Neural Cells Research Articles

Piezoelectric Analgesia Blocks Cancer-Induced Bone Pain.

The manipulation of cell surface receptors' activity will open a new frontier for drug development and disease treatment. However, limited by the desensitization of drugs, effective physical intervention strategy remains challenging. Here, the controllable internalization of transient receptor potential vanilloid 1 (TRPV1) on neural cells by local piezoelectric field is reported. Single-cell-level local electric field is construct by synthesizing piezoelectric BiOIO3 nanosheets (BIONSs). Upon a mild ultrasound of 0.08Wcm-2, an electric field of 15.29µV is generated on the surface of BIONSs, further inducing TRPV1 internalization in 5min. The as-downregulated TRPV1 expression results in the reduction of Ca2+ signal in a spinal neuron and the inhibition of the activity of wide range dynamic neurons, therefore effectively preventing the transmission of cancer-induced bone pain (CIBP). This strategy not only charts a new course for CIBP alleviation, but also introduces a promising nanotechnology for regulating cell surface receptors, showing significant potential in neuropathological and receptor-related diseases.

Methadone directly impairs central nervous system cells in vitro

Methadone is a synthetic long-acting opioid that is increasingly used in the replacement therapy of opioid-addicted patients, including pregnant women. However, methadone therapy in this population poses challenges, as it induces cognitive and behavioral impairments in infants exposed to this opioid during prenatal development. In animal models, prenatal methadone exposure results in detrimental consequences to the central nervous system, such as: (i) increased neuronal apoptosis; (ii) disruption of oligodendrocyte maturation and increased apoptosis and (iii) increased microglia and astrocyte activation. However, it remains unclear whether these deleterious effects result from a direct effect of methadone on brain cells. Therefore, our goal was to uncover the impact of methadone on single brain cell types in vitro. Primary cultures of rat neurons, oligodendrocytes, microglia, and astrocytes were treated for three days with 10 µM methadone to emulate a chronic administration. Apoptotic neurons were identified by cleaved caspase-3 detection, and synaptic density was assessed by the juxtaposition of presynaptic and postsynaptic markers. Apoptosis of oligodendrocyte precursors was determined by cleaved caspase-3 detection. Oligodendrocyte myelination was assessed by immunofluorescence, while microglia and astrocyte proinflammatory activation were assessed by both immunofluorescence and RT-qPCR. Methadone treatment increased neuronal apoptosis and reduced synaptic density. Furthermore, it led to increased oligodendrocyte apoptosis and a reduction in the myelinating capacity of these cells, and promoted the proinflammatory activation of microglia and astrocytes. We showed that methadone, the most widely used drug in opioid replacement therapy for pregnant women with opioid addiction, directly impairs brain cells in vitro, highlighting the need for developing alternative therapies to address opioid addiction in this population.

A Comprehensive Protocol for Efficient Differentiation of Human NPCs into Electrically Competent Neurons

BackgroundThe study of neurons is fundamental to unraveling the complexities of the nervous system. Primary neuronal cultures from rodents have long been a cornerstone of experimental studies, yet limitations related to their non-human nature and ethical concerns have prompted the development of alternatives. In recent years, the derivation of neurons from human-induced pluripotent stem cells (hiPSCs) has emerged as a powerful option, offering a scalable source of cells for diverse applications. Neural progenitor cells (NPCs) derived from hiPSCs can be efficiently differentiated into functional neurons, providing a platform to study human neural physiology and pathology in vitro. However, challenges persist in achieving consistent and reproducible outcomes across experimental settings. Comparison with existing methodsOur aim is to provide a step-by-step methodological protocol, augmenting existing procedures with additional instructions and parameters, to guide researchers in achieving reproducible results. Methods and resultsWe outline procedures for the differentiation of hiPSC-derived NPCs into electrically competent neurons, encompassing initial cell density, morphology, maintenance, and differentiation. We also describe the analysis of specific markers for assessing neuronal phenotype, along with electrophysiological analysis to evaluate biophysical properties of neuronal excitability. Additionally, we conduct a comparative analysis of three different chemical methods—KCl, N-methyl-D-aspartate (NMDA), and bicuculline—to induce neuronal depolarization and assess their effects on the induction of both fast and slow post-translational, transcriptional, and post-transcriptional responses. ConclusionOur protocol provides clear instructions for generating reliable human neuronal cultures with defined electrophysiological properties to investigate neuronal differentiation and model diseases in vitro.

