scholarly journals The Chemorepulsive Protein Semaphorin 3A and Perineuronal Net-Mediated Plasticity

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
F. de Winter ◽  
J. C. F. Kwok ◽  
J. W. Fawcett ◽  
T. T. Vo ◽  
D. Carulli ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Neuronal Plasticity ◽  
Adult Brain ◽  
Critical Periods ◽  
Inhibitory Effects ◽  
Perineuronal Net ◽  
Neuronal Populations ◽  
Biochemical Interaction ◽  
Chondroitin Sulfate E ◽  
The Brain

During postnatal development, closure of critical periods coincides with the appearance of extracellular matrix structures, called perineuronal nets (PNN), around various neuronal populations throughout the brain. The absence or presence of PNN strongly correlates with neuronal plasticity. It is not clear how PNN regulate plasticity. The repulsive axon guidance proteins Semaphorin (Sema) 3A and Sema3B are also prominently expressed in the postnatal and adult brain. In the neocortex, Sema3A accumulates in the PNN that form around parvalbumin positive inhibitory interneurons during the closure of critical periods. Sema3A interacts with high-affinity with chondroitin sulfate E, a component of PNN. The localization of Sema3A in PNN and its inhibitory effects on developing neurites are intriguing features and may clarify how PNN mediate structural neural plasticity. In the cerebellum, enhanced neuronal plasticity as a result of an enriched environment correlates with reduced Sema3A expression in PNN. Here, we first review the distribution of Sema3A and Sema3B expression in the rat brain and the biochemical interaction of Sema3A with PNN. Subsequently, we review what is known so far about functional correlates of changes in Sema3A expression in PNN. Finally, we propose a model of how Semaphorins in the PNN may influence local connectivity.

Neural Plasticity in Amblyopia

2021 ◽  
Author(s):  
Benjamin Thompson
Keyword(s):  
Visual Cortex ◽  
Neural Plasticity ◽  
Visual Information ◽  
Randomized Clinical Trials ◽  
Adult Brain ◽  
Abnormal Development ◽  
Sensitive Period ◽  
Early 21St Century ◽  
Functional Changes ◽  
The Brain

Early in life, the brain has a substantial capacity for change, often referred to as neuroplasticity. Disrupted visual input to the brain during an early “critical” or “sensitive period” of heightened neuroplasticity induces structural and functional changes within neural systems and causes amblyopia, a sensory disorder associated with abnormal development of the brain areas involved in perception. Amblyopia impairs a broad range of visual, multisensory, and motor functions, and recovery from amblyopia requires a substantial change in visual information processing within the brain. Therefore, not only is amblyopia caused by an interaction between visual experience and heightened neuroplasticity, recovery from amblyopia also requires significant neuroplastic change within the brain. A number of evidence-based treatments are available for young children with amblyopia whose brains are still rapidly developing and have a correspondingly high level of neuroplasticity. However, adults with amblyopia are often left untreated because of the idea that the adult brain no longer has sufficient neuroplasticity to relearn how to process visual information. In the early 21st century, it became clear that this idea was not correct. A number of interventions that can enhance neuroplasticity in the mature visual cortex have been identified using animal models of amblyopia and are now being translated into human studies. Other promising techniques for enhancing visual cortex neuroplasticity have emerged from studies of adult humans with amblyopia. Examples of interventions that may improve vision in adult amblyopia include refractive correction, patching of the amblyopic eye (reverse patching), monocular and binocular perceptual learning, noninvasive brain stimulation, systemic drugs, and exercise. The next important stage of research within this field will be to conduct fully controlled randomized clinical trials to assess which, if any, of these interventions can be translated into a mainstream treatment for amblyopia in adulthood.

scholarly journals Cholinergic System and NGF Receptors: Insights from the Brain of the Short-Lived Fish Nothobranchius furzeri

