Displaying publications 41 - 60 of 80 in total

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  1. Raes N, Cannon CH, Hijmans RJ, Piessens T, Saw LG, van Welzen PC, et al.
    Proc Natl Acad Sci U S A, 2014 Nov 25;111(47):16790-5.
    PMID: 25385612 DOI: 10.1073/pnas.1403053111
    The extent of Dipterocarp rainforests on the emergent Sundaland landmass in Southeast Asia during Quaternary glaciations remains a key question. A better understanding of the biogeographic history of Sundaland could help explain current patterns of biodiversity and support the development of effective forest conservation strategies. Dipterocarpaceae trees dominate the rainforests of Sundaland, and their distributions serve as a proxy for rainforest extent. We used species distribution models (SDMs) of 317 Dipterocarp species to estimate the geographic extent of appropriate climatic conditions for rainforest on Sundaland at the last glacial maximum (LGM). The SDMs suggest that the climate of central Sundaland at the LGM was suitable to sustain Dipterocarp rainforest, and that the presence of a previously suggested transequatorial savannah corridor at that time is unlikely. Our findings are supported by palynologic evidence, dynamic vegetation models, extant mammal and termite communities, vascular plant fatty acid stable isotopic compositions, and stable carbon isotopic compositions of cave guano profiles. Although Dipterocarp species richness was generally lower at the LGM, areas of high species richness were mostly found off the current islands and on the emergent Sunda Shelf, indicating substantial species migration and mixing during the transitions between the Quaternary glacial maxima and warm periods such as the present.
  2. Ariffin H, Hainaut P, Puzio-Kuter A, Choong SS, Chan AS, Tolkunov D, et al.
    Proc Natl Acad Sci U S A, 2014 Oct 28;111(43):15497-501.
    PMID: 25313051 DOI: 10.1073/pnas.1417322111
    The Li-Fraumeni syndrome (LFS) and its variant form (LFL) is a familial predisposition to multiple forms of childhood, adolescent, and adult cancers associated with germ-line mutation in the TP53 tumor suppressor gene. Individual disparities in tumor patterns are compounded by acceleration of cancer onset with successive generations. It has been suggested that this apparent anticipation pattern may result from germ-line genomic instability in TP53 mutation carriers, causing increased DNA copy-number variations (CNVs) with successive generations. To address the genetic basis of phenotypic disparities of LFS/LFL, we performed whole-genome sequencing (WGS) of 13 subjects from two generations of an LFS kindred. Neither de novo CNV nor significant difference in total CNV was detected in relation with successive generations or with age at cancer onset. These observations were consistent with an experimental mouse model system showing that trp53 deficiency in the germ line of father or mother did not increase CNV occurrence in the offspring. On the other hand, individual records on 1,771 TP53 mutation carriers from 294 pedigrees were compiled to assess genetic anticipation patterns (International Agency for Research on Cancer TP53 database). No strictly defined anticipation pattern was observed. Rather, in multigeneration families, cancer onset was delayed in older compared with recent generations. These observations support an alternative model for apparent anticipation in which rare variants from noncarrier parents may attenuate constitutive resistance to tumorigenesis in the offspring of TP53 mutation carriers with late cancer onset.
  3. Troell M, Naylor RL, Metian M, Beveridge M, Tyedmers PH, Folke C, et al.
    Proc Natl Acad Sci U S A, 2014 Sep 16;111(37):13257-63.
    PMID: 25136111 DOI: 10.1073/pnas.1404067111
    Aquaculture is the fastest growing food sector and continues to expand alongside terrestrial crop and livestock production. Using portfolio theory as a conceptual framework, we explore how current interconnections between the aquaculture, crop, livestock, and fisheries sectors act as an impediment to, or an opportunity for, enhanced resilience in the global food system given increased resource scarcity and climate change. Aquaculture can potentially enhance resilience through improved resource use efficiencies and increased diversification of farmed species, locales of production, and feeding strategies. However, aquaculture's reliance on terrestrial crops and wild fish for feeds, its dependence on freshwater and land for culture sites, and its broad array of environmental impacts diminishes its ability to add resilience. Feeds for livestock and farmed fish that are fed rely largely on the same crops, although the fraction destined for aquaculture is presently small (∼4%). As demand for high-value fed aquaculture products grows, competition for these crops will also rise, as will the demand for wild fish as feed inputs. Many of these crops and forage fish are also consumed directly by humans and provide essential nutrition for low-income households. Their rising use in aquafeeds has the potential to increase price levels and volatility, worsening food insecurity among the most vulnerable populations. Although the diversification of global food production systems that includes aquaculture offers promise for enhanced resilience, such promise will not be realized if government policies fail to provide adequate incentives for resource efficiency, equity, and environmental protection.
