Search

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 10th 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.

Abstract Background 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. Results 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. Conclusions 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.

Abstract The neural functions of adropin, a secreted peptide highly expressed in the brain, have not been investigated. In humans, adropin is highly expressed in astrocytes and peaks during critical postnatal periods of brain development. Gene enrichment analysis of transcripts correlating with adropin expression suggests processes relevant to aging-related neurodegenerative diseases that vary with age and dementia state, possibly indicating survivor bias. In people aged 75 y) diagnosed with dementia, adropin correlates positively with genes involved in mitochondrial processes. In the ‘old-old’ without dementia adropin expression correlates positively with morphogenesis and synapse function. Potent neurotrophic responses in primary cultured neurons are consistent with adropin supporting the development and function of neural networks. Adropin expression in the ‘old-old’ also correlates positively with protein markers of tau-related neuropathologies and inflammation, particularly in those without dementia. How variation in brain adropin expression affects neurological aging was investigated using old (18-month) C57BL/6J mice. In mice adropin is expressed in neurons, oligodendrocyte progenitor cells, oligodendrocytes, and microglia and shows correlative relationships with groups of genes involved in neurodegeneration and cellular metabolism. Increasing adropin expression using transgenesis improved spatial learning and memory, novel object recognition, resilience to exposure to new environments, and reduced mRNA markers of inflammation in old mice. Treatment with synthetic adropin peptide also reversed age-related declines in cognitive functions and affected expression of genes involved in morphogenesis and cellular metabolism. Collectively, these results establish a link between adropin expression and neural energy metabolism and indicate a potential therapy against neurological aging.

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.

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.

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.

A recurrent de novo mutation in the transcriptional corepressor CTBP1 is associated with neurodevelopmental disabilities in children (Beck et al., 2016, 2019; Sommerville et al., 2017). All reported patients harbor a single recurrent de novo heterozygous missense mutation (p.R342W) within the cofactor recruitment domain of CtBP1. To investigate the transcriptional activity of the pathogenic CTBP1 mutant allele in physiologically relevant human cell models, we generated induced pluripotent stem cells (iPSC) from the dermal fibroblasts derived from patients and normal donors. The transcriptional profiles of the iPSC-derived “early” neurons were determined by RNA-sequencing. Comparison of the RNA-seq data of the neurons from patients and normal donors revealed down regulation of gene networks involved in neurodevelopment, synaptic adhesion and anti-viral (interferon) response. Consistent with the altered gene expression patterns, the patient-derived neurons exhibited morphological and electrophysiological abnormalities, and susceptibility to viral infection. Taken together, our studies using iPSC-derived neuron models provide novel insights into the pathological activities of the CTBP1 p.R342W allele.

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.

Connections between neurons called synapses are the key components underlying all nervous system functions of animals and humans. However, important genetic information on the formation and plasticity of one type, the electrical (gap junction-mediated) synapse, is understudied in many invertebrates. In the present study, we set forth to identify and characterize the gap junction-encoding gene innexin in the central nervous system (CNS) of the mollusk pond snail Lymnaea stagnalis. With PCR, 3′ and 5′ RACE, and BLAST searches, we identified eight innexin genes in the L. stagnalis genome, named Lst Inx1–Lst Inx8. Phylogenetic analysis revealed that the L. stagnalis innexin genes originated from a single copy in the common ancestor of molluskan species by multiple gene duplication events and have been maintained in L. stagnalis since they were generated. The paralogous innexin genes demonstrate distinct expression patterns among tissues. In addition, one paralog, Lst Inx1, exhibits heterogeneity in cells and ganglia, suggesting the occurrence of functional diversification after gene duplication. These results introduce possibilities to study an intriguing potential relationship between innexin paralog expression and cell-specific functional outputs such as heterogenic ability to form channels and exhibit synapse plasticity. The L. stagnalis CNS contains large neurons and functionally defined networks for behaviors; with the introduction of L. stagnalis in the gap junction gene field, we are providing novel opportunities to combine genetic research with direct investigations of functional outcomes at the cellular, synaptic, and behavioral levels.

Abstract Background 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. Methods 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. Setting: NSW Australia. Subjects: all women who gave birth to their first child in NSW between 1 January 2004 and 31 December 2008. Results 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). Conclusions 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.