2020 ◽  
Vol 10 (6) ◽  
pp. 394
Author(s):  
Paolo de Girolamo ◽  
Adele Leggieri ◽  
Antonio Palladino ◽  
Carla Lucini ◽  
Chiara Attanasio ◽  
...  
Keyword(s):  
Cholinergic System ◽  
Preoptic Area ◽  
Cholinergic Neurons ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Neuronal Populations ◽  
Dependent Change ◽  
Nothobranchius Furzeri ◽  
Age Dependent ◽  
The Brain

Nerve growth factor (NGF) receptors are evolutionary conserved molecules, and in mammals are considered necessary for ensuring the survival of cholinergic neurons. The age-dependent regulation of NTRK1/NTRKA and p75/NGFR in mammalian brain results in a reduced response of the cholinergic neurons to neurotrophic factors and is thought to play a role in the pathogenesis of neurodegenerative diseases. Here, we study the age-dependent expression of NGF receptors (NTRK1/NTRKA and p75/NGFR) in the brain of the short-lived teleost fish Nothobranchius furzeri. We observed that NTRK1/NTRKA is more expressed than p75/NGFR in young and old animals, although both receptors do not show a significant age-dependent change. We then study the neuroanatomical organization of the cholinergic system, observing that cholinergic fibers project over the entire neuroaxis while cholinergic neurons appear restricted to few nuclei situated in the equivalent of mammalian subpallium, preoptic area and rostral reticular formation. Finally, our experiments do not confirm that NTRK1/NTRKA and p75/NGFR are expressed in cholinergic neuronal populations in the adult brain of N. furzeri. To our knowledge, this is the first study where NGF receptors have been analyzed in relation to the cholinergic system in a fish species along with their age-dependent modulation. We observed differences between mammals and fish, which make the African turquoise killifish an attractive model to further investigate the fish specific NGF receptors regulation.

scholarly journals Early life nutrition and neural plasticity

2015 ◽  
Vol 27 (2) ◽  
pp. 411-423 ◽  
Author(s):  
Michael K. Georgieff ◽  
Katya E. Brunette ◽  
Phu V. Tran
Keyword(s):  
Neural Plasticity ◽  
Environmental Exposures ◽  
Brain Regions ◽  
Adult Brain ◽  
Fetal Life ◽  
Biological Mechanisms ◽  
The Individual ◽  
Opening And Closing ◽  
The Brain ◽  
Developmental Maturation

AbstractThe human brain undergoes a remarkable transformation during fetal life and the first postnatal years from a relatively undifferentiated but pluripotent organ to a highly specified and organized one. The outcome of this developmental maturation is highly dependent on a sequence of environmental exposures that can have either positive or negative influences on the ultimate plasticity of the adult brain. Many environmental exposures are beyond the control of the individual, but nutrition is not. An ever-increasing amount of research demonstrates not only that nutrition shapes the brain and affects its function during development but also that several nutrients early in life have profound and long-lasting effects on the brain. Nutrients have been shown to alter opening and closing of critical and sensitive periods of particular brain regions. This paper discusses the roles that various nutrients play in shaping the developing brain, concentrating specifically on recently explicated biological mechanisms by which particularly salient nutrients influence childhood and adult neural plasticity.

scholarly journals An Extracellular Perspective on CNS Maturation: Perineuronal Nets and the Control of Plasticity

2021 ◽  
Vol 22 (5) ◽  
pp. 2434
Author(s):  
Daniela Carulli ◽  
Joost Verhaagen
Keyword(s):  
Critical Period ◽  
Brain Plasticity ◽  
Time Windows ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Postnatal Life ◽  
Perineuronal Nets ◽  
Critical Periods ◽  
Perineuronal Net ◽  
Memory Processes