  4. Vincent JR, Carson RT, DeShazo JR, Schwabe KA, Ahmad I, Chong SK, et al.
    Proc Natl Acad Sci U S A, 2014 Jul 15;111(28):10113-8.
    PMID: 24982171 DOI: 10.1073/pnas.1312246111
    Inadequate funding from developed countries has hampered international efforts to conserve biodiversity in tropical forests. We present two complementary research approaches that reveal a significant increase in public demand for conservation within tropical developing countries as those countries reach upper-middle-income (UMI) status. We highlight UMI tropical countries because they contain nearly four-fifths of tropical primary forests, which are rich in biodiversity and stored carbon. The first approach is a set of statistical analyses of various cross-country conservation indicators, which suggests that protective government policies have lagged behind the increase in public demand in these countries. The second approach is a case study from Malaysia, which reveals in a more integrated fashion the linkages from rising household income to increased household willingness to pay for conservation, nongovernmental organization activity, and delayed government action. Our findings suggest that domestic funding in UMI tropical countries can play a larger role in (i) closing the funding gap for tropical forest conservation, and (ii) paying for supplementary conservation actions linked to international payments for reduced greenhouse gas emissions from deforestation and forest degradation in tropical countries.
  5. Ogawa S, Nathan FM, Parhar IS
    Proc Natl Acad Sci U S A, 2014 Mar 11;111(10):3841-6.
    PMID: 24567386 DOI: 10.1073/pnas.1314184111
    Kisspeptin, a neuropeptide encoded by the KISS1/Kiss1, and its cognate G protein-coupled receptor, GPR54 (kisspeptin receptor, Kiss-R), are critical for the control of reproduction in vertebrates. We have previously identified two kisspeptin genes (kiss1 and kiss2) in the zebrafish, of which kiss1 neurons are located in the habenula, which project to the median raphe. kiss2 neurons are located in the hypothalamic nucleus and send axonal projections to gonadotropin-releasing hormone neurons and regulate reproductive functions. However, the physiological significance of the Kiss1 expressed in the habenula remains unknown. Here we demonstrate the role of habenular Kiss1 in alarm substance (AS)-induced fear response in the zebrafish. We found that AS-evoked fear experience significantly reduces kiss1 and serotonin-related genes (plasmacytoma expressed transcript 1 and solute carrier family 6, member 4) in the zebrafish. Furthermore, Kiss1 administration suppressed the AS-evoked fear response. To further evaluate the role of Kiss1 in fear response, zebrafish Kiss1 peptide was conjugated to saporin (SAP) to selectively inactivate Kiss-R1-expressing neurons. The Kiss1-SAP injection significantly reduced Kiss1 immunoreactivity and c-fos mRNA in the habenula and the raphe compared with control. Furthermore, 3 d after Kiss1-SAP injection, the fish had a significantly reduced AS-evoked fear response. These findings provide an insight into the role of the habenular kisspeptin system in inhibiting fear.
  6. Nikolov LA, Endress PK, Sugumaran M, Sasirat S, Vessabutr S, Kramer EM, et al.
    Proc Natl Acad Sci U S A, 2013 Nov 12;110(46):18578-83.
    PMID: 24167265 DOI: 10.1073/pnas.1310356110
    Rafflesiaceae, which produce the world's largest flowers, have captivated the attention of biologists for nearly two centuries. Despite their fame, however, the developmental nature of the floral organs in these giants has remained a mystery. Most members of the family have a large floral chamber defined by a diaphragm. The diaphragm encloses the reproductive organs where pollination by carrion flies occurs. In lieu of a functional genetic system to investigate floral development in these highly specialized holoparasites, we used comparative studies of structure, development, and gene-expression patterns to investigate the homology of their floral organs. Our results surprisingly demonstrate that the otherwise similar floral chambers in two Rafflesiaceae subclades, Rafflesia and Sapria, are constructed very differently. In Rafflesia, the diaphragm is derived from the petal whorl. In contrast, in Sapria it is derived from elaboration of a unique ring structure located between the perianth and the stamen whorl, which, although developed to varying degrees among the genera, appears to be a synapomorphy of the Rafflesiaceae. Thus, the characteristic features that define the floral chamber in these closely related genera are not homologous. These differences refute the prevailing hypothesis that similarities between Sapria and Rafflesia are ancestral in the family. Instead, our data indicate that Rafflesia-like and Sapria-like floral chambers represent two distinct derivations of this morphology. The developmental repatterning we identified in Rafflesia, in particular, may have provided architectural reinforcement, which permitted the explosive growth in floral diameter that has arisen secondarily within this subclade.
