scholarly journals Therapeutic Potential of GABAergic Signaling in Myelin Plasticity and Repair

Author(s):  
Daniel Reyes-Haro ◽  
Abraham Cisneros-Mejorado ◽  
Rogelio O. Arellano

Oligodendrocytes (OLs) produce myelin to insulate axons. This accelerates action potential propagation, allowing nerve impulse information to synchronize within complex neuronal ensembles and promoting brain connectivity. Brain plasticity includes myelination, a process that starts early after birth and continues throughout life. Myelin repair, followed by injury or disease, requires new OLs differentiated from a population derived from oligodendrocyte precursor cells (OPCs) that continue to proliferate, migrate and differentiate to preserve and remodel myelin in the adult central nervous system. OPCs represent the largest proliferative neural cell population outside the adult neurogenic niches in the brain. OPCs receive synaptic inputs from glutamatergic and GABAergic neurons throughout neurodevelopment, a unique feature among glial cells. Neuron-glia communication through GABA signaling in OPCs has been shown to play a role in myelin plasticity and repair. In this review we will focus on the molecular and functional properties of GABAA receptors (GABAARs) expressed by OPCs and their potential role in remyelination.

2021 ◽  
Author(s):  
Haipeng Zhou ◽  
Siliang Lu ◽  
Ke Li ◽  
Yinxiang Yang ◽  
Caiyan Hu ◽  
...  

Abstract Oligodendrocyte precursor cells (OPCs), which can differentiate into myelinating oligodendrocytes during embryonic development, are an important potential source for myelin repair or regeneration. To date, OPCs from human sources (hOPCs) remain limited. In this study, we aimed to evaluate the safety and remyelination capacity of hOPCs developed in our laboratory by transplanting them into the lateral ventricles of Sprague–Dawley rats of different ages. The toxicity, biodistribution, and tumor formation abilities of the injected hOPCs were examined by evaluating rats’ vital signs, developmental indicators, neural reflexes, along with hematological, immunological, and pathological assessments. In addition, the hOPCs were transplanted into the corpus callosum of shiverer mice to verify cell myelination efficacy. Overall, our results showed that transplanted hOPCs into young mice showed no toxicity against their organ function or immune system, engrafted only in the brain, and caused no tissue proliferation or tumor formation. In terms of efficacy, the transplanted hOPCs formed myelin in the corpus callosum, alleviated the trembling phenotype of shiverer mice, and promoted normal development. The transplantation of hOPCs is safe and can effectively form myelin in the brain, thereby providing a theoretical basis for the future clinical transplantation of hOPCs.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1302
Author(s):  
Friederike Pfeiffer ◽  
Amin Sherafat ◽  
Akiko Nishiyama

Oligodendrocyte precursor cells (OPCs) display numerous protrusions that extend into the surrounding parenchyma in the brain. Depending on the preparation of the tissue analyzed, these protrusions are more or less visible. We applied six different fixation methods and compared the effect of prolonged and stronger fixation on fluorescence intensity of platelet-derived growth factor receptor alpha, a surface marker of OPCs. Importantly, the fluorescence signal is mostly lost on protrusions as compared to the cell body, which has to be considered for specific analyses. Additionally, we show numerous contacts established between OPCs and the brain vasculature, which will contribute to the understanding of the interactions between these two elements.


Neuroscience ◽  
2004 ◽  
Vol 127 (4) ◽  
pp. 813-820 ◽  
Author(s):  
D.W Hampton ◽  
K.E Rhodes ◽  
C Zhao ◽  
R.J.M Franklin ◽  
J.W Fawcett

e-Neuroforum ◽  
2017 ◽  
Vol 23 (2) ◽  
Author(s):  
Eckart Altenmüller ◽  
Shinichi Furuya

AbstractMusicians with extensive training and playing experience provide an excellent model for studying plasticity of the human brain. The demands placed on the nervous system by music performance are very high and provide a uniquely rich multisensory and motor experience to the player. As confirmed by neuroimaging studies, playing music depends on a strong coupling of perception and action mediated by sensory, motor, and multimodal integration regions distributed throughout the brain. A pianist, for example, must draw on a whole set of complex skills, including translating visual analysis of musical notation into motor movements, coordinating multisensory information with bimanual motor activity, developing fine motor skills in both hands coupled with metric precision, and monitoring auditory feedback to fine-tune a performance as it progresses. This article summarizes research on the effects of musical training on brain function, brain connectivity and brain structure. First we address factors inducing and continuously driving brain plasticity in dedicated musicians, arguing that prolonged goal-directed practice, multi-sensory-motor integration, high arousal, and emotional and social rewards contribute to these plasticity-induced brain adaptations. Subsequently, we briefly review the neuroanatomy and neurophysiology underpinning musical activities. Here we focus on the perception of sound, integration of sound and movement, and the physiology of motor planning and motor control. We then review the literature on functional changes in brain activation and brain connectivity along with the acquisition of musical skills, be they auditory or sensory-motor. In the following section we focus on structural adaptions in the gray matter of the brain and in fiber-tract density associated with music learning. Here we critically discuss the findings that structural changes are mostly seen when starting musical training after age seven, whereas functional optimization is more effective before this age. We then address the phenomenon of de-expertise, reviewing studies which provide evidence that intensive music-making can induce dysfunctional changes which are accompanied by a degradation of skilled motor behavior, also termed “musician’s dystonia”. This condition, which is frequently highly disabling, mainly affects male classical musicians with a history of compulsive working behavior, anxiety disorder or chronic pain. Functional and structural brain changes in these musicians are suggestive of deficient inhibition and excess excitation in the central nervous system, which leads to co-activation of antagonistic pairs of muscles during performance, reducing movement speed and quality. We conclude with a concise summary of the role of brain plasticity, metaplasticity and maladaptive plasticity in the acquisition and loss of musicians’ expertise.


2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.


2020 ◽  
Vol 25 (45) ◽  
pp. 4755-4762 ◽  
Author(s):  
Rodrigo Varas ◽  
Fernando C. Ortiz

: Myelin is a specialized membrane allowing for saltatory conduction of action potentials in neurons, an essential process to achieve the normal communication across the nervous system. Accordingly, in diseases characterized by the loss of myelin and myelin forming cells -oligodendrocytes in the CNS-, patients show severe neurological disabilities. After a demyelinated insult, microglia, astrocytes and oligodendrocyte precursor cells invade the lesioned area initiating a spontaneous process of myelin repair (i.e. remyelination). A preserved hallmark of this neuroinflammatory scenario is a local increase of oxidative stress, where several cytokines and chemokines are released by glial and other cells. This generates an environment that determines cell interaction resulting in oligodendrocyte maturity and the ability to synthesize new myelin. Herein we review the main features of the regulatory aspect of these molecules based on recent findings and propose new putative signal molecules involved in the remyelination process, focused in the etiology of Multiple Sclerosis, one of the main demyelinating diseases causing disabilities in the population.


2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.


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