using a spectrophotometer. Corticosterone levels were assessed using an enzyme-linked immunosorbent assay (ELISA). Expressions of brain derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase (ERK), and cAMP response element-binding protein (CREB) were assessed using immunohistochemistry. In addition to elevating serum corticosterone and MDA levels, CUMS caused cognitive impairment in mice and decreased GSH, SOD, BDNF, ERK and CREB levels in the prefrontal cortex (PFC) and hippocampus. Administering API restored cognitive function, decreased serum corticosterone and MDA levels, as well as elevated GSH, SOD, BDNF, ERK and CREB levels in the mice brain. The restoration of oxidative, neuroendocrine balance, including upregulating BDNF, CREB, and pERK levels in the brain, all contributed to the neuroprotective effects of API. This suggests that, as shown by the stress paradigm, API may be a promising therapeutic agent for cognitive deficits.

Structural and evolutionary insights into the functioning of glycoprotein hormones and their receptors.

The neuroendocrine system that comprises the glycoprotein hormones (GpHs) and their receptors is essential for reproduction and metabolism. Each GpH hormone is an αβ heterodimer of cystine-knot proteins and its cognate receptor is a G-protein coupled receptor (GPCR) distinguished by a large leucine-rich-repeat (LRR) extracellular domain that binds the hormone and a class A GPCR transmembrane domain that signals through an associating heterotrimeric G protein. Hence, the receptors are called LRR-containing GPCRs-LGRs. The vertebrate GpHs and LGRs have co-evolved from homologs in the earliest metazoan animals, including sponges and comb jellies, but these are absent from unicellular organisms and plants. The two GpH subunits and accompanying LGR receptor of the nematode Caenorhabditis elegans are representative of the invertebrate evolutionary predecessors of human GpH proteins and their receptors, for example follicle-stimulating hormone (FSH) and the FSH receptor (FSHR). Atomic structures of the human GpHs and their receptors, which have been determined by X-ray crystallography and cryogenic electron microscopy (cryo-EM), inform the evolutionary process and provide a mechanistic understanding of the transmission of biochemical signals of hormone binding at the cell surface to the elicitation of second messengers such as cyclic AMP in the cytoplasm. There is compelling biochemical and cellular evidence for the importance of receptor dimers in GpH signaling in cells; yet, all of the human receptors are monomeric as defined beautifully by cryo-EM. Fortunately, the LGR of C. elegans is a stable dimer and its structure, when analyzed in the context of structural information from the human counterparts, predicts a hypothetical model for functionally relevant dimeric associations of the human GpH receptors.

Antimicrobial Neuropeptides and Their Receptors: Immunoregulator and Therapeutic Targets for Immune Disorders

The interaction between the neuroendocrine system and the immune system plays a key role in the onset and progression of various diseases. Neuropeptides, recognized as common biochemical mediators of communication between these systems, are receiving increasing attention because of their potential therapeutic applications in immune-related disorders. Additionally, many neuropeptides share significant similarities with antimicrobial peptides (AMPs), and evidence shows that these antimicrobial neuropeptides are directly involved in innate immunity. This review examines 10 antimicrobial neuropeptides, including pituitary adenylate cyclase-activating polypeptide (PACAP), vasoactive intestinal peptide (VIP), α-melanocyte stimulating hormone (α-MSH), ghrelin, adrenomedullin (AM), neuropeptide Y (NPY), urocortin II (UCN II), calcitonin gene-related peptide (CGRP), substance P (SP), and catestatin (CST). Their expression characteristics and the immunomodulatory mechanisms mediated by their specific receptors are summarized, along with potential drugs targeting these receptors. Future studies should focus on further investigating antimicrobial neuropeptides and advancing the development of related drugs in preclinical and/or clinical studies to improve the treatment of immune-related diseases.