MiR-203 secreted in extracellular vesicles mediates the communication between neural crest and placode cells required for trigeminal ganglia formation.

While interactions between neural crest and placode cells are critical for the proper formation of the trigeminal ganglion, the mechanisms underlying this process remain largely uncharacterized. Here, by using chick embryos, we show that the microRNA (miR)-203, whose epigenetic repression is required for neural crest migration, is reactivated in coalescing and condensing trigeminal ganglion cells. Overexpression of miR-203 induces ectopic coalescence of neural crest cells and increases ganglion size. By employing cell-specific electroporations for either miR-203 sponging or genomic editing using CRISPR/Cas9, we elucidated that neural crest cells serve as the source, while placode cells serve as the site of action for miR-203 in trigeminal ganglion condensation. Demonstrating intercellular communication, overexpression of miR-203 in the neural crest in vitro or in vivo represses an miR-responsive sensor in placode cells. Moreover, neural crest-secreted extracellular vesicles (EVs), visualized using pHluorin-CD63 vector, become incorporated into the cytoplasm of placode cells. Finally, RT-PCR analysis shows that small EVs isolated from condensing trigeminal ganglia are selectively loaded with miR-203. Together, our findings reveal a critical role in vivo for neural crest-placode communication mediated by sEVs and their selective microRNA cargo for proper trigeminal ganglion formation.

Gestational physical activity alters offspring brain APP processing in an age-specific manner.

Maternal exercise is beneficial for offspring brain development. Amyloid precursor protein (APP) influences neurogenesis and synaptic plasticity. Cleavage products of APP are implicated in the proliferation of neural progenitor cells and neuronal network development. Our study aimed to investigate differences in APP processing in active or sedentary offspring of dams who were exposed to voluntary wheel running with and without a western diet throughout gestation. Female Wistar rats (7-8 weeks old) were fed a normal chow or western diet and randomized into voluntary wheel run or sedentary conditions. Dams returned to sedentary conditions post-parturition. The pups were weaned at 6 weeks after which point half of the samples were collected, while the rest of the pups remained on a normal diet, separated into sedentary or voluntary wheel run groups, and collected 12 weeks later. In-utero exposure to maternal exercise was associated with higher neuronal nuclear protein, higher soluble APPα and lower soluble APPβ in offspring prefrontal cortex tissue at 6, but not 18 weeks of age. Neuronal nuclear protein is exclusive to mature neurons implying that offspring of mothers who exercised could have more neuron maturation potentially influenced by the higher APPα content at this early developmental stage. The voluntary wheel run offspring groups had a higher mature/pro brain derived neurotrophic factor ratio compared to the sedentary counterparts. The maternal effects were isolated to the juvenile 6-week-old pups, while the differences in the adult offspring were caused by their own exercise status.

