Uncovering the role of the subcommissural organ in early brain development through transcriptomic analysis.

BACKGROUND: The significant role of embryonic cerebrospinal fluid (eCSF) in the initial stages of brain development has been thoroughly studied. This fluid contains crucial molecules for proper brain development such as members of the Wnt and FGF families, apolipoproteins, and retinol binding protein. Nevertheless, the source of these molecules remains uncertain since they are present before the formation of the choroid plexus, which is conventionally known as the primary producer of cerebrospinal fluid. The subcommissural organ (SCO) is a highly conserved gland located in the diencephalon and is one of the earliest differentiating brain structures. The SCO secretes molecules into the eCSF, prior to the differentiation of the choroid plexus, playing a pivotal role in the homeostasis and dynamics of this fluid. One of the key molecules secreted by the SCO is SCO-spondin, a protein involved in maintenance of the normal ventricle size, straight spinal axis, neurogenesis, and axonal guidance. Furthermore, SCO secretes transthyretin and basic fibroblast growth factor 2, while other identified molecules in the eCSF could potentially be secreted by the SCO. Additionally, various transcription factors have been identified in the SCO. However, the precise mechanisms involved in the early SCO development are not fully understood. RESULTS: To uncover key molecular players and signaling pathways involved in the role of the SCO during brain development, we conducted a transcriptomic analysis comparing the embryonic chick SCO at HH23 and HH30 stages (4 and 7 days respectively). Additionally, a public transcriptomic data from HH30 entire chick brain was used to compare expression levels between SCO and whole brain transcriptome. These analyses revealed that, at both stages, the SCO differentially expresses several members of bone morphogenic proteins, Wnt and fibroblast growth factors families, diverse proteins involved in axonal guidance, neurogenic and differentiative molecules, cell receptors and transcription factors. The secretory pathway is particularly upregulated at stage HH30 while the proliferative pathway is increased at stage HH23. CONCLUSION: The results suggest that the SCO has the capacity to secrete several morphogenic molecules to the eCSF prior to the development of other structures, such as the choroid plexus.

SARS-CoV-2-associated cytokine storm during pregnancy as a possible risk factor for neuropsychiatric disorder development in post-pandemic infants.

A strong association between perinatal viral infections and neurodevelopmental disorders has been established. Both the direct contact of the virus with the developing brain and the strong maternal immune response originated by viral infections can impair proper neurodevelopment. Coronavirus disease 2019 (COVID-19), caused by the highly-infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is currently responsible for a large global outbreak and is a major public health issue. While initial studies focused on the viral impact on the respiratory system, increasing evidence suggest that SARS-CoV-2 infects other organs and tissues including the mature brain. While studies continue to determine the neuropathology associated to COVID-19, the consequences of SARS-CoV-2 infection to the developing brain remain largely unexplored. The present review discusses evidence suggesting that SARS-CoV-2 infection may have persistent effects on the course of pregnancy and on brain development. Studies have shown that several proinflammatory mediators which are increased in the SARS-CoV-2-associated cytokine storm, are also modified in other viral infections known to increase the risk of neurodevelopmental disorders. In this sense, further studies should assess the genuine effects of SARS-CoV-2 infection during pregnancy and delivery along with an extended follow-up of the offspring, including neurocognitive, neuroimaging, and electrophysiological examination. It also remains to be determined whether and by which mechanisms SARS-CoV-2 intrauterine and early life infection could lead to an increased risk of developing neuropsychiatric disorders, such as autism (ASD) and schizophrenia (SZ), in the offspring.

The clinical spectrum and immunopathological mechanisms underlying ZIKV-induced neurological manifestations.