  7. Lee SH, Wong RR, Chin CY, Lim TY, Eng SA, Kong C, et al.
    Proc Natl Acad Sci U S A, 2013 Sep 10;110(37):15067-72.
    PMID: 23980181 DOI: 10.1073/pnas.1311725110
    Burkholderia pseudomallei is a Gram-negative soil bacterium that infects both humans and animals. Although cell culture studies have revealed significant insights into factors contributing to virulence and host defense, the interactions between this pathogen and its intact host remain to be elucidated. To gain insights into the host defense responses to B. pseudomallei infection within an intact host, we analyzed the genome-wide transcriptome of infected Caenorhabditis elegans and identified ∼6% of the nematode genes that were significantly altered over a 12-h course of infection. An unexpected feature of the transcriptional response to B. pseudomallei was a progressive increase in the proportion of down-regulated genes, of which ELT-2 transcriptional targets were significantly enriched. ELT-2 is an intestinal GATA transcription factor with a conserved role in immune responses. We demonstrate that B. pseudomallei down-regulation of ELT-2 targets is associated with degradation of ELT-2 protein by the host ubiquitin-proteasome system. Degradation of ELT-2 requires the B. pseudomallei type III secretion system. Together, our studies using an intact host provide evidence for pathogen-mediated host immune suppression through the destruction of a host transcription factor.
  8. Hall SJ, Hilborn R, Andrew NL, Allison EH
    Proc Natl Acad Sci U S A, 2013 May 21;110(21):8393-8.
    PMID: 23671089 DOI: 10.1073/pnas.1208067110
    This article examines two strands of discourse on wild capture fisheries; one that focuses on resource sustainability and environmental impacts, another related to food and nutrition security and human well-being. Available data and research show that, for countries most dependent on fish to meet the nutritional requirements of their population, wild capture fisheries remain the dominant supplier. Although, contrary to popular narratives, the sustainability of these fisheries is not always and everywhere in crisis, securing their sustainability is essential and requires considerable effort across a broad spectrum of fishery systems. An impediment to achieving this is that the current research and policy discourses on environmental sustainability of fisheries and food security remain only loosely and superficially linked. Overcoming this requires adoption of a broader sustainability science paradigm to help harness synergies and negotiate tradeoffs between food security, resource conservation, and macroeconomic development goals. The way society chooses to govern fisheries is, however, an ethical choice, not just a technical one, and we recommend adding an ethical dimension to sustainability science as applied to fisheries.
  9. Moon RW, Sharaf H, Hastings CH, Ho YS, Nair MB, Rchiad Z, et al.
    Proc Natl Acad Sci U S A, 2016 Jun 28;113(26):7231-6.
    PMID: 27303038 DOI: 10.1073/pnas.1522469113
    The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.
  10. Richards DR, Friess DA
    Proc Natl Acad Sci U S A, 2016 Jan 12;113(2):344-9.
    PMID: 26712025 DOI: 10.1073/pnas.1510272113
    The mangrove forests of Southeast Asia are highly biodiverse and provide multiple ecosystem services upon which millions of people depend. Mangroves enhance fisheries and coastal protection, and store among the highest densities of carbon of any ecosystem globally. Mangrove forests have experienced extensive deforestation owing to global demand for commodities, and previous studies have identified the expansion of aquaculture as largely responsible. The proportional conversion of mangroves to different land use types has not been systematically quantified across Southeast Asia, however, particularly in recent years. In this study we apply a combined geographic information system and remote sensing method to quantify the key proximate drivers (i.e., replacement land uses) of mangrove deforestation in Southeast Asia between 2000 and 2012. Mangrove forests were lost at an average rate of 0.18% per year, which is lower than previously published estimates. In total, more than 100,000 ha of mangroves were removed during the study period, with aquaculture accounting for 30% of this total forest change. The rapid expansion of rice agriculture in Myanmar, and the sustained conversion of mangroves to oil palm plantations in Malaysia and Indonesia, are identified as additional increasing and under-recognized threats to mangrove ecosystems. Our study highlights frontiers of mangrove deforestation in the border states of Myanmar, on Borneo, and in Indonesian Papua. To implement policies that conserve mangrove forests across Southeast Asia, it is essential to consider the national and subnational variation in the land uses that follow deforestation.
