Brain extracellular matrix: An upcoming target in neurological and psychiatric disorders

Dityatev, Alexander; Seidenbecher, Constanze I.; Morawski, Markus

doi:10.1111/ejn.15336

Cited by 10 publications

(10 citation statements)

References 13 publications

(17 reference statements)

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“…The role of DM genes of the extracellular matrix has already been highlighted in relation to early domestication in fish, and especially for DM changes established already early during development [ 39 ]. At the same time, the brain extracellular matrix is known to have multiple roles in brain development and function, and abnormal alteration of this matrix is increasingly acknowledged as a key etiological factor involved in neurological and psychiatric disorders (see Dityatev et al [ 83 ] for review). In ASD, genes were slightly different and included bone morphogenetic proteins, glutamate receptors, laminins, protocadherins, and semaphorins.…”

Section: Discussionmentioning

confidence: 99%

Fish as Model Systems to Study Epigenetic Drivers in Human Self-Domestication and Neurodevelopmental Cognitive Disorders

Anastasiadi

Piferrer

Wellenreuther

et al. 2022

Genes

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Modern humans exhibit phenotypic traits and molecular events shared with other domesticates that are thought to be by-products of selection for reduced aggression. This is the human self-domestication hypothesis. As one of the first types of responses to a novel environment, epigenetic changes may have also facilitated early self-domestication in humans. Here, we argue that fish species, which have been recently domesticated, can provide model systems to study epigenetic drivers in human self-domestication. To test this, we used in silico approaches to compare genes with epigenetic changes in early domesticates of European sea bass with genes exhibiting methylation changes in anatomically modern humans (comparison 1), and neurodevelopmental cognitive disorders considered to exhibit abnormal self-domestication traits, i.e., schizophrenia, Williams syndrome, and autism spectrum disorders (comparison 2). Overlapping genes in comparison 1 were involved in processes like limb morphogenesis and phenotypes like abnormal jaw morphology and hypopigmentation. Overlapping genes in comparison 2 affected paralogue genes involved in processes such as neural crest differentiation and ectoderm differentiation. These findings pave the way for future studies using fish species as models to investigate epigenetic changes as drivers of human-self domestication and as triggers of cognitive disorders.

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Section: Discussionmentioning

confidence: 99%

Fish as Model Systems to Study Epigenetic Drivers in Human Self-Domestication and Neurodevelopmental Cognitive Disorders

Anastasiadi

Piferrer

Wellenreuther

et al. 2022

Genes

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show abstract

“…The role of DM genes of the extracellular matrix has already been highlighted in relation to early domestication in fish, and especially for DM changes established already early during development [35]. At the same time, the brain extracellular matrix is known to have multiple roles in brain development and function, and abnormal alteration of this matrix is increasingly acknowledged as a key etiological factor involved in neurological and psychiatric disorders (see [80] for review). In ASD, genes were slightly different and included bone morphogenetic proteins, glutamate receptors, laminins, protocadherins and semaphorins.…”

Section: Discussionmentioning

confidence: 99%

Fish as model systems to study epigenetic drivers in human self-domestication and neurodevelopmental cognitive disorders

Anastasiadi

Piferrer

Wellenreuther

et al. 2022

Preprint

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Modern humans exhibit phenotypic traits that are shared across independent domestication events, suggesting the human self-domestication hypothesis. Epigenetic changes may facilitate early self-domestication in humans, since they can be the first layer of response to a novel environment. Here, we argue that fish provide model systems to study epigenetic drivers in human self-domestication. To do this, we compare genes that carry epigenetic changes in early domesticates of European sea bass with 1) anatomically modern humans and 2) neurodevelopmental cognitive disorders with abnormal self-domestication traits, i.e., schizophrenia, Williams syndrome and autism spectrum disorders. We found that genes with epigenetic changes in fish and in modern vs ancient humans were shared and were involved in processes like limb morphogenesis and phenotypes like abnormal snout morphology and hypopigmentation. Moreover, early domestication in fish and neurodevelopmental cognitive impairment in humans affected paralogue genes involved in processes such as neural crest differentiation and ectoderm differentiation. We conclude that parallel epigenetic changes may occur at the initial steps of domestication in absence of deliberate selection in phylogenetically distant vertebrates. These findings pave the way for future studies using fish as models to investigate epigenetic changes as drivers of human-self domestication and as triggers of cognitive disorders.