Abstract In the central nervous system (CNS), cholinergic transmission induces synaptic plasticity that is required for learning and memory. However, our understanding of the development and maintenance of cholinergic circuits is limited, as the factors regulating the expression and clustering of neuronal nicotinic acetylcholine receptors (nAChRs) remain poorly defined. Recent studies from our group have implicated calpain-dependent proteolytic fragments of menin, the product of the MEN1 tumor suppressor gene, in coordinating the transcription and synaptic clustering of nAChRs in invertebrate central neurons. Here, we sought to determine whether an analogous cholinergic mechanism underlies menin’s synaptogenic function in the vertebrate CNS. Our data from mouse primary hippocampal cultures demonstrate that menin and its calpain-dependent C-terminal fragment (C-menin) regulate the subunit-specific transcription and synaptic clustering of neuronal nAChRs, respectively. MEN1 knockdown decreased nAChR α5 subunit expression, the clustering of α7 subunit-containing nAChRs at glutamatergic presynaptic terminals, and nicotine-induced presynaptic facilitation. Moreover, the number and function of glutamatergic synapses was unaffected by MEN1 knockdown, indicating that the synaptogenic actions of menin are specific to cholinergic regulation. Taken together, our results suggest that the influence of menin on synapse formation and synaptic plasticity occur via modulation of nAChR channel subunit composition and functional clustering.

Background: Hepatitis C virus (HCV) is common among people who inject drugs (PWID) on methadone program in Iran (Persia). However, a few PWID on methadone program report willingness to receive HCV treatment. This study aimed to assess the factors which were associated with willingness to receive HCV treatment in a group of PWID on methadone program in Iran.Methods: We surveyed 187 PWID at seven drops in centers in Tehran, Iran. Details of demographic characteristics, drug use, injection, HCV, and drug treatment history were collected a using 25-item questionnaire. Participants were serologically tested for the current status of HCV.Findings: The study found that 28.3% of the participants were HCV seropositive. In total, 49.1% of the participants reported unwillingness to receive HCV treatment. Awareness of current HCV status [odds ratio (OR) = 3.43; 95% confidence interval (CI): 1.33-7.26; P < 0.050]; adequate knowledge of HCV treatment centers in the community (OR = 3.9; 95% CI: 1.24-5.38; P < 0.050); participation in an educational program on HCV (OR = 2.9; 95% CI: 2.33-8.56; P < 0.001) and recent participation in the meetings of self-help groups (OR = 4.6; 95% CI: 3.43-9.33; P < 0.001) were significantly associated with current willingness to receive HCV treatment. Conclusion:The study results indicate that awareness of HCV status and the provision of adequate HCV education via different information centers can be associated with an increased willingness for HCV treatment among PWID on methadone program. Conducting more research is suggested to assess the efficacy of educational programs and self-help groups in facilitating HCV treatment among PWID on methadone program.

Background Mental disorders of women during the postnatal period are a major public health problem. Compared with women's mental disorders, much less attention has been paid to men's mental disorders in the perinatal period. To date, there have been no reports in the literature describing secular changes of both maternal and paternal hospital admissions for mental disorders over the period covering the year before pregnancy (non-parents), during pregnancy (expectant parents) and up to the first year after birth (parents) based on linked parental data. The co-occurrences of couples' hospital admissions for mental disorders have not previously been investigated. Aims To describe maternal and paternal hospital admissions for mental disorders before and after birth. To compare the co-occurrences of parents' hospital admissions for mental disorder in the perinatal period. Method This is a cohort study using paired parents' population data from the New South Wales (NSW) Perinatal Data Collection (PDC), Registry of Births, Deaths and Marriages (RBDM) and Admitted Patients Data Collection (APDC). The study included all parents (n=196 669 couples) who gave birth to their first child in NSW between 1 January 2003 and 31 December 2009. Results The hospital admission rate for women with a principal mental disorder diagnosis in the period between the year before pregnancy and the first year after birth was significantly higher than that for men. Parents' mental disorders influenced each other. If a man was admitted to hospital with a principal mental disorder diagnosis, his wife or partner was more likely to be admitted to hospital with a principal mental disorder diagnosis compared with women whose partner had not had a hospital admission, and vice versa. Conclusions Mothers' mental disorders after birth increased more significantly than fathers. However, fathers' mental disorders significantly impacted the co-occurrence of mothers' mental disorders.

