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Reelin, a Hub Protein during Nervous System Development?
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Reelin, a Hub Protein during Nervous System Development?

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (30 May 2020) | Viewed by 15865

Special Issue Editor

Dr. Pascale Chavis

E-Mail Website1 Website2
Guest Editor
Institut de Neurobiologiede la Méditerranée, Marseille, France
Interests: prefrontal cortex; postnatal maturation; adolescent vulnerability; reelin; extracellular matrix; synaptic plasticity; pathophysiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Reelin is a prominent brain extracellular matrix glycoprotein linked to an extensive signaling complex. Since its discovery and the description of a link between its homozygous loss-of-function mutation and a severe neurological phenotype characterized by a reeling gait in affected mice, reelin has come to be understood as a multifunctional protein and a psychiatric risk factor.

An important contributor at different stages of brain development, reelin is present during embryogenesis, postnatal maturation and plays a role in the physiology of the adult central nervous system. Reelin has recently been found to be highly sensitive to environmental and chronic stressors that lead to dramatic alterations of expression levels. These significant changes in reelin expression and, consequently, to reelin-mediated signaling pathways, could constitute an important trigger of neuropsychiatric disorders.

At the crossroads between cellular properties and physiological functions, this Special Issue aims to gather the latest findings on reelin signaling and function in normal and pathological development of the central nervous system during both pre- and postnatal life. It will present original studies at the cellular or neural network level that include multiscale approaches (structural, functional and behavioral) as well as reviews. It will also encourage studies of the molecular mechanisms associated with reelin signaling and the cellular pathways involved in reelin-mediated pathological brain development.

Dr. Pascale Chavis
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Prenatal development
  • Postnatal maturation
  • Physiology
  • Migration
  • Circuitry
  • Cellular pathways
  • Signal transduction
  • Psychiatric and cognitive disorders
  • Neurodevelopmental disorders

Related Special Issue

Published Papers (3 papers)

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Research

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14 pages, 4234 KiB  
Article
Reduced Reelin Expression in the Hippocampus after Traumatic Brain Injury
by Valentina Dal Pozzo, Beth Crowell, Nicholas Briski, David P. Crockett and Gabriella D’Arcangelo
Biomolecules 2020, 10(7), 975; https://doi.org/10.3390/biom10070975 - 29 Jun 2020
Cited by 10 | Viewed by 3021
Abstract
Traumatic brain injury (TBI) is a relatively common occurrence following accidents or violence, and often results in long-term cognitive or motor disability. Despite the high health cost associated with this type of injury, presently there are no effective treatments for many neurological symptoms [...] Read more.
Traumatic brain injury (TBI) is a relatively common occurrence following accidents or violence, and often results in long-term cognitive or motor disability. Despite the high health cost associated with this type of injury, presently there are no effective treatments for many neurological symptoms resulting from TBI. This is due in part to our limited understanding of the mechanisms underlying brain dysfunction after injury. In this study, we used the mouse controlled cortical impact (CCI) model to investigate the effects of TBI, and focused on Reelin, an extracellular protein that critically regulates brain development and modulates synaptic activity in the adult brain. We found that Reelin expression decreases in forebrain regions after TBI, and that the number of Reelin-expressing cells decrease specifically in the hippocampus, an area of the brain that plays an important role in learning and memory. We also conducted in vitro experiments using mouse neuronal cultures and discovered that Reelin protects hippocampal neuronal cells from glutamate-induced neurotoxicity, a well-known secondary effect of TBI. Together our findings suggest that the loss of Reelin expression may contribute to neuronal death in the hippocampus after TBI, and raise the possibility that increasing Reelin levels or signaling activity may promote functional recovery. Full article
(This article belongs to the Special Issue Reelin, a Hub Protein during Nervous System Development?)
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15 pages, 2123 KiB  
Article
The Effect of Chronic Methamphetamine Treatment on Schizophrenia Endophenotypes in Heterozygous Reelin Mice: Implications for Schizophrenia
by Camilla Hume, Shelley Massey and Maarten van den Buuse
Biomolecules 2020, 10(6), 940; https://doi.org/10.3390/biom10060940 - 22 Jun 2020
Cited by 6 | Viewed by 3083
Abstract
Reelin has been implicated in the development of schizophrenia but the mechanisms involved in this interaction remain unclear. Chronic methamphetamine (Meth) use may cause dopaminergic sensitisation and psychosis and has been proposed to affect brain dopamine systems similarly to changes seen in schizophrenia. [...] Read more.
Reelin has been implicated in the development of schizophrenia but the mechanisms involved in this interaction remain unclear. Chronic methamphetamine (Meth) use may cause dopaminergic sensitisation and psychosis and has been proposed to affect brain dopamine systems similarly to changes seen in schizophrenia. We compared the long-term effect of chronic Meth treatment between heterozygous reelin mice (HRM) and wildtype controls (WT) with the aim of better understanding the role of reelin in schizophrenia. Meth pretreatment induced sensitisation to the effect of an acute Meth challenge on locomotor activity, but it had no effect on baseline PPI or sociability and social preference. In all behavioural models, HRM did not significantly differ from WT at baseline, except spontaneous exploratory locomotor activity which was higher in HRM than WT, and sociability which was enhanced in HRM. Locomotor hyperactivity sensitisation was not significantly different between HRM and WT. Chronic Meth treatment reduced spontaneous locomotor activity to the level of WT. No deficits in PPI or social behaviour were induced by chronic Meth pretreatment in either strain. In conclusion, these data do not support a role of reelin in schizophrenia, at least not in HRM and in the methamphetamine sensitisation model. Full article
(This article belongs to the Special Issue Reelin, a Hub Protein during Nervous System Development?)
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Review

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32 pages, 2345 KiB  
Review
Reelin Functions, Mechanisms of Action and Signaling Pathways During Brain Development and Maturation
by Yves Jossin
Biomolecules 2020, 10(6), 964; https://doi.org/10.3390/biom10060964 - 26 Jun 2020
Cited by 102 | Viewed by 9278
Abstract
During embryonic development and adulthood, Reelin exerts several important functions in the brain including the regulation of neuronal migration, dendritic growth and branching, dendritic spine formation, synaptogenesis and synaptic plasticity. As a consequence, the Reelin signaling pathway has been associated with several human [...] Read more.
During embryonic development and adulthood, Reelin exerts several important functions in the brain including the regulation of neuronal migration, dendritic growth and branching, dendritic spine formation, synaptogenesis and synaptic plasticity. As a consequence, the Reelin signaling pathway has been associated with several human brain disorders such as lissencephaly, autism, schizophrenia, bipolar disorder, depression, mental retardation, Alzheimer’s disease and epilepsy. Several elements of the signaling pathway are known. Core components, such as the Reelin receptors very low-density lipoprotein receptor (VLDLR) and Apolipoprotein E receptor 2 (ApoER2), Src family kinases Src and Fyn, and the intracellular adaptor Disabled-1 (Dab1), are common to most but not all Reelin functions. Other downstream effectors are, on the other hand, more specific to defined tasks. Reelin is a large extracellular protein, and some aspects of the signal are regulated by its processing into smaller fragments. Rather than being inhibitory, the processing at two major sites seems to be fulfilling important physiological functions. In this review, I describe the various cellular events regulated by Reelin and attempt to explain the current knowledge on the mechanisms of action. After discussing the shared and distinct elements of the Reelin signaling pathway involved in neuronal migration, dendritic growth, spine development and synaptic plasticity, I briefly outline the data revealing the importance of Reelin in human brain disorders. Full article
(This article belongs to the Special Issue Reelin, a Hub Protein during Nervous System Development?)
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