  11. Navarro MA, Atlas EL, Saiz-Lopez A, Rodriguez-Lloveras X, Kinnison DE, Lamarque JF, et al.
    Proc Natl Acad Sci U S A, 2015 Nov 10;112(45):13789-93.
    PMID: 26504212 DOI: 10.1073/pnas.1511463112
    Very short-lived brominated substances (VSLBr) are an important source of stratospheric bromine, an effective ozone destruction catalyst. However, the accurate estimation of the organic and inorganic partitioning of bromine and the input to the stratosphere remains uncertain. Here, we report near-tropopause measurements of organic brominated substances found over the tropical Pacific during the NASA Airborne Tropical Tropopause Experiment campaigns. We combine aircraft observations and a chemistry-climate model to quantify the total bromine loading injected to the stratosphere. Surprisingly, despite differences in vertical transport between the Eastern and Western Pacific, VSLBr (organic + inorganic) contribute approximately similar amounts of bromine [∼6 (4-9) parts per trillion] [corrected] to the stratospheric input at the tropical tropopause. These levels of bromine cause substantial ozone depletion in the lower stratosphere, and any increases in future abundances (e.g., as a result of aquaculture) will lead to larger depletions.
  12. Assefa S, Lim C, Preston MD, Duffy CW, Nair MB, Adroub SA, et al.
    Proc Natl Acad Sci U S A, 2015 Oct 20;112(42):13027-32.
    PMID: 26438871 DOI: 10.1073/pnas.1509534112
    Malaria cases caused by the zoonotic parasite Plasmodium knowlesi are being increasingly reported throughout Southeast Asia and in travelers returning from the region. To test for evidence of signatures of selection or unusual population structure in this parasite, we surveyed genome sequence diversity in 48 clinical isolates recently sampled from Malaysian Borneo and in five lines maintained in laboratory rhesus macaques after isolation in the 1960s from Peninsular Malaysia and the Philippines. Overall genomewide nucleotide diversity (π = 6.03 × 10(-3)) was much higher than has been seen in worldwide samples of either of the major endemic malaria parasite species Plasmodium falciparum and Plasmodium vivax. A remarkable substructure is revealed within P. knowlesi, consisting of two major sympatric clusters of the clinical isolates and a third cluster comprising the laboratory isolates. There was deep differentiation between the two clusters of clinical isolates [mean genomewide fixation index (FST) = 0.21, with 9,293 SNPs having fixed differences of FST = 1.0]. This differentiation showed marked heterogeneity across the genome, with mean FST values of different chromosomes ranging from 0.08 to 0.34 and with further significant variation across regions within several chromosomes. Analysis of the largest cluster (cluster 1, 38 isolates) indicated long-term population growth, with negatively skewed allele frequency distributions (genomewide average Tajima's D = -1.35). Against this background there was evidence of balancing selection on particular genes, including the circumsporozoite protein (csp) gene, which had the top Tajima's D value (1.57), and scans of haplotype homozygosity implicate several genomic regions as being under recent positive selection.
  13. van Panhuis WG, Choisy M, Xiong X, Chok NS, Akarasewi P, Iamsirithaworn S, et al.
    Proc Natl Acad Sci U S A, 2015 Oct 20;112(42):13069-74.
