The pond snail, Lymnaea stagnalis (L. stagnalis), has served as a valuable model organism for neurobiology studies due to its simple and easily accessible central nervous system (CNS). L. stagnalis ...has been widely used to study neuronal networks and recently gained popularity for study of aging and neurodegenerative diseases. However, previous transcriptome studies of L. stagnalis CNS have been exclusively carried out on adult L. stagnalis only. As part of our ongoing effort studying L. stagnalis neuronal growth and connectivity at various developmental stages, we provide the first age-specific transcriptome analysis and gene annotation of young (3 months), adult (6 months), and old (18 months) L. stagnalis CNS. Using the above three age cohorts, our study generated 55-69 millions of 150 bp paired-end RNA sequencing reads using the Illumina NovaSeq 6000 platform. Of these reads, ~ 74% were successfully mapped to the reference genome of L. stagnalis. Our reference-based transcriptome assembly predicted 42,478 gene loci, of which 37,661 genes encode coding sequences (CDS) of at least 100 codons. In addition, we provide gene annotations using Blast2GO and functional annotations using Pfam for ~ 95% of these sequences, contributing to the largest number of annotated genes in L. stagnalis CNS so far. Moreover, among 242 previously cloned L. stagnalis genes, we were able to match ~ 87% of them in our transcriptome assembly, indicating a high percentage of gene coverage. The expressional differences for innexins, FMRFamide, and molluscan insulin peptide genes were validated by real-time qPCR. Lastly, our transcriptomic analyses revealed distinct, age-specific gene clusters, differentially expressed genes, and enriched pathways in young, adult, and old CNS. More specifically, our data show significant changes in expression of critical genes involved in transcription factors, metabolisms (e.g. cytochrome P450), extracellular matrix constituent, and signaling receptor and transduction (e.g. receptors for acetylcholine, N-Methyl-D-aspartic acid, and serotonin), as well as stress- and disease-related genes in young compared to either adult or old snails. Together, these datasets are the largest and most updated L. stagnalis CNS transcriptomes, which will serve as a resource for future molecular studies and functional annotation of transcripts and genes in L. stagnalis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
International research shows marital status impacts the mental health of pregnant women, with prenatal depression and anxiety being higher among non-partnered women. However, ...there have been few studies examining the relationship between marital status and prenatal mental disorders among Australian women.
Methods
This is a population-based retrospective cohort study using linked data from the New South Wales (NSW) Perinatal Data Collection (PDC) and Admitted Patients Data Collection (APDC). The cohort consists of a total of 598,599 pregnant women with 865,349 admissions. Identification of pregnant women for mental disorders was conducted using the 10
th
version International Classification of Diseases and Related Health Problems, Australian Modification (ICD-10-AM). A binary logistic regression model was used to estimate the relationship between marital status and prenatal mental disorder after adjusting for confounders.
Results
Of the included pregnant women, 241 (0.04%), 107 (0.02%) and 4359 (0.5%) were diagnosed with depressive disorder, anxiety disorder, and self-harm, respectively. Non-partnered pregnant women had a higher likelihood of depressive disorder (Adjusted Odds Ratio (AOR) = 2.75; 95% CI: 2.04, 3.70) and anxiety disorder (AOR = 3.16, 95% CI: 2.03, 4.91), compared with partnered women. Furthermore, the likelihood of experiencing self-harm was two times higher among non-partnered pregnant women (AOR = 2.00; 95% CI: 1.82, 2.20) than partnered pregnant women.
Conclusions
Non-partnered marital status has a significant positive association with prenatal depressive disorder, anxiety disorder and self-harm. This suggests it would be highly beneficial for maternal health care professionals to screen non-partnered pregnant women for prenatal mental health problems such as depression, anxiety and self-harm.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Silver nanoparticles (AgNPs), owing to their effective antimicrobial properties, are being widely used in a broad range of applications. These include, but are not limited to, antibacterial ...materials, the textile industry, cosmetics, coatings of various household appliances and medical devices. Despite their extensive use, little is known about AgNP safety and toxicity vis-à-vis human and animal health. Recent studies have drawn attention towards potential neurotoxic effects of AgNPs, however, the primary cellular and molecular targets of AgNP action/s remain to be defined.
Here we examine the effects of ultra fine scales (20 nm) of AgNPs at various concentrations (1, 5, 10 and 50 μg/ml) on primary rat cortical cell cultures. We found that AgNPs (at 1-50 μg/ml) not only inhibited neurite outgrowth and reduced cell viability of premature neurons and glial cells, but also induced degeneration of neuronal processes of mature neurons. Our immunocytochemistry and confocal microscopy studies further demonstrated that AgNPs induced the loss of cytoskeleton components such as the β-tubulin and filamentous actin (F-actin). AgNPs also dramatically reduced the number of synaptic clusters of the presynaptic vesicle protein synaptophysin, and the postsynaptic receptor density protein PSD-95. Finally, AgNP exposure also resulted in mitochondria dysfunction in rat cortical cells.
