The microbiota and the gut-brain axis: insights from the temporal and spatial mucosal alterations during colonisation of the germfree mouse intestine

2012 ◽  
Vol 3 (4) ◽  
pp. 251-259 ◽  
Author(s):  
S. El Aidy ◽  
W. Kunze ◽  
J. Bienenstock ◽  
M. Kleerebezem
Keyword(s):  
Nervous System ◽  
Neuronal Development ◽  
Neuronal Response ◽  
Time Resolved ◽  
Altered Expression ◽  
Germfree Mouse ◽  
Plasma Tryptophan ◽  
Expression Of Genes ◽  
Mouse Intestine ◽  
And Function

The influence of the gut microbiota on the nervous system, brain development and behaviour, in particular during microbial colonisation of the host, has recently been receiving profound interest. Our time-resolved mining of combined data analyses of the ex-germfree mouse intestine during a 30-day course of colonisation with conventional mouse faecal microbiota (conventionalisation), shed light on temporal altered expression of genes of which the products influenced functions of the nervous system. Plasma tryptophan and kynurenine levels reflected high indoleamine dioxygenase activity, which was supported by significant temporal induction of the encoding gene in all gut tissues. However, the majority of genes associated with neuronal development and function were reduced. Colonic substance P elevation in response to conventionalisation was higher only after 30-days. These results support a functional microbiota-neurohumoral relationship during conventionalisation and suggest a delayed neuronal response that is elicited only after the microbiota accommodating homeostasis has been accomplished.

scholarly journals The Amyloid Precursor-like Protein APL-1 Regulates Axon Regeneration

2018 ◽  
Author(s):  
Lewie Zeng ◽  
Rachid El Bejjani ◽  
Marc Hammarlund
Keyword(s):  
Motor Neurons ◽  
Neuronal Development ◽  
Axon Regeneration ◽  
Neuronal Response ◽  
Small Gtpase ◽  
C Elegans ◽  
Protein Levels ◽  
Mature Neurons ◽  
And Function

AbstractMembers of the Amyloid Precursor Protein (APP) family have important functions during neuronal development. However, their physiological functions in the mature nervous system are not fully understood. Here we use the C. elegans GABAergic motor neurons to study the post-developmental function of the APP-like protein APL-1 in vivo. We find that apl-1 has minimum roles in the maintenance of gross neuron morphology and function. However, we show that apl-1 is an inhibitor of axon regeneration, acting on mature neurons to limit regrowth in response to injury. The small GTPase Rab6/RAB-6.2 also inhibits regeneration, and does so in part by maintaining protein levels of APL-1. To inhibit regeneration, APL-1 functions via the E2 domain of its ectodomain; the cytoplasmic tail, transmembrane anchoring, and the E1 domain are not required for this function. Our data defines a novel role for APL-1 in modulating the neuronal response to injury.

scholarly journals Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice

2019 ◽  
Vol 20 (14) ◽  
pp. 3543 ◽  
Author(s):  
Francisco Alén ◽  
Isabel Gómez-Redondo ◽  
Patricia Rivera ◽  
Juan Suárez ◽  
Priscila Ramos-Ibeas ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Intron Retention ◽  
Mutant Mice ◽  
Behavioral Alterations ◽  
Altered Expression ◽  
Cell Network ◽  
Expression Of Genes ◽  
Adult Cell ◽  
Controlling Behavior ◽  
And Function

Mutant mice with respect to the splicing factor Zrsr1 present altered spermatogenesis and infertility. To investigate whether Zrsr1 is involved in the homeostatic control that the hypothalamus exerts over reproductive functions, we first analyzed both differential gene and isoform expression and alternative splicing alterations in Zrsr1 mutant (Zrsr1mu) hypothalamus; second, we analyzed the spontaneous and social behavior of Zrsr1mu mice; and third, we analyzed adult cell proliferation and survival in the Zrsr1mu hypothalamus. The Zrsr1mu hypothalamus showed altered expression of genes and isoforms related to the glutathione metabolic process, synaptonemal complex assembly, mRNA transport, and altered splicing events involving the enrichment of U12-type intron retention (IR). Furthermore, increased IR in U12-containing genes related with the prolactin, progesterone, and gonadotropin-releasing hormone (GnRH) reproductive signaling pathway was observed. This was associated with a hyperactive phenotype in both males and females, with an anxious phenotype in females, and with increased social interaction in males, instead of the classical aggressive behavior. In addition, Zrsr1mu females but not males exhibited reduced cell proliferation in both the hypothalamus and the subventricular zone. Overall, these results suggest that Zrsr1 expression and function are relevant to organization of the hypothalamic cell network controlling behavior.