Since the 2015 to 2016 outbreak in America, Zika virus (ZIKV) infected almost 900,000 patients. This international public health emergency was mainly associated with a significant increase in the number of newborns with congenital microcephaly and abnormal neurologic development, known as congenital Zika syndrome (CZS). Furthermore, Guillain-Barré syndrome (GBS), a neuroimmune disorder of adults, has also been associated with ZIKV infection. Currently, the number of ZIKV-infected patients has decreased, and most of the cases recently reported present as a mild and self-limiting febrile illness. However, based on its natural history of a typical example of reemerging pathogen and the lack of specific therapeutic options against ZIKV infection, new outbreaks can occur worldwide, demanding the attention of researchers and government authorities. Here, we discuss the clinical spectrum and immunopathological mechanisms underlying ZIKV-induced neurological manifestations. Several studies have confirmed the tropism of ZIKV for neural progenitor stem cells by demonstrating the presence of ZIKV in the central nervous system (CNS) during fetal development, eliciting a deleterious inflammatory response that compromises neurogenesis and brain formation. Of note, while the neuropathology of CZS can be due to a direct viral neuropathic effect, adults may develop neuroimmune manifestations such as GBS due to poorly understood mechanisms. Antiganglioside autoantibodies have been detected in multiple patients with ZIKV infection-associated GBS, suggesting a molecular mimicry. However, further additional immunopathological mechanisms remain to be uncovered, paving the way for new therapeutic strategies.

Histopathological lesions of congenital Zika syndrome in newborn squirrel monkeys.

The absence of an adequate animal model for studies has limited the understanding of congenital Zika syndrome (CZS) in humans during the outbreak in America. In this study, we used squirrel monkeys (Saimiri collinsi), a neotropical primate (which mimics the stages of human pregnancy), as a model of Zika virus (ZIKV) infection. Seven pregnant female squirrel monkeys were experimentally infected at three different gestational stages, and we were able reproduce a broad range of clinical manifestations of ZIKV lesions observed in newborn humans. Histopathological and immunohistochemical analyses of early-infected newborns (2/4) revealed damage to various areas of the brain and ZIKV antigens in the cytoplasm of neurons and glial cells, indicative of CZS. The changes caused by ZIKV infection were intrauterine developmental delay, ventriculomegaly, simplified brain gyri, vascular impairment and neuroprogenitor cell dysfunction. Our data show that the ZIKV infection outcome in squirrel monkeys is similar to that in humans, indicating that this model can be used to help answer questions about the effect of ZIKV infection on neuroembryonic development and the morphological changes induced by CZS.

Segregation of brain and organizer precursors is differentially regulated by Nodal signaling at blastula stage.

The blastula Chordin- and Noggin-expressing (BCNE) center comprises animal-dorsal and marginal-dorsal cells of the amphibian blastula and contains the precursors of the brain and the gastrula organizer. Previous findings suggested that the BCNE behaves as a homogeneous cell population that only depends on nuclear ß-catenin activity but does not require Nodal and later segregates into its descendants during gastrulation. In contrast to previous findings, in this work, we show that the BCNE does not behave as a homogeneous cell population in response to Nodal antagonists. In fact, we found that chordin.1 expression in a marginal subpopulation of notochordal precursors indeed requires Nodal input. We also establish that an animal BCNE subpopulation of cells that express both, chordin.1 and sox2 (a marker of pluripotent neuroectodermal cells), and gives rise to most of the brain, persisted at blastula stage after blocking Nodal. Therefore, Nodal signaling is required to define a population of chordin.1+ cells and to restrict the recruitment of brain precursors within the BCNE as early as at blastula stage. We discuss our findings in Xenopus in comparison to other vertebrate models, uncovering similitudes in early brain induction and delimitation through Nodal signaling.

Central nervous system development in rabbits (Oryctolagus cuniculus L. 1758).

The present study describes the embryonic and fetal development of the central nervous system in rabbits from the seventh day after conception until the end of the full-term fetal period. A total of 19 embryonic and fetal samples were carefully dissected and microscopically analyzed. Neural tube closure was observed between 7.5 and 8 days of gestation. Primordial encephalic vesicle differentiation and spinal canal delimitation were observed on the 12th day of gestation. Histologically, on the 15th day of gestation, the brain, cerebellum, and brain stem were delimited. On the 18th day of gestation, the cervical and lumbar intumescences of the spinal cord were visible. On the 28th day of gestation, four-cell layers could be distinguished in the cerebral cortex, while the cerebellar cortex was still differentiating. Overall, the morphological aspects of the embryonic and fetal developmental phases in rabbits were highly similar to those in humans. Thus, the present study provides relevant information highlighting rabbits as an excellent candidate animal model for preclinical research on human neurological diseases given the high adaptability of rabbits to bioterium conditions and the similarity of morphological events between rabbits and humans.