Taken together, our data show that AgNPs induce toxicity in neurons, which involves degradation of cytoskeleton components, perturbations of pre- and postsynaptic proteins, and mitochondrial dysfunction leading to cell death. Our study clearly demonstrates the potential detrimental effects of AgNPs on neuronal development and physiological functions and warns against its prolific usage.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Anaerobic digestion (AD) is a triple-benefit biotechnology for organic waste treatment, renewable production, and carbon emission reduction. In the process of anaerobic digestion, pH, temperature, ...organic load, ammonia nitrogen, VFAs, and other factors affect fermentation efficiency and stability. The balance between the generation and consumption of volatile fatty acids (VFAs) in the anaerobic digestion process is the key to stable AD operation. However, the accumulation of VFAs frequently occurs, especially propionate, because its oxidation has the highest Gibbs free energy when compared to other VFAs. In order to solve this problem, some strategies, including buffering addition, suspension of feeding, decreased organic loading rate, and so on, have been proposed. Emerging methods, such as bioaugmentation, supplementary trace elements, the addition of electronic receptors, conductive materials, and the degasification of dissolved hydrogen, have been recently researched, presenting promising results. But the efficacy of these methods still requires further studies and tests regarding full-scale application. The main objective of this paper is to provide a comprehensive review of the mechanisms of propionate generation, the metabolic pathways and the influencing factors during the AD process, and the recent literature regarding the experimental research related to the efficacy of various strategies for enhancing propionate biodegradation. In addition, the issues that must be addressed in the future and the focus of future research are identified, and the potential directions for future development are predicted.
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Type II diabetes affects over 530 million individuals worldwide and contributes to a host of neurological pathologies. Uncontrolled high blood glucose (hyperglycemia) is a major factor in diabetic ...pathology, and glucose regulation is a common goal for maintenance in patients. We have found that the neuronal growth factor progranulin protects against hyperglycemic stress in neurons, and although its mechanism of action is uncertain, our findings identified Glycogen Synthase Kinase 3β (GSK3β) as being potentially involved in its effects. In this study, we treated mouse primary cortical neurons exposed to high-glucose conditions with progranulin and a selective pharmacological inhibitor of GSK3β before assessing neuronal health and function. Whole-cell and mitochondrial viability were both improved by progranulin under high-glucose stress in a GSK3β-dependent manner. This extended to autophagy flux, indicated by the expressions of autophagosome marker Light Chain 3B (LC3B) and lysosome marker Lysosome-Associated Membrane Protein 2A (LAMP2A), which were affected by progranulin and showed heterogeneous changes from GSK3β inhibition. Lastly, GSK3β inhibition attenuated downstream calcium signaling and neuronal firing effects due to acute progranulin treatment. These data indicate that GSK3β plays an important role in progranulin's neuroprotective effects under hyperglycemic stress and serves as a jumping-off point to explore progranulin's protective capabilities in other neurodegenerative models.
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Chronic hyperglycemia in type II diabetes results in impaired autophagy function, accumulation of protein aggregates, and neurodegeneration. However, little is known about how to preserve autophagy ...function under hyperglycemic conditions. In this study, we tested whether progranulin (PGRN), a neurotrophic factor required for proper lysosome function, can restore autophagy function in neurons under high-glucose stress. We cultured primary cortical neurons derived from E18 Sprague-Dawley rat pups to maturity at 10 days
in vitro
(DIV) before incubation in high glucose medium and PGRN for 24-72 h before testing for autophagy flux, protein turnover, and mitochondrial function. We found that although PGRN by itself did not upregulate autophagy, it attenuated impairments in autophagy seen under high-glucose conditions. Additionally, buildup of the autophagosome marker light chain 3B (LC3B) and lysosome marker lysosome-associated membrane protein 2A (LAMP2A) changed in both neurons and astrocytes, indicating a possible role for glia in autophagy flux. Protein turnover, assessed by remaining advanced glycation end-product levels after a 6-h incubation, was preserved with PGRN treatment. Mitochondrial activity differed by complex, although PGRN appeared to increase overall activity in high glucose. We also found that activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and glycogen synthase kinase 3β (GSK3β), kinases implicated in autophagy function, increased with PGRN treatment under stress. Together, our data suggest that PGRN prevents hyperglycemia-induced decreases in autophagy by increasing autophagy flux via increased ERK1/2 kinase activity in primary rat cortical neurons.