What is known and unknown about the role of neuroendocrine genes Ptprn and Ptprn2

The protein tyrosine phosphatase receptors N and N2 are encoded by the Ptprn and Ptprn2 genes expressed in neuroendocrine cells of the hypothalamus, pituitary gland, and diffuse neuroendocrine system, including the pancreas, lung, and intestine. Unlike other members of the protein tyrosine phosphatase receptor family, PTPRN and PTPRN2 lack protein tyrosine phosphatase activity due to mutation of two residues in their intracellular catalytic domains. However, during evolution these proteins acquired new cellular roles beyond tyrosine dephosphorylation in the centralized and diffuse neuroendocrine systems. Here we discuss the current understanding and lack of information about the actions of these proteins, focusing on neuroendocrine cells of the hypothalamus, pituitary, and pancreas.

Identification of puberty related miRNAs in the hypothalamus of female mice.

Puberty is a crucial developmental stage marked by the transition from childhood to adulthood, organized by complex hormonal signaling within the neuroendocrine system. The hypothalamus, a central region in this system, regulates pubertal functions through the hypothalamic-pituitary-gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH) neurons, essential in puberty control, release GnRH in a pulsatile manner, initiating the production of sex hormones. Major influence in pubertal timing has been attributed to genetic predisposition, environmental factors, and nutritional status. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as key regulators in various cellular processes by either repressing genes or activating them by inhibiting their repressors. The present study aims to investigate the involvement of miRNAs in the control of puberty. Small RNA sequencing was used to identify and compare the total population of miRNAs in the hypothalamus of female mice before, during and after puberty. Bioinformatic analysis was applied to analyse the expression profile of miRNAs with altered levels followed by pathway enrichment analysis. Expression levels of several miRNAs were found up- or down-regulated from pre-pubertal to pubertal stage. Furthermore, monitoring the levels of these miRNAs at the post-pubertal stage revealed four expression patterns, in which pathway analysis displayed the associations of these miRNAs with developmental processes, cell cycle regulation, metabolic biosynthesis and epigenetic regulation. The findings of the present study improve our understanding of the molecular pathways underlying puberty and stress the significance of miRNAs in fine-tuning gene expression within the hypothalamus during this critical developmental stage.

COMPARATIVE CLINICAL EVALUATION OF VAMANA KARMA ALONE AND ALONG WITH PANCHAKOLA PHANTA IN HYPOTHYROIDISM (AGNIMAN-DYA)

Background: The sedentary lifestyle and stress-filled modern era have led to alterations in the activities of the neuro-endocrine system, causing newer health challenges like thyroid disorder. Hypothyroidism is one of the lifestyle and endocrinal disorders. There is no direct reference to the thyroid in Ayurveda classics, but all the metabolic processes of the body are under the control of Agni. Vamana Karma, followed by Panchakola Phanta, can treat Agnimandya. Aim: To compare the efficacy of Vamana Karma alone and along with Panchakola Phanta in Hypothyroidism (Agnimandya). Materials and Methods: A total of 40 patients of Hypothyroidism in the age group of 20 to 60 years fulfilling the inclusion criteria were selected for trial & randomly distributed in Group A and Group B. Results: Statistically, Group B was found more effective than Group A in the management of symptoms of Hypothyroidism (Agnimandya). Discussion: Panchakola having Ushna, Tikshna, Laghu, Ruksha Guna, Katu Rasa, Katu Vipaka and Ushna Virya. It has Kaphavata Shamaka, Deepana, Pachana, Rochana, Lekhana, Sroto-Vishodhana and Shothahara properties. Panchakola is regarded as one of the most effective medications for treating Mandagni. In Agnimandya, Panchakola Phanta is useful for Amapachana and to increase the Agni.

A narrative review of exercise intervention mechanisms for post-traumatic stress disorder in veterans.