Ontogeny of the brain of Microglanis garavelloi Shibatta and Benine 2005 (Teleostei: Siluriformes: Pseudopimelodidae).

The gross brain morphology and the peripheral olfactory organ of Microglanis garavelloi are described throughout development, and the relationship of these organs to the general behaviour of the species is discussed. During the development, the main brain subdivisions undergo a series of morphological changes keeping a relatively constant volume increase. However, we observed different growth rates in the brains of males and females when these were compared. During the maturation process, a series of hormonal events result in the development of some secondary sexual traits in the brain of male specimens, like faster growth rate of brain areas linked to motor control, olfactory and visual responses. The number of olfactory-organ lamellae increases continuously in both males and females, during their maturation period. These results suggest that changes may be caused by cognitive demands that this species is exposed to throughout its lifespan. The gross morphological arrangement of the central nervous system indicates shared patterns with other members of the family Pseudopimelodidae.

Expression of Pax6 and Pax7 proteins during the central nervous system development in human embryos / Expresión de proteínas Pax6 y Pax7 durante el desarrollo del sistema central nervioso en embriones humanos

The family of paired box (Pax) genes encodes the transcription factors that have been emphasized for the particular importance to embryonic development of the CNS, with the evidence obtained from various animal models. Human embryos have rarely been available for the detection of the expression of Pax family members. In this study 32 human embryos of Carnegie (CS) stages 10-20 were investigated to find the differences in the expression of Pax6 and Pax7 proteins in different regions of the neural tube and the caudal spinal cord. The expression of Pax6 and Pax7, as determined by immunohistochemistry, showed a tendency to increase in the later stages of the development both in the spinal cord and the brain. Significantly weaker expression of Pax6 and Pax7 was observed at CS 10 as compared to the later stages. At CS 10-12 weak expression of Pax6 was noticed in both dorsal and ventral parts of the developing spinal cord, while the expression of Pax7 was restricted to the cells in the roof plate and the dorsal part of the spinal cord. At CS 14-20 in the developing spinal cord Pax6 and Pax7 were detected mostly in the neuroepithelial cells of the ventricular layer, while only weak expression characterized the mantle and the marginal layers. At the same stages in the developing brain Pax6 and Pax7 were expressed in the different regions of the forebrain, the midbrain and the hindbrain suggesting for their involvement in the differentiation of neurons in specific parts of the developing brain.

La familia de genes Pax del inglés (Paired box) codifica los factores de transcripción debido a la particular importancia en el desarrollo embrionario del SNC, con la evidencia obtenida de varios modelos animales. Rara vez han estado disponibles embriones humanos para la detección de la expresión de genes de la familia Pax. En este estudio, se investigaron 32 embriones humanos de Carnegie (CS) etapas 10-20 para encontrar las diferencias en la expresión de las proteínas Pax6 y Pax7 en diferentes regiones del tubo neural y la médula espinal caudal. La expresión de Pax6 y Pax7, según la inmunohistoquímica, se observó una tendencia a aumentar en las etapas posteriores del desarrollo, tanto en la médula espinal como en el cerebro. Se observó una expresión significativamente más débil de Pax6 y Pax7 en CS 10 en comparación con las etapas posteriores. En CS 10-12 se notó una expresión débil de Pax6 en las partes dorsal y ventral de la médula espinal en desarrollo, mientras que la expresión de Pax7 se limitó a células en la placa del techo y dorsal de la médula espinal. En CS 14-20 en la médula espinal en desarrollo, Pax6 y Pax7 se observó principalmente en las células neuroepiteliales de la capa ventricular, mientras que expresión débil se caracterizó en las capas marginales. En las mismas etapas en el cerebro en desarrollo, Pax6 y Pax7 se expresaron en las diferentes áreas del prosencéfalo, el mesencéfalo y el mesencéfalo, lo que sugiere su participación en la diferenciación de las neuronas en partes específicas del cerebro en desarrollo.