Exploring the association between haematological markers of iron and general movements in 4-month-old infants exposed to anaemia in-utero

BackgroundIron is a vital micronutrient for brain development, influencing myelination, neurotransmitter balance, and the maturation of specific brain cells. Hence iron insufficiency in the foetal, neonatal and infancy period has the potential to influence the neuromotor development. AimsWe aimed to describe haematological markers of iron at 4 months of age in infants exposed to prenatal anaemia and explore the association with their quality of general movements. Study designCross sectional study nested within the RAPIDIRON-KIDS trial. SubjectsAll infants whose mothers were part of RAPIDIRON-KIDS trial, were eligible to participate in this study when the infants were 4 months old. Children suffering from fever or acute illness on the day of assessment, or with a history of either surgery, or admission to hospital in the first month were excluded. Outcome measuresHaematological markers of iron (Haemoglobin and Ferritin level) and quality of general movements in infants at 4 months of age. Results120 infants were assessed with mean birth weight of 2685.5 g (±384.5) and median gestational age of 39 weeks [Q1, Q3:38,40]. There was no significant association between haemoglobin or ferritin levels with fidgety movements (p = 0.18 and p = 0.27, respectively). The combined effect of haemoglobin and ferritin estimates also did not show any significant association with the study groups (p = 0.21). ConclusionA majority of infants still had low iron indices at 4 months of age and this was not associated with the quality of general movements. A prospective longitudinal study needs to be considered in infants exposed to prenatal anaemia rather than assessing the outcomes at a single time point.

Molecular overlaps of neurological manifestations of COVID-19 and schizophrenia from a proteomic perspective.

COVID-19, a complex multisystem disorder affecting the central nervous system, can also have psychiatric sequelae. In addition, clinical evidence indicates that a diagnosis of a schizophrenia spectrum disorder is a risk factor for mortality in patients with COVID-19. In this study, we aimed to explore brain-specific molecular aspects of COVID-19 by using a proteomic approach. We analyzed the brain proteome of fatal COVID-19 cases and compared it with differentially regulated proteins found in postmortem schizophrenia brains. The COVID-19 proteomic dataset revealed a strong enrichment of proteins expressed by glial and neuronal cells and processes related to diseases with a psychiatric and neurodegenerative component. Specifically, the COVID-19 brain proteome enriches processes that are hallmark features of schizophrenia. Furthermore, we identified shared and distinct molecular pathways affected in both conditions. We found that brain ageing processes are likely present in both COVID-19 and schizophrenia, albeit possibly driven by distinct processes. In addition, alterations in brain cell metabolism were observed, with schizophrenia primarily impacting amino acid metabolism and COVID-19 predominantly affecting carbohydrate metabolism. The enrichment of metabolic pathways associated with astrocytic components in both conditions suggests the involvement of this cell type in the pathogenesis. Both COVID-19 and schizophrenia influenced neurotransmitter systems, but with distinct impacts. Future studies exploring the underlying mechanisms linking brain ageing and metabolic dysregulation may provide valuable insights into the complex pathophysiology of these conditions and the increased vulnerability of schizophrenia patients to severe outcomes.

Metabolism changes caused by glucose in normal and cancer human brain cell lines by Raman imaging and chemometric methods

Glucose is the main source of energy for the human brain. This paper presents a non-invasive technique to study metabolic changes caused by glucose in human brain cell lines. In this paper we present the spectroscopic characterization of human normal brain (NHA; astrocytes) and human cancer brain (CRL-1718; astrocytoma and U-87 MG; glioblastoma) control cell lines and cell lines upon supplementation with glucose. Based on Raman techniques we have identified biomarkers that can monitor metabolic changes in lipid droplets, mitochondria and nucleus caused by glucose. We have studied the vibrations at 750 cm−1, 1444 cm−1, 1584 cm−1 and 1656 cm−1 as a function of malignancy grade. We have compared the concentration of cytochrome, lipids and proteins in the grade of cancer aggressiveness in normal and cancer human brain cell lines. Chemometric analysis has shown that control normal, control cancer brain cell lines and normal and cancer cell lines after supplementation with glucose can be distinguished based on their unique vibrational properties. PLSDA (Partial Least Squares Discriminant Analysis) and ANOVA tests have confirmed the main role of cytochromes, proteins and lipids in differentiation of control human brain cells and cells upon supplementation with glucose. We have shown that Raman techniques combined with chemometric analysis provide additional insight to monitor the biology of astrocytes, astrocytoma and glioblastoma after glucose supplementation.