Post-traumatic stress disorder (PTSD) severely disrupts the daily lives of veterans and active duty personnel and may influence their suicidal behaviour. This study provides insight into existing research on PTSD in veterans through a narrative review. Exercise was found to reduce PTSD symptoms in veterans at both psychological and physiological levels, which in turn inhibits their suicidal tendencies. At the psychological level, exercise improved veterans' Subjective Well-Being and Psychological Well-Being, and at the physiological level, it improved veterans' brain structure, neuroendocrine system, and immune system. By combing these mechanisms in detail, we hope to provide theoretical support for the implementation of exercise interventions in the treatment of veterans with PTSD. However, it is important to note that the specifics of the exercise program, such as the optimal type, dosage, and duration to alleviate PTSD symptoms, remain unclear and require further research and exploration.

Repeated Amphetamine Exposure Blunted Angiotensin II-Induced Responses Mediated by AT1 Receptors.

Angiotensin II, is critical in regulating the sympathetic and neuroendocrine systems through angiotensin II type 1 receptors (AT1-R). Angiotensin II intracerebral administration increases water and sodium intake, as well as renal sodium excretion. Previously, our group has shown that AT1-R is involved in behavioral and neurochemical sensitization induced by amphetamine. We aimed to assess the physiological output, behavioral, and neurochemical responses to intracerebral angiotensin II administration, via the AT1-R, twenty-one days after amphetamine administration. Male Wistar rats received daily vehicle or AT1-R antagonist (oral) for 10 days, and amphetamine or saline intraperitoneal (i.p.) from day 6 to 10. On day 25 they were implanted with an intracerebral cannula. On day 32, the animals received intracerebral angiotensin II. First group: the animals were tested in a free choice paradigm for 2% NaCl and water intake, and sacrificed for neuronal activity assessment via c-Fos immunohistochemistry. Second group: urine samples were collected for electrolyte determination. Third group: the animals were tested in the plus maze or the hole board for anxiety and working memory evaluation, respectively, and sacrificed for c-Fos immunohistochemistry. Amphetamine exposure blunted the increase in sodium intake (p = 0.0022), and potentiated the natriuretic (p = 0.0043) and kaliuretic effect (p = 0.0002) induced by angiotensin II. Moreover, amphetamine exposure prevented the expression of the anxiogenic effect (drug effect p < 0.0001) and the memory deficit (p = 0.1314) induced by cerebral angiotensin II administration. Amph decreased c-Fos immunoreactivity in nucleus tractus solitarii (NTS) p = 0.0037; paraventricular nucleus (PVN) p = 0.0047; Central amygdala (CeA) p = 0.0008; Basolateral amygdala (BLA) p = 0.0018; increased in hippocampus region CA1 p = 0.0043; CA3 p = 0.026; and dentate gyrus (DG) p = 0.0057. The blockade of AT1-R prevented these alterations (sodium intake p = 0.0421 natriuresis p = 0.019; kaliuresis p = 0.196; working memory (p < 0.0001); but no the anxiogenic response to angiotensin II (drug effect p < 0.0001); as well as the c-Fos changes (NTS p = 0.0052; PVN p = 0.029; CeA p = 0.0002; BLA p = 0.0021; CA1 p = 0.0026; CA3 p = 0.022; and DG p = 0.0016). Most of the long-lasting AT1-R altered responses to brain angiotensin II administration induced by repeated amphetamine exposure could be prevented by AT1-R blockade.

Distribution of the kisspeptin system and its relation with gonadotropin-releasing hormone in the hypothalamus.

Kisspeptin (KISS1), originally catalogued as metastin because of its capacity as a metastasis suppressor in human melanoma and breast cancer, is now recognized as the major puberty gatekeeper and gonadotropin-releasing hormone (GnRH) neuroendocrine system modulator. It is a member of the family of RFamide-related peptidesthat also includes the neuropeptide FF group, the gonadotropin-inhibitory hormone, the prolactin-releasing peptide, and the 26RFa peptides. The KISS1 precursor peptide is processed into a family of peptides known as kisspeptins. Its expression has been described in the hypothalamus as well as in the whole reproductive axis and several extra reproductive tissues of mammals as well as fish and amphibians, but not in birds. KISS1 plays an essential role as a regulator of the reproductive axis by inducing the synthesis and release of GnRH, acting through specific receptors. The study of the kisspeptin system and its relation with reproduction in wild and non-classical laboratory species is extremely useful to understand and become aware of the role of KISS1 in the wide variety of possible different reproductive strategies. In this chapter, KISS1 involvement in non-classical laboratory rodents, fishes, and birds is discussed.

Effects of Stress Induced Neuroendocrine Immune Interaction on Periodontium A Review

This review discusses recent advances in our understanding of the relationships between psychological stress neuroendocrine immune system and periodontitis including how host stress responses affect immune function alter the oral microbiome and biofilm formation and promote disease progression

Aphrodisiac Activity of The n-Hexane Fraction of Clove Leaves (Syzygium aromaticum L.) on The Fertility of Male White Rats (Rattus norvegicus)

Aphrodisiacs are stimulant that modulate the neuroendocrine system to enhance libido or sexual desire and affect reproductive activity. Hormonal or neurological imbalances, as well as disruptions in reproductive tissue, can affect male fertility. One plant known to stimulate sexual arousal is the clove (Syzygium aromaticum L.), with its active compound, primarily eugenol, presumed to enhance testicular function and thereby potentially address male sexual dysfunction. This study aims to examine the aphrodisiac activity of the n-hexane fraction of clove leaves (Syzygium aromaticum L.) on the fertility of male white rats by assessing parameters such as the mating index, fertility index, libido index, pregnancy index, and live fetus index. This research used an experimental method with a post-test modified randomized control group design, involving 20 male and 40 female white rats divided into four treatment groups in a 1:2 ratio. Each group comprised 5 male and 10 female rats. The groups included a normal control (Na-CMC), a positive control (X-Gra 51.37 mg/kg BW), a clove leaf extract group (250 mg/kg BW), and an n-hexane fraction of clove leaves group (250 mg/kg BW). The findings indicate that the n-hexane fraction of clove leaves (Syzygium aromaticum L.) at a dose of 250 mg/kg BW contains secondary metabolite steroids and exhibits significant aphrodisiac activity that affect fertility which is characterized by a significant differences in the percentages of pregnancy and fertility indices.

Mild Gestational Hypothyroidism in Mice Has Transient Developmental Effects and Long-Term Consequences on Neuroendocrine Systems.

Background: Thyroid hormones (TH) play a key role in fetal brain development. While severe thyroid dysfunction, has been shown to cause neurodevelopmental and reproductive disorders, the rising levels of TH-disruptors in the environment in the past few decades have increased the need to assess effects of subclinical (mild) TH insufficiency during gestation. Since embryos do not produce their own TH before mid-gestation, early development processes rely on maternal production. Notably, the reproductive network governed by gonadotropin-releasing hormone (GnRH) neurons develops during this critical period. Methods: The risk of mild maternal hypothyroidism on the development of GnRH neurons and long-term effect on neuroendocrine function in the offspring was investigated using a mouse model of gestational hypothyroidism induced by methimazole (MMI) treatment. Results: MMI treatment during gestation led to reduced litter size, consistent with increased miscarriages due to hypothyroidism. E12/13 embryos, collected from MMI-treated dams, had a decreased number of GnRH neurons, but the migration of the remaining GnRH neurons was normal. Cell proliferation was reduced in the vomeronasal organ (VNO), correlating with the reduced number of GnRH neurons detected in this region. Using a GnRH cell line confirmed attenuated proliferation in the absence of T3. Pups born from hypothyroid mothers had normal postweaning growth and estrus cycles, yet adult offspring had significantly more cells expressing estrogen receptor alpha in the arcuate nucleus. Notably, by adulthood, GnRH cell number and distribution was comparable with nontreated controls indicating that compensatory mechanisms occurred after E13. Conclusion: Overall, our work shows that mild TH disruption during gestation transiently affects proliferation of the pool of GnRH neurons within the VNO and has a long-term impact on neuroendocrine systems.

To be or not to be manipulated by our bacteria?