The journey of Zika to the developing brain.

Zika virus is a mosquito-borne Flavivirus originally isolated from humans in 1952. Following its re-emergence in Brazil in 2015, an increase in the number of babies born with microcephaly to infected mothers was observed. Microcephaly is a neurodevelopmental disorder, characterised phenotypically by a smaller than average head size, and is usually developed in utero. The 2015 outbreak in the Americas led to the World Health Organisation declaring Zika a Public Health Emergency of International Concern. Since then, much research into the effects of Zika has been carried out. Studies have investigated the structure of the virus, its effects on and evasion of the immune response, cellular entry including target receptors, its transmission from infected mother to foetus and its cellular targets. This review discusses current knowledge and novel research into these areas, in hope of developing a further understanding of how exposure of pregnant women to the Zika virus can lead to impaired brain development of their foetus. Although no longer considered an epidemic in the Americas, the mechanism by which Zika acts is still not comprehensively and wholly understood, and this understanding will be crucial in developing effective vaccines and treatments.

Clinical and subclinical maternal hypothyroidism and their effects on neurodevelopment, behavior and cognition.

Clinical and subclinical hypothyroidism are the most common hormonal dysfunctions during pregnancy. Insufficient maternal thyroid hormones (THs) in the early stages of pregnancy can lead to severe impairments in the development of the central nervous system because THs are critical to central nervous system development. In the fetus and after birth, THs participate in neurogenic processes, cell differentiation, neuronal activation, axonal growth, dendritic arborization, synaptogenesis and myelination. Although treatment is simple and effective, approximately 30% of pregnant women in Brazil with access to prenatal care have their first consultation after the first trimester of pregnancy, and any delay in diagnosis and resulting treatment delay may lead to cognitive impairment in children. This review summarizes the effects of clinical and subclinical hypothyroidism on fetal neurodevelopment, behavior and cognition in humans and rodents. Arch Endocrinol Metab. 2020;64(1):89-95.

Probabilistic Learning Coherent Point Drift for 3D Ultrasound Fetal Head Registration.

Quantification of brain growth is crucial for the assessment of fetal well being, for which ultrasound (US) images are the chosen clinical modality. However, they present artefacts, such as acoustic occlusion, especially after the 18th gestational week, when cranial calcification appears. Fetal US volume registration is useful in one or all of the following cases: to monitor the evolution of fetometry indicators, to segment different structures using a fetal brain atlas, and to align and combine multiple fetal brain acquisitions. This paper presents a new approach for automatic registration of real 3D US fetal brain volumes, volumes that contain a considerable degree of occlusion artefacts, noise, and missing data. To achieve this, a novel variant of the coherent point drift method is proposed. This work employs supervised learning to segment and conform a point cloud automatically and to estimate their subsequent weight factors. These factors are obtained by a random forest-based classification and are used to appropriately assign nonuniform membership probability values of a Gaussian mixture model. These characteristics allow for the automatic registration of 3D US fetal brain volumes with occlusions and multiplicative noise, without needing an initial point cloud. Compared to other intensity and geometry-based algorithms, the proposed method achieves an error reduction of 7.4% to 60.7%, with a target registration error of only 6.38 ± 3.24 mm. This makes the herein proposed approach highly suitable for 3D automatic registration of fetal head US volumes, an approach which can be useful to monitor fetal growth, segment several brain structures, or even compound multiple acquisitions taken from different projections.

Clinical and subclinical maternal hypothyroidism and their effects on neurodevelopment, behavior and cognition

ABSTRACT Clinical and subclinical hypothyroidism are the most common hormonal dysfunctions during pregnancy. Insufficient maternal thyroid hormones (THs) in the early stages of pregnancy can lead to severe impairments in the development of the central nervous system because THs are critical to central nervous system development. In the fetus and after birth, THs participate in neurogenic processes, cell differentiation, neuronal activation, axonal growth, dendritic arborization, synaptogenesis and myelination. Although treatment is simple and effective, approximately 30% of pregnant women in Brazil with access to prenatal care have their first consultation after the first trimester of pregnancy, and any delay in diagnosis and resulting treatment delay may lead to cognitive impairment in children. This review summarizes the effects of clinical and subclinical hypothyroidism on fetal neurodevelopment, behavior and cognition in humans and rodents. Arch Endocrinol Metab. 2020;64(1):89-95

Patterns of spon1b:GFP expression during early zebrafish brain development.