    PMID: 26438851 DOI: 10.1073/pnas.1501375112
    Dengue is a mosquito-transmitted virus infection that causes epidemics of febrile illness and hemorrhagic fever across the tropics and subtropics worldwide. Annual epidemics are commonly observed, but there is substantial spatiotemporal heterogeneity in intensity. A better understanding of this heterogeneity in dengue transmission could lead to improved epidemic prediction and disease control. Time series decomposition methods enable the isolation and study of temporal epidemic dynamics with a specific periodicity (e.g., annual cycles related to climatic drivers and multiannual cycles caused by dynamics in population immunity). We collected and analyzed up to 18 y of monthly dengue surveillance reports on a total of 3.5 million reported dengue cases from 273 provinces in eight countries in Southeast Asia, covering ∼ 10(7) km(2). We detected strong patterns of synchronous dengue transmission across the entire region, most markedly during a period of high incidence in 1997-1998, which was followed by a period of extremely low incidence in 2001-2002. This synchrony in dengue incidence coincided with elevated temperatures throughout the region in 1997-1998 and the strongest El Niño episode of the century. Multiannual dengue cycles (2-5 y) were highly coherent with the Oceanic Niño Index, and synchrony of these cycles increased with temperature. We also detected localized traveling waves of multiannual dengue epidemic cycles in Thailand, Laos, and the Philippines that were dependent on temperature. This study reveals forcing mechanisms that drive synchronization of dengue epidemics on a continental scale across Southeast Asia.
  14. Slik JW, Arroyo-Rodríguez V, Aiba S, Alvarez-Loayza P, Alves LF, Ashton P, et al.
    Proc Natl Acad Sci U S A, 2015 Jun 16;112(24):7472-7.
    PMID: 26034279 DOI: 10.1073/pnas.1423147112
    The high species richness of tropical forests has long been recognized, yet there remains substantial uncertainty regarding the actual number of tropical tree species. Using a pantropical tree inventory database from closed canopy forests, consisting of 657,630 trees belonging to 11,371 species, we use a fitted value of Fisher's alpha and an approximate pantropical stem total to estimate the minimum number of tropical forest tree species to fall between ∼ 40,000 and ∼ 53,000, i.e., at the high end of previous estimates. Contrary to common assumption, the Indo-Pacific region was found to be as species-rich as the Neotropics, with both regions having a minimum of ∼ 19,000-25,000 tree species. Continental Africa is relatively depauperate with a minimum of ∼ 4,500-6,000 tree species. Very few species are shared among the African, American, and the Indo-Pacific regions. We provide a methodological framework for estimating species richness in trees that may help refine species richness estimates of tree-dependent taxa.
  15. Wilkinson JL, Boxall ABA, Kolpin DW, Leung KMY, Lai RWS, Galbán-Malagón C, et al.
    Proc Natl Acad Sci U S A, 2022 Feb 22;119(8).
    PMID: 35165193 DOI: 10.1073/pnas.2113947119
    Environmental exposure to active pharmaceutical ingredients (APIs) can have negative effects on the health of ecosystems and humans. While numerous studies have monitored APIs in rivers, these employ different analytical methods, measure different APIs, and have ignored many of the countries of the world. This makes it difficult to quantify the scale of the problem from a global perspective. Furthermore, comparison of the existing data, generated for different studies/regions/continents, is challenging due to the vast differences between the analytical methodologies employed. Here, we present a global-scale study of API pollution in 258 of the world's rivers, representing the environmental influence of 471.4 million people across 137 geographic regions. Samples were obtained from 1,052 locations in 104 countries (representing all continents and 36 countries not previously studied for API contamination) and analyzed for 61 APIs. Highest cumulative API concentrations were observed in sub-Saharan Africa, south Asia, and South America. The most contaminated sites were in low- to middle-income countries and were associated with areas with poor wastewater and waste management infrastructure and pharmaceutical manufacturing. The most frequently detected APIs were carbamazepine, metformin, and caffeine (a compound also arising from lifestyle use), which were detected at over half of the sites monitored. Concentrations of at least one API at 25.7% of the sampling sites were greater than concentrations considered safe for aquatic organisms, or which are of concern in terms of selection for antimicrobial resistance. Therefore, pharmaceutical pollution poses a global threat to environmental and human health, as well as to delivery of the United Nations Sustainable Development Goals.
  16. Yebra G, Harling-Lee JD, Lycett S, Aarestrup FM, Larsen G, Cavaco LM, et al.
    Proc Natl Acad Sci U S A, 2022 Dec 13;119(50):e2211217119.