Development of cranial parasympathetic ganglia requires sequential actions of GDNF and neurturin

Development ◽  
2000 ◽  
Vol 127 (22) ◽  
pp. 4877-4889
Author(s):  
H. Enomoto ◽  
R.O. Heuckeroth ◽  
J.P. Golden ◽  
E.M. Johnson ◽  
J. Milbrandt
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Neurotrophic Factors ◽  
Altered Expression ◽  
Parasympathetic Ganglia ◽  
Neuronal Precursors ◽  
Parasympathetic Ganglion ◽  
And Function ◽  
Further Development ◽  
Predominant Expression

The neurotrophic factors that influence the development and function of the parasympathetic branch of the autonomic nervous system are obscure. Recently, neurturin has been found to provide trophic support to neurons of the cranial parasympathetic ganglion. Here we show that GDNF signaling via the RET/GFR(alpha)1 complex is crucial for the development of cranial parasympathetic ganglia including the submandibular, sphenopalatine and otic ganglia. GDNF is required early for proliferation and/or migration of the neuronal precursors for the sphenopalatine and otic ganglia. Neurturin exerts its effect later and is required for further development and maintenance of these neurons. This switch in ligand dependency during development is at least partly governed by the altered expression of GFR(α) receptors, as evidenced by the predominant expression of GFR(α)2 in these neurons after ganglion formation.

scholarly journals Impact of maternal malnutrition on gut barrier defence: implications for pregnancy health and fetal development.

2019 ◽  
Author(s):  
Sebastian A. Srugo ◽  
Enrrico Bloise ◽  
Tina Tu-Thu Ngoc Nguyen ◽  
Kristin L. Connor
Keyword(s):  
Mrna Expression ◽  
Control Diet ◽  
Paneth Cell ◽  
Goblet Cells ◽  
Maternal Malnutrition ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Enteric Glial Cells ◽  
Host Microbe Interactions ◽  
And Function

Small intestinal Paneth cells, enteric glial cells (EGC), and goblet cells maintain gut mucosal integrity, homeostasis, and influence host physiology locally and through the gut-brain axis. Little is known about their roles during pregnancy, or how maternal malnutrition impacts these cells and their development. Pregnant mice were fed a control diet (CON), undernourished by 30% vs. control (UN), or fed a high-fat diet (HF). At day 18.5 (term=19), gut integrity and function were assessed by immunohistochemistry and qPCR. UN mothers displayed reduced mRNA expression of Paneth cell antimicrobial peptides (AMP; Lyz2, Reg3g) and an accumulation of villi goblet cells, while HF had reduced Reg3g and mucin (Muc2) mRNA and increased lysozyme protein. UN fetuses had increased mRNA expression of gut transcription factor Sox9, associated with reduced expression of maturation markers (Cdx2, Muc2), and increased expression of tight junctions (TJ; Cldn-7). HF fetuses had increased mRNA expression of EGC markers (S100b, Bfabp, Plp1), AMP (Lyz1, Defa1, Reg3g), and TJ (Cldn-3, Cldn-7), and reduced expression of an AMP-activator (Tlr4). Maternal malnutrition altered expression of genes that maintain maternal gut homeostasis, and altered fetal gut permeability, function, and development. This may have long-term implications for host-microbe interactions, immunity, and offspring gut-brain axis function.

scholarly journals Exploring the Regulatory Role of Circular RNAs in Neurodegenerative Disorders

2019 ◽  
Vol 20 (21) ◽  
pp. 5477 ◽  
Author(s):  
Eleonora D’Ambra ◽  
Davide Capauto ◽  
Mariangela Morlando
Keyword(s):  
Nervous System ◽  
Neuronal Development ◽  
Circular Rnas ◽  
Pathological Conditions ◽  
Exact Function ◽  
Modulation Of Gene Expression ◽  
Development And Aging ◽  
And Function ◽  
Regulatory Functions

Circular RNAs (circRNAs) are a distinctive class of regulatory non-coding RNAs characterised by the presence of covalently closed ends. They are evolutionary conserved molecules, and although detected in different tissues, circRNAs resulted specifically enriched in the nervous system. Recent studies have shown that circRNAs are dynamically modulated during neuronal development and aging, that circRNAs are enriched at synaptic levels and resulted modulated after synaptic plasticity induction. This has suggested that circRNAs might play an important role in neuronal specification and activity. Despite the exact function of circRNAs is still poorly understood, emerging evidence indicates that circRNAs have important regulatory functions that might extensively contribute to the dynamic modulation of gene expression that supports neuronal pathways. More interestingly, deregulation of circRNAs expression has been linked with various pathological conditions. In this review, we describe current advances in the field of circRNA biogenesis and function in the nervous system both in physiological and in pathological conditions, and we specifically lay out their association with neurodegenerative diseases. Furthermore, we discuss the opportunity to exploit circRNAs for innovative therapeutic approaches and, due to their high stability, to use circRNAs as suitable biomarkers for diagnosis and disease progression.