OBJECTIVE: F-spondin is part of a group of evolutionarily conserved extracellular matrix proteins in vertebrates. It is highly expressed in the embryonic floor plate, and it can bind to the ECM and promote neuronal outgrowth. A characterization of F-spondin expression patterns in the adult zebrafish brain was previously reported by our group. However, given its importance during development, we aimed to obtain a detailed description of green fluorescent protein (GFP) expression driven by the spon1b promotor, in the developing zebrafish brain of the transgenic Tg(spon1b:GFP) line, using light sheet fluorescence microscopy (LSFM). RESULTS: Images obtained in live embryos from 22 to 96 h post fertilization confirmed our earlier reports on the presence of spon1b:GFP expressing cells in the telencephalon and diencephalon (olfactory bulbs, habenula, optic tectum, nuclei of the medial longitudinal fasciculus), and revealed new spon1b:GFP populations in the pituitary anlage, dorso-rostral cluster, and ventro-rostral cluster. LSFM made it possible to follow the dynamics of cellular migration patterns during development. CONCLUSIONS: spon1b:GFP larval expression patterns starts in early development in specific neuronal structures of the developing brain associated with sensory-motor modulation. LSFM evaluation of the transgenic Tg(spon1b:GFP) line provides an effective approach to characterize GFP expression patterns in vivo.

An Unusual First-Trimester Ultrasound Presentation of the Acrania-Anencephaly Sequence: The "Turkish Turban" Sign.

A previously unrecognized first-trimester presentation of the acrania-anencephaly sequence is described. Ultrasound features included a constriction ring around the external base of the developing skull and an enlarged globular head, resembling a Turkish turban, with large cystic spaces replacing the brain. This constellation of findings was noted in 3 first-trimester fetuses. In 2 of them, it was possible to identify the amniotic membrane attached to the constriction ring. One case presented with anencephaly and fetal demise at 16 weeks. The other 2 women terminated the pregnancies and aborted anencephalic fetuses. This subtype of the acrania-anencephaly sequence could represent an earlier segmental rupture of the amnion, which subsequently entraps the developing fetal skull.

Maternal physical activity-induced adaptive transcriptional response in brain and placenta of mothers and rat offspring.

Maternal physical activity induces brain functional changes and neuroplasticity, leading to an improvement of cognitive functions, such as learning and memory in the offspring. This study investigated the effects of voluntary maternal physical activity on the gene expression of the neurotrophic factors (NTFs): BDNF, NTF4, NTRK2, IGF-1 and IGF-1r in the different areas of mother's brain, placenta and foetus brain of rats. Female Wistar rats (n = 15) were individually housed in voluntary physical activity cages, containing a running wheel, for 4 weeks (period of adaptation) before gestation. Rats were classified as inactive (I, n = 6); active (A, n = 4) and very active (VA, n = 5) according to daily distance spontaneously travelled. During gestation, the dams continued to have access to the running wheel. At the 20th day of gestation, gene expression of NTFs was analysed in different areas of mother's brain (cerebellum, hypothalamus, hippocampus and cortex), placenta and the offspring's brain. NTFs gene expression was evaluated using quantitative PCR. Very active mothers showed upregulation of IGF-1 mRNA in the cerebellum (36.8%) and NTF4 mRNA expression in the placenta (24.3%). In the cortex, there was a tendency of up-regulation of NTRK2 mRNA (p = 0.06) in the A and VA groups when compared to I group. There were no noticeable changes in the gene expression of NTFs in the offspring's brain. Our findings suggest the existence of a developmental plasticity induced by maternal physical activity in specific areas of the brain and placenta representing the first investment for offspring during development.

Vesicles stage of camel brain development / Etapas del desarrollo de las vesículas cerebrales del camello

A successive embryonic developmental study was conducted on the brain of twenty eight embryos and fetuses of one humped camel (Camelus Dromedarius), whose crown vertebral rump lengths (CVRL) ranged from 9 to 80 mm, collected from the El-Basateen (Cairo) and Belbees (ElSharqya) Slaughterhouse. The current investigation revealed that camel brain was found to consist of fore, mid and hind brains. The fore brain is divided into telencephalon and diencephalon while the rhombencephalon divided into metencephalon and myelencephalon. Flexures appeared between the vesicles are cervical flexure between the rhomencephalon and the spinal cord, cephalic flexure in the mesencephalon and pontine flexure between the metencephalon, and the myelencephalon of the hind brain (rhombencephalon). The cavity of the rhombencephalon is the fourth ventricle, while that of the diencephalon is the third ventricle, and those of the telencephalon are the lateral ventricles but that of mid brain is the cerebral aqueduct. myelencephalon becomes medulla oblongata and metencephalon developed to pons and cerebellum while mesencephalon gives rise to the cerebral crura and anterior and a posterior colliculus. Diencephalon gives the thalamus, hypothalamus, mamillary body, infundibulum and pineal body while telencephalon becomes the cerebral hemispheres and corpus striatum.

Se llevó a cabo un estudio del desarrollo embrionario cerebral de veintiocho embriones y fetos de camello jorobado (Camelus dromedarius). Las muestras fueron recolectadas en los mataderos de El-Basateen (El Cairo) y Belbees (ElSharqya). La investigación reveló que el cerebro de camello posee un cerebro anterior, medio y posterior. El cerebro anterior se divide en telencéfalo y diencéfalo, mientras que el rombencéfalo se divide en metencéfalo y mielencéfalo. Las flexiones encontradas entre las vesículas son la flexión cervical entre el rombencéfalo y la médula espinal; la flexión cefálica en el mesencéfalo; y la flexión pontina entre el metencéfalo y el mielencéfalo del cerebro posterior (rombencéfalo). La cavidad del rombencéfalo conforma el cuarto ventrículo, la del diencéfalo forma el tercer ventrículo, y las del telencéfalo a los ventrículos laterales. En el cerebro medio, la cavidad corresponde al acueducto cerebral. El mielencéfalo se convierte en médula oblonga y el metencéfalo deriva en puente y cerebelo, mientras que el mesencéfalo da lugar a la crura cerebral y a los colículos anterior y posterior. El diencéfalo origina el tálamo, el hipotálamo, el cuerpo mamilar, el infundíbulo y la hipófisis, mientras que del telencéfalo se originan los hemisferios cerebrales y el cuerpo estriado.

Exposure to homocysteine leads to cell cycle damage and reactive gliosis in the developing brain.

Studies that investigate the cellular effects of homocysteine (Hcy) on the differentiation of neural cells, and their involvement in establishment of cell layers in the developing brain are scarce. This study evaluated how Hcy affects the neural cell cycle and proteins involved in neuronal differentiation in the telencephalon and mesencephalon using the chicken embryo as a model. Embryos at embryonic day 2 (E2) received 20 µmol D-L Hcy/50 µl saline and analyzed at E6. The Hcy treatment induced an increase in the ventricular length of the telencephalon and also a reduction of the mantle layer thickness. We observed that Hcy induced impairments to the neural cell cycle and differentiation, which compromised the cell layers establishment in the developing brain. Hcy treatment also induced changes in gene and protein expression of astrocytes, characteristic of reactive gliosis. Our results point to new perspectives of evaluation of cellular targets of Hcy toxicity.

ADGRL3 rs6551665 as a Common Vulnerability Factor Underlying Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder.

Neurodevelopmental disorders are prevalent, frequently occur in comorbidity and share substantial genetic correlation. Previous evidence has suggested a role for the ADGRL3 gene in Attention-Deficit/Hyperactivity Disorder (ADHD) susceptibility in several samples. Considering ADGRL3 functionality in central nervous system development and its previous association with neurodevelopmental disorders, we aimed to assess ADGRL3 influence in early-onset ADHD (before 7 years of age) and Autism Spectrum Disorder (ASD). The sample comprises 187 men diagnosed with early-onset ADHD, 135 boys diagnosed with ASD and 468 male blood donors. We tested the association of an ADGRL3 variant (rs6551665) with both early-onset ADHD and ASD susceptibility. We observed significant associations between ADGRL3-rs6551665 on ADHD and ASD susceptibilities; we found that G-carriers were at increased risk of ADHD and ASD, in accordance with previous studies. The overall evidence from the literature, corroborated by our results, suggests that ADGRL3 might be involved in brain development, and genetic modifications related to it might be part of a shared vulnerability factor associated with the underlying neurobiology of neurodevelopmental disorders such as ADHD and ASD.

Sequential Neuroimaging of the Fetus and Newborn With In Utero Zika Virus Exposure.

Importance: The evolution of fetal brain injury by Zika virus (ZIKV) infection is not well described. Objectives: To perform longitudinal neuroimaging of fetuses and infants exposed to in utero maternal ZIKV infection using concomitant magnetic resonance imaging (MRI) and ultrasonography (US), as well as to determine the duration of viremia in pregnant women with ZIKV infection and whether the duration of viremia correlated with fetal and/or infant brain abnormalities. Design, Setting, and Participants: A cohort of 82 pregnant women with clinical criteria for probable ZIKV infection in Barranquilla, Colombia, and Washington, DC, were enrolled from June 15, 2016, through June 27, 2017, with Colombian women identified by community recruitment and physician referral and travel-related cases of American women recruited from a Congenital Zika Program. Interventions and Exposures: Women received 1 or more MRI and US examinations during the second and/or third trimesters. Postnatally, infants underwent brain MRI and cranial US. Blood samples were tested for ZIKV. Main Outcomes and Measures: The neuroimaging studies were evaluated for brain injury and cerebral biometry. Results: Of the 82 women, 80 were from Colombia and 2 were from the United States. In 3 of 82 cases (4%), fetal MRI demonstrated abnormalities consistent with congenital ZIKV infection. Two cases had heterotopias and malformations in cortical development and 1 case had a parietal encephalocele, Chiari II malformation, and microcephaly. In 1 case, US results remained normal despite fetal abnormalities detected on MRI. Prolonged maternal polymerase chain reaction positivity was present in 1 case. Of the remaining 79 cases with normal results of prenatal imaging, postnatal brain MRI was acquired in 53 infants and demonstrated mild abnormalities in 7 (13%). Fifty-seven infants underwent postnatal cranial US, which detected changes of lenticulostriate vasculopathy, choroid plexus cysts, germinolytic/subependymal cysts, and/or calcification in 21 infants (37%). Conclusions and Relevance: In a cohort of pregnant women with ZIKV infection, prenatal US examination appeared to detect all but 1 abnormal fetal case. Postnatal neuroimaging in infants who had normal prenatal imaging revealed new mild abnormalities. For most patients, prenatal and postnatal US may identify ZIKV-related brain injury.

Maternal metabolic adaptations are necessary for normal offspring growth and brain development.

Several metabolic adaptations emerge during pregnancy and continue through lactation, including increases in food intake and body weight, as well as insulin and leptin resistance. These maternal adaptations are thought to play a role in offspring viability and success. Using a model of attenuated maternal metabolic adaptations induced by ablation of the Socs3 gene in leptin receptor expressing cells (SOCS3 KO mice), our study aimed to investigate whether maternal metabolic changes are required for normal offspring development, and if their absence causes metabolic imbalances in adulthood. The litters were subjected to a cross-fostering experimental design to distinguish the prenatal and postnatal effects caused by maternal metabolic adaptations. Males either born or raised by SOCS3 KO mice showed reduced body weight until 8 weeks of life. Both adult males and females born or raised by SOCS3 KO mice also had lower body adiposity. Despite that, no significant changes in energy expenditure, glucose tolerance or insulin resistance were observed. However, males either born or raised by SOCS3 KO mice showed reduced brain mass in adulthood. Furthermore, animals born from SOCS3 KO mice also had lower proopiomelanocortin fiber density in the paraventricular nucleus of the hypothalamus. In conclusion, these findings indicate that the commonly observed metabolic changes in pregnancy and lactation are necessary for normal offspring growth and brain development.