The gut microbiota has become a central focus of research since its intricate connection with the brain was identified. Notably, the gut microbiota can influence mental health, opening new prospects for improving the management of psychiatric disorders. Understanding the bidirectional interactions between the brain, gut, and microbiome is crucial for evaluating the true impact of gut microbiota on mental health and its subsequent implications for psychiatry. Currently, the brain-gut-microbiome axis communicates through five interconnected pathways: the immune system, the vagus nerve, the enteric nervous system, the neuroendocrine system, and the circulatory system. The development of microbiota-based therapeutics signals significant changes in current clinical practices. Furthermore, microbiome-based therapeutics are expected to undergo substantial regulatory transformations in Europe in the coming years. This mini-review aims to explore these aspects to evaluate the potential of gut bacteria to shape mental health interventions.

Azadirachtin disrupts ecdysone signaling and alters sand fly immunity

BackgroundLeishmaniasis is a group of neglected vector-borne diseases transmitted by phlebotomine sand flies. Leishmania parasites must overcome various defenses in the sand fly midgut, including the insects’s immune response. Insect immunity is regulated by the ecdysone hormone, which binds to its nuclear receptor (EcR) and activates the transcription of genes involved in insect immunity. However, the role of ecdysone in sand fly immunity has never been studied. Phlebotomus perniciosus is a natural vector of Leishmania infantum; here, we manipulated its neuroendocrine system using azadirachtin (Aza), a natural compound known to affect ecdysone synthesis.MethodsPhlebotomus perniciosus larvae and adult females were fed on food containing either Aza alone or Aza plus ecdysone, and the effects on mortality and ecdysis were evaluated. Genes related to ecdysone signaling and immunity were identified in P. perniciosus, and the expression of antimicrobial peptides (AMPs), EcR, the ecdysone-induced genes Eip74EF and Eip75B, and the transcription factor serpent were analyzed using quantitative polymerase chain reaction (PCR).ResultsAza treatment inhibited molting of first-instar (L1) larvae to L2, with only 10% of larvae molting compared to 95% in the control group. Serpent and Eip74EF, attacin, defensin 1, and defensin 2 genes were downregulated by Aza treatment in larvae. Similarly, Aza-treated adult females also presented suppression of ecdysone signaling-related genes and the AMPs attacin and defensin 2. Notably, all gene repression caused by Aza was reversed by adding ecdysone concomitantly with Aza to the larval or female food, indicating that these genes are effective markers for ecdysone repression.ConclusionsThese results highlight the critical role of ecdysone in regulating the development and immunity of P. perniciosus, which potentially could interfere with Leishmania infection.Graphical

ЛЕЧЕБНО-ВОССТАНОВИТЕЛЬНЫЕ И БИОТЕХНОЛОГИЧЕСКИЕ РЕСУРСЫ НАУЧНОЙ МУЗЫКОТЕРАПИИ В РЕШЕНИИ ПРОБЛЕМ БЕСПЛОДИЯ

Scientific music therapy is an advanced therapeutic and preventive direction, widely in demand in various areas of health care, psychological assistance, and social rehabilitation, but still underestimated in reproductive medicine. Complex scientific research conducted over thirty years has helped to better understand the nature of the main mechanisms of music's influence on the neuroendocrine system, vital organs, and cellular structures. On this basis, unique and effective methods of scientific music therapy and promising biotechnologies have been created, the possibilities of which in solving infertility problems are discussed in this article.

Immunomodulatory Properties of Multi-Strain Postbiotics on Human CD14+ Monocytes.