During restricted time windows of postnatal life, called critical periods, neural circuits are highly plastic and are shaped by environmental stimuli. In several mammalian brain areas, from the cerebral cortex to the hippocampus and amygdala, the closure of the critical period is dependent on the formation of perineuronal nets. Perineuronal nets are a condensed form of an extracellular matrix, which surrounds the soma and proximal dendrites of subsets of neurons, enwrapping synaptic terminals. Experimentally disrupting perineuronal nets in adult animals induces the reactivation of critical period plasticity, pointing to a role of the perineuronal net as a molecular brake on plasticity as the critical period closes. Interestingly, in the adult brain, the expression of perineuronal nets is remarkably dynamic, changing its plasticity-associated conditions, including memory processes. In this review, we aimed to address how perineuronal nets contribute to the maturation of brain circuits and the regulation of adult brain plasticity and memory processes in physiological and pathological conditions.

scholarly journals Chondroitin 6-Sulfation Regulates Perineuronal Net Formation by Controlling the Stability of Aggrecan

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Shinji Miyata ◽  
Hiroshi Kitagawa
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulfate ◽  
Neural Plasticity ◽  
Adult Brain ◽  
Chondroitin Sulfate Proteoglycans ◽  
Perineuronal Nets ◽  
Perineuronal Net ◽  
A Disintegrin And Metalloproteinase ◽  
The Stability ◽  
Thrombospondin Motif

Perineuronal nets (PNNs) are lattice-like extracellular matrix structures composed of chondroitin sulfate proteoglycans (CSPGs). The appearance of PNNs parallels the decline of neural plasticity, and disruption of PNNs reactivates neural plasticity in the adult brain. We previously reported that sulfation patterns of chondroitin sulfate (CS) chains on CSPGs influenced the formation of PNNs and neural plasticity. However, the mechanism of PNN formation regulated by CS sulfation remains unknown. Here we found that overexpression of chondroitin 6-sulfotransferase-1 (C6ST-1), which catalyzes 6-sulfation of CS chains, selectively decreased aggrecan, a major CSPG in PNNs, in the aged brain without affecting other PNN components. Both diffuse and PNN-associated aggrecans were reduced by overexpression of C6ST-1. C6ST-1 increased 6-sulfation in both the repeating disaccharide region and linkage region of CS chains. Overexpression of 6-sulfation primarily impaired accumulation of aggrecan in PNNs, whereas condensation of other PNN components was not affected. Finally, we found that increased 6-sulfation accelerated proteolysis of aggrecan by a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS) protease. Taken together, our results indicate that sulfation patterns of CS chains on aggrecan influenced the stability of the CSPG, thereby regulating formation of PNNs and neural plasticity.

scholarly journals An architectonic type principle in the development of laminar patterns of cortico-cortical connections

2021 ◽  
Author(s):  
Sarah F. Beul ◽  
Alexandros Goulas ◽  
Claus C. Hilgetag
Keyword(s):  
Structural Connectivity ◽  
Macaque Monkey ◽  
Brain Regions ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Cortical Connections ◽  
Cortical Projections ◽  
Structural Connections ◽  
High Degree ◽  
The Brain

AbstractStructural connections between cortical areas form an intricate network with a high degree of specificity. Many aspects of this complex network organization in the adult mammalian cortex are captured by an architectonic type principle, which relates structural connections to the architectonic differentiation of brain regions. In particular, the laminar patterns of projection origins are a prominent feature of structural connections that varies in a graded manner with the relative architectonic differentiation of connected areas in the adult brain. Here we show that the architectonic type principle is already apparent for the laminar origins of cortico-cortical projections in the immature cortex of the macaque monkey. We find that prenatal and neonatal laminar patterns correlate with cortical architectonic differentiation, and that the relation of laminar patterns to architectonic differences between connected areas is not substantially altered by the complete loss of visual input. Moreover, we find that the degree of change in laminar patterns that projections undergo during development varies in proportion to the relative architectonic differentiation of the connected areas. Hence, it appears that initial biases in laminar projection patterns become progressively strengthened by later developmental processes. These findings suggest that early neurogenetic processes during the formation of the brain are sufficient to establish the characteristic laminar projection patterns. This conclusion is in line with previously suggested mechanistic explanations underlying the emergence of the architectonic type principle and provides further constraints for exploring the fundamental factors that shape structural connectivity in the mammalian brain.