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“…Digestion, blocking or removal of PNNs impedes functional recovery after a variety of CNS lesions. Deficient PNN numbers are implicated in a number of psychiatric disorders and suggested as therapeutic targets in their treatment ( Dityatev et al, 2021 ). Incorrect assembly of PNNs or degradation of PNN components by excessive MMP activity can lead to the development of epilepsy ( Rankin-Gee et al, 2015 ; Dubey et al, 2017 ; Mencio et al, 2021 ).…”

Section: Mammalian Neuronal Proteoglycansmentioning

confidence: 99%

“…With an appreciation of PNNs and their important contributions to synaptic stability ( Miyata et al, 2018 ), plasticity, memory and cognitive learning in normal brain tissues this has led to the identification of abnormalities in PNN assembly or expression of PNN components associated with particular neurodegerative conditions ( Yamaguchi, 2000 ; Wen et al, 2018 ). Thus PNNs have become a therapeutic focus in the treatment of these conditions ( Dityatev et al, 2006 , 2010 , 2021 ).…”

Section: Mammalian Neuronal Proteoglycansmentioning

confidence: 99%

“…This membrane polarization process is essential for cell signaling and is aberrantly controlled in neurological diseases. Examination of the ECM PGs that control these neural processes has uncovered valuable therapeutic targets ( Soleman et al, 2013 ; Maćkowiak et al, 2014 ; De Luca and Papa, 2016 ; Miyata and Kitagawa, 2016 ; Yang, 2020 ; Dityatev et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Neural Tissue Homeostasis and Repair Is Regulated via CS and DS Proteoglycan Motifs

Hayes

Melrose

2021

Front. Cell Dev. Biol.

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Chondroitin sulfate (CS) is the most abundant and widely distributed glycosaminoglycan (GAG) in the human body. As a component of proteoglycans (PGs) it has numerous roles in matrix stabilization and cellular regulation. This chapter highlights the roles of CS and CS-PGs in the central and peripheral nervous systems (CNS/PNS). CS has specific cell regulatory roles that control tissue function and homeostasis. The CNS/PNS contains a diverse range of CS-PGs which direct the development of embryonic neural axonal networks, and the responses of neural cell populations in mature tissues to traumatic injury. Following brain trauma and spinal cord injury, a stabilizing CS-PG-rich scar tissue is laid down at the defect site to protect neural tissues, which are amongst the softest tissues of the human body. Unfortunately, the CS concentrated in gliotic scars also inhibits neural outgrowth and functional recovery. CS has well known inhibitory properties over neural behavior, and animal models of CNS/PNS injury have demonstrated that selective degradation of CS using chondroitinase improves neuronal functional recovery. CS-PGs are present diffusely in the CNS but also form denser regions of extracellular matrix termed perineuronal nets which surround neurons. Hyaluronan is immobilized in hyalectan CS-PG aggregates in these perineural structures, which provide neural protection, synapse, and neural plasticity, and have roles in memory and cognitive learning. Despite the generally inhibitory cues delivered by CS-A and CS-C, some CS-PGs containing highly charged CS disaccharides (CS-D, CS-E) or dermatan sulfate (DS) disaccharides that promote neural outgrowth and functional recovery. CS/DS thus has varied cell regulatory properties and structural ECM supportive roles in the CNS/PNS depending on the glycoform present and its location in tissue niches and specific cellular contexts. Studies on the fruit fly, Drosophila melanogaster and the nematode Caenorhabditis elegans have provided insightful information on neural interconnectivity and the role of the ECM and its PGs in neural development and in tissue morphogenesis in a whole organism environment.

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Brain extracellular matrix: An upcoming target in neurological and psychiatric disorders

Cited by 10 publications

References 13 publications

Fish as Model Systems to Study Epigenetic Drivers in Human Self-Domestication and Neurodevelopmental Cognitive Disorders

Fish as Model Systems to Study Epigenetic Drivers in Human Self-Domestication and Neurodevelopmental Cognitive Disorders

Fish as model systems to study epigenetic drivers in human self-domestication and neurodevelopmental cognitive disorders

Neural Tissue Homeostasis and Repair Is Regulated via CS and DS Proteoglycan Motifs

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