scholarly journals Impact of Maternal Malnutrition on Gut Barrier Defense: Implications for Pregnancy Health and Fetal Development

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1375 ◽  
Author(s):  
Sebastian A. Srugo ◽  
Enrrico Bloise ◽  
Tina Tu-Thu Ngoc Nguyen ◽  
Kristin L. Connor
Keyword(s):  
Mrna Expression ◽  
Control Diet ◽  
Paneth Cell ◽  
Goblet Cells ◽  
Maternal Malnutrition ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Enteric Glial Cells ◽  
Host Microbe Interactions ◽  
And Function

Small intestinal Paneth cells, enteric glial cells (EGC), and goblet cells maintain gut mucosal integrity, homeostasis, and influence host physiology locally and through the gut-brain axis. Little is known about their roles during pregnancy, or how maternal malnutrition impacts these cells and their development. Pregnant mice were fed a control diet (CON), undernourished by 30% vs. control (UN), or fed a high fat diet (HF). At day 18.5 (term = 19), gut integrity and function were assessed by immunohistochemistry and qPCR. UN mothers displayed reduced mRNA expression of Paneth cell antimicrobial peptides (AMP; Lyz2, Reg3g) and an accumulation of villi goblet cells, while HF had reduced Reg3g and mucin (Muc2) mRNA and increased lysozyme protein. UN fetuses had increased mRNA expression of gut transcription factor Sox9, associated with reduced expression of maturation markers (Cdx2, Muc2), and increased expression of tight junctions (TJ; Cldn-7). HF fetuses had increased mRNA expression of EGC markers (S100b, Bfabp, Plp1), AMP (Lyz1, Defa1, Reg3g), and TJ (Cldn-3, Cldn-7), and reduced expression of an AMP-activator (Tlr4). Maternal malnutrition altered expression of genes that maintain maternal gut homeostasis, and altered fetal gut permeability, function, and development. This may have long-term implications for host-microbe interactions, immunity, and offspring gut-brain axis function.

Biofunctional Materials for Nerve Regeneration

2007 ◽  
Vol 539-543 ◽  
pp. 547-550
Author(s):  
Yu Mi Kim ◽  
Jin Gao ◽  
Blaine Zern ◽  
Ya Dong Wang
Keyword(s):  
Nervous System ◽  
Nerve Regeneration ◽  
Functional Groups ◽  
Biodegradable Polymer ◽  
Neuronal Development ◽  
Neurite Growth ◽  
Functional Restoration ◽  
Ecm Proteins ◽  
New Strategy ◽  
And Function

Most biomaterials widely used in nerve regeneration are either inert or modified with ECM proteins or their epitopes. Neurotransmitters play a key role in neuronal development and function. Thus we decided to investigate the feasibility of using neurotransmitters to create biofunctional materials that actively engage nerve cells to achieve functional restoration after injury of the nervous system. Our data indicated that a properly designed biodegradable polymer with dopamine functional groups was more capable of promoting neurite growth. Such biofunctional materials can potentially provide a new strategy for nerve regeneration.

Mitochondrial contributions to neuronal development and function

2018 ◽  
Vol 399 (7) ◽  
pp. 723-739 ◽  
Author(s):  
Andrea Princz ◽  
Konstantinos Kounakis ◽  
Nektarios Tavernarakis
Keyword(s):  
Nervous System ◽  
Energy Metabolism ◽  
Neuronal Development ◽  
High Energy ◽  
Neuronal Function ◽  
Mitochondrial Energy Metabolism ◽  
Energy Demands ◽  
Technical Advances ◽  
And Function

AbstractMitochondria are critical to tissues and organs characterized by high-energy demands, such as the nervous system. They provide essential energy and metabolites, and maintain Ca2+balance, which is imperative for proper neuronal function and development. Emerging findings further underline the role of mitochondria in neurons. Technical advances in the last decades made it possible to investigate key mechanisms in neuronal development and the contribution of mitochondria therein. In this article, we discuss the latest findings relevant to the involvement of mitochondria in neuronal development, placing emphasis on mitochondrial metabolism and dynamics. In addition, we survey the role of mitochondrial energy metabolism and Ca2+homeostasis in proper neuronal function, and the involvement of mitochondria in axon myelination.

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