The ability of probiotics, comprising live microbiota, to modulate the composition of intestinal microbiomes has been connected to modulation of the central nervous system (Gut-Brain axis), neuroendocrine system (Gut-Skin axis), and immune response (Gut-Immune axis). Less information is known regarding the ability of postbiotics (cell wall components and secreted metabolites derived from live organisms) to regulate host immunity. In the present study, we tested postbiotics comprising single strains of bacteria and yeast (Lactobacillus acidophilus 16axg, Lacticaseibacillus rhamnosus 18fx, Saccharomyces cerevisiae var. boulardii 16mxg) as well as combinations of multiple strains for their ability to stimulate cytokine production by human CD14+ monocytes. We quantified cytokine gene and protein expression levels in monocytes following stimulation with postbiotics. Both heat-killed L. acidophilus and L. rhamnosus stimulated naïve monocytes without significant differences between them. Heat-killed S. boulardii stimulated less cytokine production compared to postbiotic bacteria at the same concentration. Interestingly, the addition of heat-killed yeast to heat-killed L. acidophilus and L. rhamnosus resulted in an enhancement of immune stimulation. Thus, heat-killed postbiotics have immune-modulating potential, particularly when bacteria and yeast are combined. This approach may hold promise for developing targeted interventions that can be fine-tuned to modulate host immune response with beneficial health impact.

Спорадическая медуллярная карцинома щитовидной железы в детском возрасте: клиническое наблюдение

Medullary thyroid carcinoma (MTC) is one of the rarest tumors of the neuroendocrine system occurring in childhood. MTC represents approximately 4% to 8% of all thyroid malignancies in children with an incidence of 0.03 per 100,000 pediatric population per annum. As a rule, MCT in childhood is presented as part of hereditary syndromes (MEN2A, MEN2B) whereas the prevalence of the sporadic form has not been sufficiently studied as well as its molecular and genetic features. Authors represent the Russia’s first clinical case of sporadic MTC in a 16 years old child. The girl at the age of 14 y/o was examined by an endocrinologist at the place of residence due to the absence of menarche. According to the results of a comprehensive examination, a mass measuring of up to 27 mm was detected in the left lobe of the thyroid gland. Cytological examination revealed a picture suspicious for C-cell carcinoma. The basal calcitonin level was 2160 pg/ml (with 0 to 4.8 pg/ml as a norm). The patient had then underwent thyroidectomy with central lymphadenectomy as a result of histological and immunohistochemical studies of medullary thyroid carcinoma pT2N0 MxLV0Pn0. According to the results of molecular genetic study of peripheral blood, neither germinal pathogenic nor opportunistic mutations in RET gene were detected. Full-exome sequencing of DNA isolated from tumour tissue revealed as pathogenic/conditional pathogenic mutations RET p.M918T, CHEK2 p. R29X, VRK1 p.H119R and ARSE p. G422R. After 3.5 years of follow-up, the patient had a complete structural and biochemical remission of the disease.

A New Insight into the Mechanism of Atrazine-Induced Neurotoxicity: Triggering Neural Stem Cell Senescence by Activating the Integrated Stress Response Pathway.

Atrazine (AT), a widely utilized chemical herbicide, causes widespread contamination of agricultural water bodies. Recently, exposure to AT has been linked to the development of age-related neurodegenerative diseases (NDs), suggesting its neurotoxicity potential. As an endocrine disruptor, AT targets the hypothalamus, a crucial part of the neuroendocrine system. However, the toxicological mechanism of AT exposure to the hypothalamus and its correlation with ND development remain unexplored. Our results indicated that AT exposure caused significant morphological and structural damage to the hypothalamus, leading to the loss of mature and intact neurons and microglial activation. Furthermore, hypothalamic neural stem cells (HtNSCs) were recruited to areas of neuronal damage caused by AT. Through invivo and invitro experiments, we clarified the outcomes of AT-induced HtNSC recruitment alongside the loss of mature/intact neurons. Mechanistically, AT induces senescence in these recruited HtNSCs by activating integrated stress response signaling. This consequently hinders the repair of damaged neurons by inhibiting HtNSC proliferation and differentiation. Overall, our findings underscore the pivotal role of the integrated stress response pathway in AT-induced HtNSC senescence and hypothalamic damage. Additionally, the present study offers novel perspectives to understand the mechanisms of AT-induced neurotoxicity and provides preliminary evidence linking AT contamination to the development of NDs.

Integrated Analysis of Neuroendocrine and Neurotransmission Pathways Following Developmental Atrazine Exposure in Zebrafish.