Evolutionary origin of the chordate nervous system revealed by amphioxus developmental trajectories.

The common ancestor of all vertebrates had a highly sophisticated nervous system, but questions remain about the evolution of vertebrate neural cell types. The amphioxus, a chordate that diverged before the origin of vertebrates, can inform vertebrate evolution. Here we develop and analyse a single-cell RNA-sequencing dataset from seven amphioxus embryo stages to understand chordate cell type evolution and to study vertebrate neural cell type origins. We identified many new amphioxus cell types, including homologues to the vertebrate hypothalamus and neurohypophysis, rooting the evolutionary origin of these structures. On the basis of ancestor-descendant reconstruction of cell trajectories of the amphioxus and other species, we inferred expression dynamics of transcription factor genes throughout embryogenesis and identified three ancient developmental routes forming chordate neurons. We characterized cell specification at the mechanistic level and generated mutant lines to examine the function of five key transcription factors involved in neural specification. Our results show three developmental origins for the vertebrate nervous system: an anterior FoxQ2-dependent mechanism that is deeply conserved in invertebrates, a less-conserved route leading to more posterior neurons in the vertebrate spinal cord and a mechanism for specifying neuromesoderm progenitors that is restricted to chordates. The evolution of neuromesoderm progenitors may have led to a dramatic shift in posterior neural and mesodermal cell fate decisions and the body elongation process in a stem chordate.

Age-related energetic reprogramming in glial cells: possible correlations with Parkinson’s disease

Glial cells populate the central nervous system and undertake indispensable roles in safeguarding and maintaining optimal neuronal performance. Throughout life, the brain undergoes inevitable changes that impact both neurons and glial cells. Concurrent with age-related neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), metabolic dysfunctions in glial cells are consistently observed. Though widely debated, the idea of treating neurodegenerative disorders by manipulating brain bioenergetics warrants further exploration. This review discusses the distinctive metabolic characteristics of central nervous system (CNS) glia, the metabolic deviations that occur in glial cells in the aging brain, and the ramifications of metabolic rewiring within glia on neurodegenerative disorders, specifically PD. We focus on astrocytes and microglia due to their substantial transformations under aging and diseased states, known as reactivation. Special attention is given to clarifying the complex relationships between dysregulated glial energy metabolism and brain disorders. By discussing both classic theories and current advances in this field, we aim to shed light on promising therapeutic horizons anchored in the strategic calibration of glial metabolic configurations.

Acylhydrazone Derivative A5 Promotes Neurogenesis by Up-Regulating Neurogenesis-Related Genes and Inhibiting Cell-Cycle Progression in Neural Stem/Progenitor Cells

Adult neurogenesis involves the generation of functional neurons from neural progenitor cells, which have the potential to complement and restore damaged neurons and neural circuits. Therefore, the development of drugs that stimulate neurogenesis represents a promising strategy in stem cell therapy and neural regeneration, greatly facilitating the reconstruction of neural circuits in cases of neurodegeneration and brain injury. Our study reveals that compound A5, previously designed and synthesized by our team, exhibits remarkable neuritogenic activities, effectively inducing neurogenesis in neural stem/progenitor cells (NSPCs). Subsequently, transcriptome analysis using high-throughput Illumina RNA-seq technology was performed to further elucidate the underlying molecular mechanisms by which Compound A5 promotes neurogenesis. Notably, comparative transcriptome analysis showed that the up-regulated genes were mainly associated with neurogenesis, and the down-regulated genes were mainly concerned with cell cycle progression. Furthermore, we confirmed that Compound A5 significantly affected the expression of transcription factors related to neurogenesis and cell cycle regulatory proteins. Collectively, these findings identify a new compound with neurogenic activity and may provide insights into drug discovery for neural repair and regeneration.