scholarly journals Transfer of rhodamine-123 into the brain and cerebrospinal fluid of fetal, neonatal and adult rats

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Liam M. Koehn ◽  
Katarzyna M. Dziegielewska ◽  
Mark D. Habgood ◽  
Yifan Huang ◽  
Norman R. Saunders
Keyword(s):  
Cerebrospinal Fluid ◽  
Fetal Brain ◽  
Maternal Blood ◽  
Adult Brain ◽  
Rhodamine 123 ◽  
Patient Specific ◽  
Adult Rats ◽  
Blood Brain ◽  
The Brain ◽  
Brain Barriers

Abstract Background Adenosine triphosphate binding cassette transporters such as P-glycoprotein (PGP) play an important role in drug pharmacokinetics by actively effluxing their substrates at barrier interfaces, including the blood-brain, blood-cerebrospinal fluid (CSF) and placental barriers. For a molecule to access the brain during fetal stages it must bypass efflux transporters at both the placental barrier and brain barriers themselves. Following birth, placental protection is no longer present and brain barriers remain the major line of defense. Understanding developmental differences that exist in the transfer of PGP substrates into the brain is important for ensuring that medication regimes are safe and appropriate for all patients. Methods In the present study PGP substrate rhodamine-123 (R123) was injected intraperitoneally into E19 dams, postnatal (P4, P14) and adult rats. Naturally fluorescent properties of R123 were utilized to measure its concentration in blood-plasma, CSF and brain by spectrofluorimetry (Clariostar). Statistical differences in R123 transfer (concentration ratios between tissue and plasma ratios) were determined using Kruskal-Wallis tests with Dunn’s corrections. Results Following maternal injection the transfer of R123 across the E19 placenta from maternal blood to fetal blood was around 20 %. Of the R123 that reached fetal circulation 43 % transferred into brain and 38 % into CSF. The transfer of R123 from blood to brain and CSF was lower in postnatal pups and decreased with age (brain: 43 % at P4, 22 % at P14 and 9 % in adults; CSF: 8 % at P4, 8 % at P14 and 1 % in adults). Transfer from maternal blood across placental and brain barriers into fetal brain was approximately 9 %, similar to the transfer across adult blood-brain barriers (also 9 %). Following birth when placental protection was no longer present, transfer of R123 from blood into the newborn brain was significantly higher than into adult brain (3 fold, p < 0.05). Conclusions Administration of a PGP substrate to infant rats resulted in a higher transfer into the brain than equivalent doses at later stages of life or equivalent maternal doses during gestation. Toxicological testing of PGP substrate drugs should consider the possibility of these patient specific differences in safety analysis.

Mesencephalic GABA neuronal development: no more on the other side of oblivion

2014 ◽  
Vol 5 (5) ◽  
pp. 371-382 ◽  
Author(s):  
Suyan Li ◽  
Sampada Joshee ◽  
Anju Vasudevan
Keyword(s):  
Transcriptional Control ◽  
Neuronal Development ◽  
Developmental Regulation ◽  
Molecular Characteristics ◽  
Psychiatric Illnesses ◽  
Neuronal Populations ◽  
Gaba Neurons ◽  
Recent Developments ◽  
And Function ◽  
The Brain

AbstractMidbrain GABA neurons, endowed with multiple morphological, physiological and molecular characteristics as well as projection patterns are key players interacting with diverse regions of the brain and capable of modulating several aspects of behavior. The diversity of these GABA neuronal populations based on their location and function in the dorsal, medial or ventral midbrain has challenged efforts to rapidly uncover their developmental regulation. Here we review recent developments that are beginning to illuminate transcriptional control of GABA neurons in the embryonic midbrain (mesencephalon) and discuss its implications for understanding and treatment of neurological and psychiatric illnesses.