Atrazine is an endocrine-disrupting herbicide, with exposure impacting adverse outcomes along multiple endocrine pathways. This study investigated the neuroendocrine system as the central target of atrazine toxicity, examining effects of early developmental exposures on neurohormones and genes associated with kisspeptin, hypothalamic, pituitary, and dopamine systems. Zebrafish were exposed to 0, 0.3, 3, or 30 ppb (µg/L) atrazine during two developmental time windows. For neurohormone assessments, exposure was ceased at the end of embryogenesis (72 h post-fertilization, hpf) and analyzed immediately or grown to 0.5, 2, or 2.5 years post-fertilization (ypf). Gene expression was measured immediately after 1-72 hpf or 72-120 hpf exposure. Estradiol decreased in the 0.3 and 30 ppb groups in 0.5 ypf female brains, while dopamine decreased in the same treatment groups at 72 hpf. Increases were also observed in 2.5 ypf female brains (3 ppb) for estradiol and in 2 ypf female and male brains (3 and 30 ppb) for dopamine. Gene expression alterations occurred for the follicle-stimulating hormone (fsh) at 72 hpf and the growth hormone (gh1) at 72 and 120 hpf. Overall, results indicated that developmental atrazine exposure has immediate and long-term sex-specific effects on neurohormonal systems.

Transcriptome Reveals Molecular Mechanisms of Neuroendocrine Regulation of Allometric Growth in the Red Swamp Crayfish Procambarus clarkii.

Allometric growth is a typical characteristic of crustaceans, which mainly occurs among individuals, life stages, tissues, and between sexes. The red swamp crayfish Procambarus clarkii is an economically important crustacean species in the world. To date, the molecular regulatory mechanisms of neuroendocrine system in the allometric growth of P. clarkii remain unclear. In this study, P. clarkii exhibiting significant allometric growth among individuals were sampled from three full-sibling families. The brain, eyestalk, nerve cord, and Y-organ were dissected for transcriptome analysis. Key functional genes were identified by random forest and DESeq2 methods. The gene pathways were enriched utilizing Kyoto Encyclopedia Genes and Genomes (KEGG) analysis. Gene topological analysis was established through weighted gene co-expression network analysis (WGCNA), and hub genes were screened by protein-protein interaction (PPI) networks. Transcriptomic analysis results were validated via qRT-PCR. RNA-Seq identified 31 differentially expressed genes (DEGs) (7 up- and 24 downregulated); 301 DEGs (23 up- and 278 downregulated); 1308 DEGs (474 up- and 834 downregulated); and 64 DEGs (52 up- and 12 downregulated) in the brain, eyestalk, Y-organ, and nerve cord, respectively. Crucial functional genes such as CHIA in the brain and perlucin-like in the eyestalk were notably identified. WGCNA revealed two hub modules, while PPI networks identified neuroendocrine regulators module which hub genes mainly including CP1876-like and cuticle protein AM1199-like, and structural components module which hub genes mainly including CUB& CCP Domain-Containing Protein, ARRDC, and E3 Ubiquitin protein ligase MCYCBP2-like. Correspondingly, the significant gene pathways such as amino sugar and nucleotide sugar metabolism (pcla00520) and insect hormone biosynthesis (pcla00981) were enriched. The results revealed the complex interactions and regulatory relationships of hub genes within hub modules to coordinate molting and growth. The results of RNA-Seq analysis were validated by the consistency of gene expression in qRT-PCR. In present study, key functional genes in the neuroendocrine system regulating allometric growth among individuals were identified, and significant pathways mainly include hormone synthesis were screened, thus constructing a neuroendocrine molecular regulatory network for the allometric growth of P. clarkii. Building on these investigations, a comprehensive mechanism whereby neuroendocrine regulators interact with structural components to coordinate molting and growth was proposed. The result would provide valuable insights into the molecular regulatory mechanisms of allometric growth, highlighting the interplay between the neuroendocrine system and relevant tissues.