Taurine is a sulfur-containing amino acid that is widely expressed throughout the human brain, heart, retina, and muscle tissues. Taurine deficiency is associated with cardiomyopathy, renal ...dysfunction, abnormalities of the developing nervous system, and epilepsy which suggests a role specific to excitable tissues. Like vertebrates, invertebrates maintain high levels of taurine during embryonic and larval development, which decline during aging, indicating a potential developmental role. Notwithstanding its extensive presence throughout, taurine’s precise role/s during early brain development, function, and repair remains largely unknown in both vertebrate and invertebrate. Here, we investigated whether taurine affects neurite outgrowth, synapse formation, and synaptic transmission between postnatal day 0 rat cortical neurons
in vitro
, whereas its synaptogenic role was tested more directly using the
Lymnaea
soma-soma synapse model. We provide direct evidence that when applied at physiological concentrations, taurine exerts a significant neurotrophic effect on neuritic outgrowth and thickness of neurites as well as the expression of synaptic puncta as revealed by immunostaining of presynaptic synaptophysin and postsynaptic PSD95 proteins in rat cortical neurons, indicating direct involvement in synapse development. To demonstrate taurine’s direct effects on neurons in the absence of glia and other confounding factors, we next exploited individually identified pre- and postsynaptic neurons from the mollusk
Lymnaea stagnalis
. We found that taurine increased both the incidence of synapse formation (percent of cells that form synapses) and the efficacy of synaptic transmission between the paired neurons. This effect was comparable, but not additive, to
Lymnaea
trophic factor-induced synaptogenesis. This study thus provides direct morphological and functional evidence that taurine plays an important role in neurite outgrowth, synaptogenesis, and synaptic transmission during the early stages of brain development and that this role is conserved across both vertebrate and invertebrate species.
Mercury is a well-known neurotoxin implicated in a wide range of neurological or psychiatric disorders including autism spectrum disorders, Alzheimer's disease, Parkinson's disease, epilepsy, ...depression, mood disorders and tremor. Mercury-induced neuronal degeneration is thought to invoke glutamate-mediated excitotoxicity, however, the underlying mechanisms remain poorly understood. Here, we examine the effects of various mercury concentrations (including pathological levels present in human plasma or cerebrospinal fluid) on cultured, rat cortical neurons.
We found that inorganic mercuric chloride (HgCl₂--at 0.025 to 25 μM) not only caused neuronal degeneration but also perturbed neuronal excitability. Whole-cell patch-clamp recordings of pyramidal neurons revealed that HgCl₂ not only enhanced the amplitude and frequency of synaptic, inward currents, but also increased spontaneous synaptic potentials followed by sustained membrane depolarization. HgCl₂ also triggered sustained, 2-5 fold rises in intracellular calcium concentration (Ca²⁺i). The observed increases in neuronal activity and Ca²⁺i were substantially reduced by the application of MK 801, a non-competitive antagonist of N-Methyl-D-Aspartate (NMDA) receptors. Importantly, our study further shows that a pre incubation or co-application of MK 801 prevents HgCl₂-induced reduction of cell viability and a disruption of β-tubulin.
Collectively, our data show that HgCl₂-induced toxic effects on central neurons are triggered by an over-activation of NMDA receptors, leading to cytoskeleton instability.
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Purpose
The early postnatal period is a time of increased risk for psychiatric admission. However, there is scope to further examine if this increase in risk extends to the entire perinatal period ...(pregnancy and first postnatal year), and how it compares to admission outside of the perinatal period.
Methods
Data were linked across birth and hospital admission registers from July 2000 to December 2009. The study cohort, consisting of all pregnant and childbearing women with a psychiatric history, was divided into two groups: case women (at least one perinatal principal psychiatric admission in the study period) (38%) and comparison women (no perinatal principal psychiatric admissions) (62%). Outcomes were admission rate and length of stay adjusted for diagnosis, socio-demographic factors and timing of admission.
Results
Antenatal and postnatal admissions rates were both higher than non-perinatal admission rates for
case
women for all diagnoses. There was little evidence that women with perinatal admissions were at an increased risk of admissions at other times. Socially disadvantaged women had significantly fewer and shorter admissions than their respective counterparts.
Conclusions
The entire perinatal period is a time of increased risk for admission across the range of psychiatric disorders, compared to other times in a woman’s childbearing years. Reduced admission rate and length of stay for socially disadvantaged women suggest lack of equity of access highlighting the importance of national perinatal mental health policy initiatives inclusive of disadvantaged groups.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To investigate the rates of hospitalisation for anaemia and depression in women in the six-year period (3 years before and after birth). To compare hospital admissions for depression in women with ...and without anaemia.
This is a population-based cohort study. Women's birth records (New South Wales (NSW) Perinatal Data Collection) were linked with NSW Admitted Patients Data Collection records between 1 January 2001 and 31 December 2010, so that hospital admissions for mothers could be traced back for 3 years before birth and followed up 3 years after birth.
NSW Australia.
all women who gave birth to their first child in NSW between 1 January 2004 and 31 December 2008.
Hospital admissions for both anaemia and depression were increased significantly in the year just before and after birth compared with the years before and after. Women with anaemia were more likely to be admitted to hospital for depression than those without (for principal diagnosis of depression, adjusted OR = 1.62, 95% CI = 1.25-2.11; for all diagnosis of depression, adjusted OR = 2.01, 95% CI = 1.70-2.38).
Depression was associated with anaemia in women before and after birth. This finding highlight the important role of primary care providers in assessing for both anaemia and depressive symptomatology together, given the relationship between the two. Treating or preventing anaemia may help to prevent postnatal depression.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK