Evolution Of Central Nervous System Research Articles

Capitella teleta gets left out: possible evolutionary shift causes loss of left tissues rather than increased neural tissue from dominant-negative BMPR1

BackgroundThe evolution of central nervous systems (CNSs) is a fascinating and complex topic; further work is needed to understand the genetic and developmental homology between organisms with a CNS. Research into a limited number of species suggests that CNSs may be homologous across Bilateria. This hypothesis is based in part on similar functions of BMP signaling in establishing fates along the dorsal-ventral (D-V) axis, including limiting neural specification to one ectodermal region. From an evolutionary-developmental perspective, the best way to understand a system is to explore it in a wide range of organisms to create a full picture.MethodsHere, we expand our understanding of BMP signaling in Spiralia, the third major clade of bilaterians, by examining phenotypes after expression of a dominant-negative BMP Receptor 1 and after knock-down of the putative BMP antagonist Chordin-like using CRISPR/Cas9 gene editing in the annelid Capitella teleta (Pleistoannelida).ResultsEctopic expression of the dominant-negative Ct-BMPR1 did not increase CNS tissue or alter overall D-V axis formation in the trunk. Instead, we observed a unique asymmetrical phenotype: a distinct loss of left tissues, including the left eye, brain, foregut, and trunk mesoderm. Adding ectopic BMP4 early during cleavage stages reversed the dominant-negative Ct-BMPR1 phenotype, leading to a similar loss or reduction of right tissues instead. Surprisingly, a similar asymmetrical loss of left tissues was evident from CRISPR knock-down of Ct-Chordin-like but concentrated in the trunk rather than the episphere.ConclusionsOur data highlight a novel asymmetrical phenotype, giving us further insight into the complicated story of BMP’s developmental role. We further solidify the hypothesis that the function of BMP signaling during the establishment of the D-V axis and CNS is fundamentally different in at least Pleistoannelida, possibly in Spiralia, and is not required for nervous system delimitation in this group.

Phagocytic microglia and macrophages in brain injury and repair.

AimsPhagocytosis is the cellular digestion of extracellular particles, such as pathogens and dying cells, and is a key element in the evolution of central nervous system (CNS) disorders. Microglia and macrophages are the professional phagocytes of the CNS. By clearing toxic cellular debris and reshaping the extracellular matrix, microglia/macrophages help pilot the brain repair and functional recovery process. However, CNS resident and invading immune cells can also magnify tissue damage by igniting runaway inflammation and phagocytosing stressed—but viable—neurons.DiscussionMicroglia/macrophages help mediate intercellular communication and react quickly to the “find‐me” signals expressed by dead/dying neurons. The activated microglia/macrophages then migrate to the injury site to initiate the phagocytic process upon encountering “eat‐me” signals on the surfaces of endangered cells. Thus, healthy cells attempt to avoid inappropriate engulfment by expressing “do not‐eat‐me” signals. Microglia/macrophages also have the capacity to phagocytose immune cells that invade the injured brain (e.g., neutrophils) and to regulate their pro‐inflammatory properties. During brain recovery, microglia/macrophages engulf myelin debris, initiate synaptogenesis and neurogenesis, and sculpt a favorable extracellular matrix to support network rewiring, among other favorable roles. Here, we review the multilayered nature of phagocytotic microglia/macrophages, including the molecular and cellular mechanisms that govern microglia/macrophage‐induced phagocytosis in acute brain injury, and discuss strategies that tap into the therapeutic potential of this engulfment process.ConclusionIdentification of biological targets that can temper neuroinflammation after brain injury without hindering the essential phagocytic functions of microglia/macrophages will expedite better medical management of the stroke recovery stage.

Compartmentalization of cerebrospinal fluid inflammation across the spectrum of untreated HIV-1 infection, central nervous system injury and viral suppression.

ObjectiveTo characterize the evolution of central nervous system (CNS) inflammation in HIV-1 infection applying a panel of cerebrospinal fluid (CSF) inflammatory biomarkers to grouped subjects representing a broad spectrum of systemic HIV-1 immune suppression, CNS injury and viral control.MethodsThis is a cross-sectional analysis of archived CSF and blood samples, assessing concentrations of 10 functionally diverse soluble inflammatory biomarkers by immunoassays in 143 HIV-1-infected subjects divided into 8 groups: untreated primary HIV-1 infection (PHI); four untreated groups defined by their blood CD4+ T lymphocyte counts; untreated patients presenting with subacute HIV-associated dementia (HAD); antiretroviral-treated subjects with ≥1 years of plasma viral suppression; and untreated elite controllers. Twenty HIV-1-uninfected controls were included for comparison. Background biomarkers included blood CD4+ and CD8+ T lymphocytes, CSF and blood HIV-1 RNA, CSF white blood cell (WBC) count, CSF/blood albumin ratio, CSF neurofilament light chain (NfL), and CSF t-tau.FindingsHIV-1 infection was associated with a broad compartmentalized CSF inflammatory response that developed early in its course and changed with systemic disease progression, development of neurological injury, and viral suppression. CSF inflammation in untreated individuals without overt HAD exhibited at least two overall patterns of inflammation as blood CD4+ T lymphocytes decreased: one that peaked at 200–350 blood CD4+ T cells/μL and associated with lymphocytic CSF inflammation and HIV-1 RNA concentrations; and a second that steadily increased through the full range of CD4+ T cell decline and associated with macrophage responses and increasing CNS injury. Subacute HAD was distinguished by a third inflammatory profile with increased blood-brain barrier permeability and robust combined lymphocytic and macrophage CSF inflammation. Suppression of CSF and blood HIV-1 infections by antiretroviral treatment and elite viral control were associated with reduced CSF inflammation, though not fully to levels found in HIV-1 seronegative controls.

Magnetic resonance diffusion tensor tractography of a midbrain auditory circuit in Alligator

Knowledge of brain circuitry is critical for understanding the organization, function, and evolution of central nervous systems. Most commonly, brain connections have been elucidated using histological and experimental methods that require animal sacrifice. On the other hand, magnetic resonance diffusion tensor imaging and associated tractography have emerged as a preferred method to noninvasively visualize brain white matter tracts. However, existing studies have primarily examined large, heavily myelinated fiber tracts. Whether tractography can visualize fiber bundles that contain thin and poorly myelinated axons is uncertain. To address this question, the midbrain auditory pathway to the thalamus was investigated in Alligator. This species was chosen because of its evolutionary importance as it is the reptilian group most closely related to birds and because its brain contains many thin and poorly myelinated tracts. Furthermore, this auditory pathway is well documented in other reptiles, including a related crocodilian. Histological observations and experimental determination of anterograde connections confirmed this path in Alligator. Tractography identified these tracts in Alligator and provided a 3-dimensional picture that accurately identified the neural elements of this circuit. In addition, tractography identified one possible unrecognized pathway. These results demonstrate that tractography can visualize circuits containing thin, poorly myelinated fibers. These findings open the door for future studies to examine these types of pathways in other vertebrates.

The evolution of central nervous system prophylaxis for patients with acute lymphoblastic leukemia.

The evolution of central nervous system prophylaxis for patients with acute lymphoblastic leukemia.

Evidence for the coevolution of axon guidance molecule Netrin and its receptor Frazzled.

Coevolution of a ligand and its receptor is critical for maintaining their function in different species, but how ligand and its receptor coevolve is poorly understood. The axon guidance molecule Netrin and its receptor Frazzled (Fra) are useful to study the mechanisms of ligand-receptor coevolution. Here, we have applied codon substitution models to identify positive selection of the netrin and fra genes. The sites under positive selection in netrin and fra were detected in same lineage, such as nematode, dipteran, hymenopteran, hemichordate, and teleost. Several amino acid residues that are under positive selection were identified in the interaction domains. Here we provide evidence that positive selection is essential for the coevolution of Netrin and Fra during central nervous system evolution.

Evolution of vertebrate central nervous system is accompanied by novel expression changes of duplicate genes

The evolution of the central nervous system (CNS) is one of the most striking changes during the transition from invertebrates to vertebrates. As a major source of genetic novelties, gene duplication might play an important role in the functional innovation of vertebrate CNS. In this study, we focused on a group of CNS-biased genes that duplicated during early vertebrate evolution. We investigated the tempo-spatial expression patterns of 33 duplicate gene families and their orthologs during the embryonic development of the vertebrate Xenopus laevis and the cephalochordate Brachiostoma belcheri. Almost all the identified duplicate genes are differentially expressed in the CNS in Xenopus embryos, and more than 50% and 30% duplicate genes are expressed in the telencephalon and mid-hindbrain boundary, respectively, which are mostly considered as two innovations in the vertebrate CNS. Interestingly, more than 50% of the amphioxus orthologs do not show apparent expression in the CNS in amphioxus embryos as detected by in situ hybridization, indicating that some of the vertebrate CNS-biased duplicate genes might arise from non-CNS genes in invertebrates. Our data accentuate the functional contribution of gene duplication in the CNS evolution of vertebrate and uncover an invertebrate non-CNS history for some vertebrate CNS-biased duplicate genes.

Assessing atrophy of the major white matter fiber bundles of the brain from diffusion tensor MRI data

Brain atrophy is a typical feature of many neurological conditions. Therefore, quantitative evaluation and spatial characterization of atrophy are potentially useful for monitoring the evolution of central nervous system (CNS) disorders. In this study, a method for measuring atrophy of the major white matter (WM) fiber bundles in the brain using diffusion tensor (DT) MRI data is developed. To this end, an atlas was created from sets of diffusion anisotropy images from normal subjects, and the deformations necessary to match single subject anisotropy images to this atlas were then computed. Because diffusion anisotropy images were used, this approach should be sensitive to fiber bundle volume changes in the same way that using T1-weighted images allows gray matter volume changes to be measured. The Jacobian determinant of the deformation field for each subject was then used as a measure of contraction or expansion of the tissue at each image voxel. An overview of the nonlinear registration problem is given; then an optimization of the parameters for the chosen algorithm is performed and the method for producing the atlas is described. The effectiveness of the method was then tested on data from five patients with multiple sclerosis (MS) and two patients with amyotrophic lateral sclerosis (ALS).

Hox gene expression in the hemichordate Saccoglossus kowalevskii and the evolution of deuterostome nervous systems

The evolutionary origins of the chordate central nervous system remain uncertain. Conclusions drawn from classical morphological comparisons and from a broad range of metazoan phyla conflict with the new molecular genetic information from developmental model systems characterized by central nervous systems. This has led to debate as to the nature of the ancestral deuterostome nervous system. Hemichordates as basal deuterostomes occupy a phylogenetically critical position for addressing hypotheses on the evolution of the chordate nervous system. Characterizing the molecular basis of the development of their diffuse nervous system offers insights into the role of conserved body patterning genes in the evolution of specific neural anatomies. We present a description of hox gene expression during the development of the direct-developing hemichordate Saccoglossus kowalevskii. The nested ectodermal expression of these genes in a hemichordate suggest that they play a general patterning role in the anterior/posterior regionalization of the ectoderm of bilaterians rather than being uniquely associated with the development and evolution of central nervous systems.

A prospective four-year follow-up of neuropsychological function in HIV seropositive and seronegative methadone-maintained patients

The evolution of central nervous system (CNS) impairments associated with human immunodeficiency virus (HIV) infection was assessed by a prospective, longitudinal study of patients in a methadone maintenance clinic. At a mean of 47 months after baseline testing, which included physical exams, HIV antibody testing and a neuropsychological (NP) screening battery, 121 subjects received a second NP assessment. Forty subjects (33%) who were seropositive at baseline showed statistically significant declines in NP function over the 4 years compared with 81 seronegatives, on the Finger Tapping and Trail Making B tests. This relatively long-term follow-up suggests that subtle cognitive deficits develop over time and can be identified early, but their course is slow and appears generally to parallel that of non-CNS symptoms/signs of HIV infection.

P 050 Magnetic resonance (MR) evolution of central nervous system (CNS) lesions in patients with Behçet's disease (BD)

P 050 Magnetic resonance (MR) evolution of central nervous system (CNS) lesions in patients with Behçet's disease (BD)

On the evolution of central nervous systems: Implications from polyclad turbellarian neurobiology

The nervous system of the polyclad turbellarian Notoplana acticola consists of a series of nerve plexuses and a central ganglion, the brain. The brain contains a variety of cell types including multipolar heteropolar and bipolar neurons. These cell types are rare in other invertebrate ganglia. Individual neurons also contain a variety of different ion channels. both spiking and nonspiking neurons are found. Some neurons are multimodal interneurons. Habituation appears to be a postsynaptic phenomenon. Sensitization and long-term potentiation have not been demonstrated. Polyclads appear to represent a stage in the evolution of centralized nervous systems where much of the neuronal machinery underlying behavior occurs in the peripheral nervous system and the brain's main functions are the coordination and sequencing of peripherally placed reflexes. Even at this stage, however, the brain already contains cells that seem as advanced as those found in higher organisms.