Octopus vulgaris is a unique model system for studying complex behaviors in animals. It has a large and centralized nervous system made up of lobes that are involved in controlling various sophisticated behaviors. As such, it may be considered as a model organism for untangling the neuronal mechanisms underlying behaviors—including learning and memory. However, despite considerable efforts, Octopus lags behind its other counterparts vis-à-vis its utility in deciphering the cellular, molecular and synaptic mechanisms underlying various behaviors. This study represents a novel approach designed to establish a neuronal cell culture protocol that makes this species amenable to further exploitation as a model system. Here we developed a protocol that enables dissociation of neurons from two specific Octopus' brain regions, the vertical-superior frontal system and the optic lobes, which are involved in memory, learning, sensory integration and adult neurogenesis. In particular, cells dissociated with enzyme papain and cultured on Poly-D-Lysine-coated dishes with L15-medium and fetal bovine serum yielded high neuronal survival, axon growth, and re-growth after injury. This model was also explored to define optimal culture conditions and to demonstrate the regenerative capabilities of adult Octopus neurons after axotomy. This study thus further underscores the importance of Octopus neurons as a model system for deciphering fundamental molecular and cellular mechanism of complex brain function and underlying behaviors.

Accumulated soluble amyloid beta- (Aβ-) induced aberrant neuronal network activity may directly contribute to cognitive deficits, which are the most outstanding characteristics of Alzheimer’s disease (AD). The entorhinal cortex (EC) is one of the earliest affected brain regions in AD. Impairments of EC neurons are responsible for the cognitive deficits in AD. However, little effort has been made to investigate the effects of soluble Aβ on the discharge properties of EC neurons in vivo. The present study was designed to examine the effects of soluble Aβ1−42 on the discharge properties of EC neurons, using in vivo extracellular single unit recordings. The protective effects of gastrodin (GAS) were also investigated against Aβ1−42-induced alterations in EC neuronal activities. The results showed that the spontaneous discharge of EC neurons was increased by local application of soluble Aβ1−42 and that GAS can effectively reverse Aβ1−42-induced facilitation of spontaneous discharge in a concentration-dependent manner. Moreover, whole-cell patch clamp results indicated that the protective function of GAS on abnormal hyperexcitability may be partially mediated by its inhibitory action on Aβ1−42-elicited inward currents in EC neurons. Our study suggested that GAS may provide neuroprotective effects on Aβ1−42-induced hyperactivity in EC neurons of rats.

Cysteine string protein (CSPalpha) is a synaptic vesicle protein that displays unique anti-neurodegenerative properties. CSPalpha is a member of the conserved J protein family, also called the Hsp40 (heat shock protein of 40 kDa) protein family, whose importance in protein folding has been recognized for many years. Deletion of the CSPalpha in mice results in knockout mice that are normal for the first 2-3 weeks of life followed by an unexplained presynaptic neurodegeneration and premature death. How CSPalpha prevents neurodegeneration is currently not known. As a neuroprotective synaptic vesicle protein, CSPalpha represents a promising therapeutic target for the prevention of neurodegenerative disorders.Here, we demonstrate that the flavonoid quercetin promotes formation of stable CSPalpha-CSPalpha dimers and that quercetin-induced dimerization is dependent on the unique cysteine string region. Furthermore, in primary cultures of Lymnaea neurons, quercetin induction of CSPalpha dimers correlates with an inhibition of synapse formation and synaptic transmission suggesting that quercetin interfers with CSPalpha function. Quercetin's action on CSPalpha is concentration dependent and does not promote dimerization of other synaptic proteins or other J protein family members and reduces the assembly of CSPalpha:Hsc70 units (70kDa heat shock cognate protein).Quercetin is a plant derived flavonoid and popular nutritional supplement proposed to prevent memory loss and altitude sickness among other ailments, although its precise mechanism(s) of action has been unclear. In view of the therapeutic promise of upregulation of CSPalpha and the undesired consequences of CSPalpha dysfunction, our data establish an essential proof of principle that pharmaceutical agents can selectively target the neuroprotective J protein CSPalpha.

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 3b (GSK3b), kinases implicated in autophagy function, increased with PGRN treatment under stress. Together, our data suggest that PGRN prevents hyperglycemiainduced decreases in autophagy by increasing autophagy flux via increased ERK1/2 kinase activity in primary rat cortical neurons. [ABSTRACT FROM AUTHOR]