    PMID: 36469788 DOI: 10.1073/pnas.2211217119
    Most new pathogens of humans and animals arise via switching events from distinct host species. However, our understanding of the evolutionary and ecological drivers of successful host adaptation, expansion, and dissemination are limited. Staphylococcus aureus is a major bacterial pathogen of humans and a leading cause of mastitis in dairy cows worldwide. Here we trace the evolutionary history of bovine S. aureus using a global dataset of 10,254 S. aureus genomes including 1,896 bovine isolates from 32 countries in 6 continents. We identified 7 major contemporary endemic clones of S. aureus causing bovine mastitis around the world and traced them back to 4 independent host-jump events from humans that occurred up to 2,500 y ago. Individual clones emerged and underwent clonal expansion from the mid-19th to late 20th century coinciding with the commercialization and industrialization of dairy farming, and older lineages have become globally distributed via established cattle trade links. Importantly, we identified lineage-dependent differences in the frequency of host transmission events between humans and cows in both directions revealing high risk clones threatening veterinary and human health. Finally, pangenome network analysis revealed that some bovine S. aureus lineages contained distinct sets of bovine-associated genes, consistent with multiple trajectories to host adaptation via gene acquisition. Taken together, we have dissected the evolutionary history of a major endemic pathogen of livestock providing a comprehensive temporal, geographic, and gene-level perspective of its remarkable success.
  17. Mills MB, Malhi Y, Ewers RM, Kho LK, Teh YA, Both S, et al.
    Proc Natl Acad Sci U S A, 2023 Jan 17;120(3):e2214462120.
    PMID: 36623189 DOI: 10.1073/pnas.2214462120
    Logged and structurally degraded tropical forests are fast becoming one of the most prevalent land-use types throughout the tropics and are routinely assumed to be a net carbon sink because they experience rapid rates of tree regrowth. Yet this assumption is based on forest biomass inventories that record carbon stock recovery but fail to account for the simultaneous losses of carbon from soil and necromass. Here, we used forest plots and an eddy covariance tower to quantify and partition net ecosystem CO2 exchange in Malaysian Borneo, a region that is a hot spot for deforestation and forest degradation. Our data represent the complete carbon budget for tropical forests measured throughout a logging event and subsequent recovery and found that they constitute a substantial and persistent net carbon source. Consistent with existing literature, our study showed a significantly greater woody biomass gain across moderately and heavily logged forests compared with unlogged forests, but this was counteracted by much larger carbon losses from soil organic matter and deadwood in logged forests. We estimate an average carbon source of 1.75 ± 0.94 Mg C ha-1 yr-1 within moderately logged plots and 5.23 ± 1.23 Mg C ha-1 yr-1 in unsustainably logged and severely degraded plots, with emissions continuing at these rates for at least one-decade post-logging. Our data directly contradict the default assumption that recovering logged and degraded tropical forests are net carbon sinks, implying the amount of carbon being sequestered across the world's tropical forests may be considerably lower than currently estimated.
  18. Lim CH, Soga T, Parhar IS
    Proc Natl Acad Sci U S A, 2023 Jan 17;120(3):e2117547120.
    PMID: 36623187 DOI: 10.1073/pnas.2117547120
    Social disturbance in interpersonal relationships is the primary source of stress in humans. Spexin (SPX, SPX1a in cichlid), an evolutionarily conserved neuropeptide with diverse physiological functions, is up-regulated in the brain during chronic social defeat stress in teleost. On the other hand, repeated exposure to social stress can lead to dysregulation of the monoaminergic system and increase the vulnerability of developing depression. Since dysfunction of the serotonin (5-hydroxytryptamine, 5-HT) system is associated with social stress and the pathophysiology of depression, the present study investigated the regulatory relationship between the central 5-HT system and SPX1a in the male teleost, Nile tilapia (Oreochromis niloticus). To identify stress factors that regulate SPX1a gene expression, cortisol, dexamethasone (DEX), and 5-HT were used to treat tilapia brain primary cultures. Our study shows cortisol and DEX treatment had no effect on SPX1a gene expression, but SPX1a gene expression was down-regulated following 5-HT treatment. Anatomical localization showed a close association between 5-HT immunoreactive projections and SPX1a neurons in the semicircular torus. In addition, 5-HT receptors (5-HT2B) were expressed in SPX1a neurons. SPX1a immunoreactive neurons and SPX1a gene expression were significantly increased in socially defeated tilapia. On the other hand, citalopram (antidepressant, 5-HT antagonist) treatment to socially defeated tilapia normalized SPX1a gene expression to control levels. Taken together, the present study shows that 5-HT is an upstream regulator of SPX1a and that the inhibited 5-HT activates SPX1a during social defeat.
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