scholarly journals Programming of the reproductive axis by hormonal and genetic manipulation in mice

Reproduction ◽  
2018 ◽  
Author(s):  
Susana B Rulli ◽  
María Julia Cambiasso ◽  
Laura D Ratner
Keyword(s):  
Sex Chromosome ◽  
Genetic Manipulation ◽  
Sex Differentiation ◽  
Reproductive Function ◽  
Gonadal Steroids ◽  
Critical Periods ◽  
Female Reproduction ◽  
Control Male ◽  
Male And Female ◽  
The Brain

In mammals, the reproductive function is controlled by the hypothalamic-pituitary-gonadal axis. During development, mechanisms mediated by gonadal steroids exert an imprinting at the hypothalamic-pituitary level, by establishing sexual differences in the circuits that control male and female reproduction. In rodents, the testicular production of androgens increases drastically during the fetal/neonatal stage. This process is essential for the masculinization of the reproductive tract, genitals and brain. The conversion of androgens to estrogens in the brain is crucial for the male sexual differentiation and behavior. Conversely, feminization of the brain occurs in the absence of high levels of gonadal steroids during the perinatal period in females. Potential genetic contribution to the differentiation of brain cells through direct effects of genes located on sex chromosomes is also relevant. In this review, we will focus on the phenotypic alterations that occur on the hypothalamic-pituitary-gonadal axis of transgenic mice with persistently elevated expression of the human chorionic gonadotropin hormone (hCG). Excess of endogenously synthesized gonadal steroids due to a constant hCG stimulation is able to disrupt the developmental programming of the hypothalamic-pituitary axis in both transgenic males and females. Locally produced estrogens by the hypothalamic aromatase might play a key role in the phenotype of these mice. The “four core genotypes” mouse model demonstrated a potential influence of sex chromosome genes in brain masculinization before critical periods of sex differentiation. Thus, hormonal and genetic factors interact to regulate the local production of the neurosteroids necessary for the programming of the male and female reproductive function.

The novel guanylyl cyclase MsGC-I is strongly expressed in higher-order neuropils in the brain of Manduca sexta

2001 ◽  
Vol 204 (2) ◽  
pp. 305-314 ◽  
Author(s):  
A. Nighorn ◽  
P.J. Simpson ◽  
D.B. Morton
Keyword(s):  
Nervous System ◽  
Manduca Sexta ◽  
Guanylyl Cyclase ◽  
Higher Order ◽  
Adult Brain ◽  
Central Complex ◽  
Amino Acid Residues ◽  
Order Processing ◽  
Guanylyl Cyclases ◽  
The Brain

Guanylyl cyclases are usually characterized as being either soluble (sGCs) or receptor (rGCs). We have recently cloned a novel guanylyl cyclase, MsGC-I, from the developing nervous system of the hawkmoth Manduca sexta that cannot be classified as either an sGC or an rGC. MsGC-I shows highest sequence identity with receptor guanylyl cyclases throughout its catalytic and dimerization domains, but does not contain the ligand-binding, transmembrane or kinase-like domains characteristic of receptor guanylyl cyclases. In addition, MsGC-I contains a C-terminal extension of 149 amino acid residues. In this paper, we report the expression of MsGC-I in the adult. Northern blots show that it is expressed preferentially in the nervous system, with high levels in the pharate adult brain and antennae. In the antennae, immunohistochemical analyses show that it is expressed in the cell bodies and dendrites, but not axons, of olfactory receptor neurons. In the brain, it is expressed in a variety of sensory neuropils including the antennal and optic lobes. It is also expressed in structures involved in higher-order processing including the mushroom bodies and central complex. This complicated expression pattern suggests that this novel guanylyl cyclase plays an important role in mediating cyclic GMP levels in the nervous system of Manduca sexta.

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