Umbilical cord blood stem cells: transplantation prospects in neurological practice

Umbilical cord blood has evolved from being considered a mere cellular/tissue waste product after childbirth to a valuable biological material with a wide regenerative potential. Today, hematopoietic cord blood stem cells are used in the same way as bone marrow and mobilised peripheral blood as part of the standard medical treatment for haemoblastoses and hereditary blood diseases. There is an increasing amount of experimental data showing possibility of umbilical cord blood cell fractions using for treatment of non-hematological diseases and, in particular, diseases of the central nervous system. One of the key challenges in cell therapy for central nervous system diseases is the choice of cellular material for neurotransplantation. This is particularly relevant for ischemic and traumatic injuries, as well as neurodegenerative diseases. Stem or mature somatic cells prepared for neurotransplantation should have predictable and reproducible characteristics thataccording therapeutic purposes, exactly: trophic and/or neuroprotective action to increase neurons viability in damaged area; axon growth stimulation and myelination; cell matrix restoration or predictable differentiation direction to replace amount of lost brain or spinal cord cells. The fact that umbilical cord blood contains not only hematopoietic, but also various non-hematopoietic stem cells with a wide regenerative potential has become the basis for active use of these cells for neurotransplantation. The proposed review provides historical information about umbilical cord blood introduction into practical medicine, its cellular composition and clinical applications of stem cells various types for children central nervous system diseases treatment, such as ischemic encephalopathy, stroke, cerebral hemorrhage, cerebral palsy, autism, and in adults — for stroke treatment, spinal cord injury and neurodegenerative diseases.

Designing efficient brain tumor classifier using hybrid EfficientNet-faster R-CNN deep learning model

Abstract Purpose: Brain tumors have historically posed a significant risk to individuals, potentially leading to fatality. However, in contemporary times, they have emerged as one of the most dangerous health issues affecting both children and adults. The effects of this phenomenon result in the unregulated proliferation of brain cells. Within the field of biological image processing, the utilisation of deep learning algorithms offers a distinct and unparalleled experience. The Convolutional Neural Network (CNN) is a pivotal component in brain tumor categorization applications. However, a notable limitation of CNNs is their extensive execution time, primarily attributed to the substantial number of trainable parameters involved. 
Methods: This study proposes a hybrid model for brain tumor classification that combines faster R-CNN and EfficientNet. The objective is to minimise the time required for classification without compromising accuracy. The data collection from Figshare was employed during the model's development.
Results and Conclusion: The hybrid model proposed in this study demonstrates a notable accuracy of 98.96% during the training phase and 99.2% during the testing phase, surpassing the performance of both the EfficientNet model and the Faster R-CNN model when employed individually. The aforementioned findings were derived through a comparative analysis of the Hybrid model, the EfficientNet model, and the Faster R-CNN model.

Are the promnestic effects of neurokinin 3 receptor mediated by hippocampal neurogenesis in a Aβ-induced rat model of Alzheimer's disease?

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterised by cognitive dysfunction, memory loss and mood changes. Hippocampal neurogenesis has been suggested to play a role in learning and memory. Neurokinin 3 receptor (NK3R) has been shown to be prevalent in the hippocampus region. The aim of the project was to investigate the role of hippocampal neurogenesis in the promnestic effects of NK3R agonist administration in an amyloid beta-induced AD rat model. Wistar albino rats were divided into control, Alzheimer, NK3R agonist and Alzheimer + NK3R agonist groups. The open field (OF) test and Morris water maze (MWM) test were performed for locomotor activity and memory analysis. Peptide gene expression levels (Nestin, DCX, Neuritin, MASH1, Neun, BDNF) were analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR). In the OF test, the group-time relationship was found to be statistically different in the parameters of distance travelled and percentage of movement (p< 0.05). In MWM, the time to reach the platform and the time spent in the target quadrant were statistically significant between the groups (p< 0.05). Statistically significant differences were observed in gene expression levels (Nestin, DCX, Neuritin, MASH1) in the hippocampal tissue of rats between the groups (p< 0.05). NK3 receptor agonism favourably affected hippocampal neurogenesis in AD model rats. It was concluded that NK3 receptor agonism in the hippocampus, which is the first affected region in the physiopathology of AD, may be effective in both the formation of neural precursor cells and the reduction of neuronal degeneration. The positive effect of NK3R on cognitive functions may be mediated by hippocampal neurogenesis.

Assembling a coculture system to prepare highly pure induced pluripotent stem cell-derived neurons at late maturation stages.

Generation of human induced pluripotent stem cell (hiPSC)-derived motor neurons (MNs) offers an unprecedented approach to modeling movement disorders such as dystonia and amyotrophic lateral sclerosis. However, achieving survival poses a significant challenge when culturing induced MNs, especially when aiming to reach late maturation stages. Utilizing hiPSC-derived motor neurons and primary mouse astrocytes, we assembled two types of coculture systems: direct coculturing of neurons with astrocytes, and indirect coculture using culture inserts that physically separate neurons and astrocytes. Both systems significantly enhance neuron survival. Compared with these two systems, no significant differences in neurodevelopment, maturation, and survival within 3 weeks, allowing to prepare neurons at maturation stages. Using the indirect coculture system, we obtained highly pure MNs at the late mature stage from hiPSCs. Transcriptomic studies of hiPSC-derived MNs showed a typical neurodevelopmental switch in gene expression from the early immature stage to late maturation stages. Mature genes associated with neurodevelopment and synaptogenesis are highly enriched in MNs at late stages, demonstrating that these neurons achieve maturation. This study introduces a novel tool for the preparation of highly pure hiPSC-derived neurons, enabling the determination of neurological disease pathogenesis in neurons at late disease onset stages through biochemical approaches, which typically necessitate highly pure neurons. This advancement is particularly significant in modeling age-related neurodegeneration.Significance Statement Achieving survival poses a significant challenge for long-term neural cell cultures. Utilizing hiPSC-derived motor neurons and primary mouse astrocytes, we established an indirect coculture system using culture inserts that physically separate neurons and astrocytes, thereby facilitating neuronal maturation. Transcriptomic studies revealed the typical neurodevelopmental switch in gene expression from the early immature stage to late maturation stages, indicating the high quality and maturation of neurons prepared with culture inserts. This study introduces a novel tool for the preparation of highly pure hiPSC-derived neurons, enabling the determination of neurological disease pathogenesis in neurons at late disease onset stages through biochemical approaches, which typically necessitate highly pure neurons. This advancement is particularly significant in modeling age-related neurodegeneration.

Application of GWAS summary data and drug-induced gene expression profiles of neural progenitor cells in psychiatric drug prioritization analysis.

Common psychiatric disorders constitute one of the most substantial healthcare burdens worldwide. However, drug development in psychiatry remains hampered partiallydue to the lack of approaches to estimating drugs that can simultaneously modulate the expression of a nontrivial fraction of disease susceptibility genes. We proposed a new drug prioritization strategy under the framework of our previously proposed phenotype-associated tissues estimation approach (DESE) by investigating the drugs' selective perturbation effect on disease susceptibility genes. Based on the genome-wide association study summary data and drug-induced gene expression profiles of neural progenitor cells, we applied this strategy to prioritize candidate drugs for schizophrenia, depression and bipolar I disorder and identified several known therapeutic drugs among the top-ranked drug candidates. Also, our results revealed that the disease susceptibility genes involved in the selective gene perturbation analysis were enriched with many biologically sensible function terms and interacted with known therapeutic drugs. Our results suggested that selective gene perturbation analysis could be a promising starting point to prioritize biologically sensible drug candidates under the "one drug, multiple targets" paradigm for the drug development of common psychiatric disorders.

Editorial: Space and neural cell: the impact of space environment on neurological function and their molecular mechanistic insights

Editorial: Space and neural cell: the impact of space environment on neurological function and their molecular mechanistic insights

Insights into Brominated Flame Retardant Neurotoxicity: Mechanisms of Hippocampal Neural Cell Death and Brain Region-Specific Transcriptomic Shifts in Mice.

Brominated Flame Retardants (BFRs) reduce flammability in a wide range of products including electronics, carpets, and paint, but leach into the environment to result in continuous, population-level exposure. Epidemiology studies have correlated BFR exposure with neurological problems, including alterations in learning and memory. This study investigated the molecular mechanisms mediating BFR-induced cell death in hippocampal cells and clarified the impact of HBCD exposure on gene transcription in the hippocampus, dorsal striatum, and frontal cortex of male mice. Exposure of hippocampus derived HT-22 cells to various flame retardants, including tetrabromobisphenol-A (TBBPA, current use), hexabromocyclododecane (HBCD, phasing out), or 2,2',4,4'-tetrabromodiphenyl ether (BDE-47, phased out) resulted in time, concentration, and chemical-dependent cellular and nuclear morphology alterations, alterations in cell cycle and increases in annexin V staining. All three BFRs increased p53 and p21 expression; however, inhibition of p53 nuclear translocation using pifthrin-α did not decrease cell death. Transcriptomic analysis upon low (10 nM) and cytotoxic (10 μM) BFR exposure indicated that HBCD and BDE-47 altered genes mediating autophagy-related pathways. Further evaluation showed BFR exposure increased LC3-II conversion and autophagosome formation, and co-exposure with the autophagy inhibitor 3-methyladenine (3-MA) attenuated cytotoxicity. Transcriptomic assessment of select brain regions from subchronically HBCD-exposed male mice demonstrated alteration of genes mediating vesicular transport, with greater impact on the frontal cortex and dorsal striatum compared to the dorsal and ventral hippocampus. Immunoblot analysis demonstrated no increases in cell death or autophagy markers, but did demonstrate increases in the SNARE binding complex SNAP29, specifically in the dorsal hippocampus. These data demonstrate that BFRs can induce chemical-dependent autophagy in neural cells in vitro and provide evidence that BFRs induce region-specific transcriptomic and protein expression in the brain suggestive of change in vesicular trafficking.

Exploring the origins of neurodevelopmental proteasomopathies associated with cardiac malformations: are neural crest cells central to certain pathological mechanisms?

Exploring the origins of neurodevelopmental proteasomopathies associated with cardiac malformations: are neural crest cells central to certain pathological mechanisms?

Gestational bisphenol A exposure alters energy homeostasis and adult hypothalamic neurogenesis in female mice

Regulation of physiological homeostasis, including energy balance, is thought to be modified by low levels of adult neurogenesis in the hypothalamus. Hormones such as oestradiol can influence both embryonic and adult hypothalamic neurogenic programs, demonstrating a sensitivity of hypothalamic neural progenitor cells to endogenous hormones. Previously we showed that gestational exposure to environmental levels of the xenoestrogen bisphenol A (BPA) changed neural progenitor cell behaviors in the embryo; however, we did not examine if these changes were permanent to affect adult neurogenesis. Here we investigated whether adult neuro- and/or gliogenesis were altered in mice prenatally exposed to BPA and placed on a high-fat diet challenge. Gestationally exposed adult female mice on a standard diet gained less weight than non-BPA controls, whereas gestationally exposed BPA females on a high-fat diet gained more weight than controls. Males exposed to gestational BPA showed no differences in weight gain relative to control males. Concomitantly, adult neurogenesis was increased in the VMH, DMH, and PVN of adult female mice exposed to BPA on standard diet, suggesting that disrupted adult neurogenesis might perturb normal energy balance regulation in females. These results add to growing evidence that low-dose BPA exposure in utero causes changes to adult hypothalamic function.