Endogenous regeneration in the brain is the ability of cells to be involved in the process of repair and regeneration. While the brain has limited capacity for regeneration, endogenous nerve stem cells, as well as many pro-regenerative molecules, can participate in replacing and repairing damaged or diseased neurons and glial cells. Other benefits that can be achieved by using endogenous regeneration can avoid the immune response of the host.
Video Endogenous regeneration
Nerve stem cells in adult brain
During early human development, neural stem cells lie in the germ layers of the developing brain, ventricle and subventricular zones. In brain development, multipotent stem cells (those that can produce different types of cells) are present in these areas, and all of these cells differentiate into nerve cell forms, such as neurons, oligodendrocytes and astrocytes. Long-held beliefs suggest that the multipotence of neural stem cells will be lost in adult human brains. However, only in vitro, using neurosphere and inherent monolayer cultures, stem cells can be found in adult mammalian brains that have demonstrated mutipotent capacity, while in vivo learning is inconclusive. Therefore, the term "nerve ancestor" is used instead of "stem cell" to describe limited regeneration ability in adult brain stem cells.
Neural stem cells (NSCs) are in the subventricular zone (SVZ) of the adult human brain and the dentate gyrus of the adult mammalian hippocampus. Newly formed neurons from this region participate in learning, memory, smell and mood modulation. It has not been determined whether these stem cells are multipotent or not. NSCs of the ripple hippocampus, which can differentiate into dentate granule cells, have evolved into many cell types when studied in culture. However, another in vivo study, using NSC in postnatal SVZ, shows that stem cells are limited to developing into different neuronal sub-type cells in the olfactory bulbus. It is believed that various spatial locations govern the differentiation of neural stem cells.
Maps Endogenous regeneration
Neurogenesis in the central nervous system
Santiago Ramon y Cajal, a neuroscientist pioneer, concluded that the formation of neurons occurs only in the prenatal phase of human development, not after birth. This theory has long been the basic principle of neuroscience. However, by the mid-20th century, evidence of neurogenesis of adult mammals was found in rodent hippocampus and other areas of the brain. In the brain of intact adult mammals, neuroregeneration maintains the function and structure of the central nervous system (CNS). The most adult stem cells in the brain are found in the subventricular zone in the lateral wall of the lateral ventricle. Another area where neurogenesis occurs in the adult brain is the subgranular zone (SGZ) of the dentate gyrus in the hippocampus. While the exact mechanisms that maintain functional NSC in this region are still unknown, NSC has demonstrated the ability to restore neurons and glia in response to certain pathological conditions. However, so far, this regeneration by the NSCs is not enough to restore the function and the full structure of the injured brain. However, endogenous neuroremeneration, unlike using embryonic stem cell implantation, is anticipated to treat a damaged CNS without immunogenesis or tumorigenesis.
Neurogenesis in subgranular zone
Progenitor cells in the dentate gyrus of the hippocampus migrate to nearby locations and differentiate into granular cells. As part of the limbic system, the new hippocampal neurons maintain the functions of mood control, learning and memory. In the dentate gyrus, putative stem cells, called cell type 1, proliferate into type 2 and type 3 cells, which temporarily amplify, the progenitor cells determined by lineage. Type 1 cell in the hippocampus is multipotent in vitro . However, despite evidence that both new neurons and glia are produced in the hippocampus in vivo , there is no definite association of neurogenesis with the type 1 cells shown.
In the hippocampus, newly formed neurons account for only a small fraction of the overall population of neurons. This new neuron has a different electrophysiology than the rest of the neurons. This may be evidence that generating new neurons in SGZ is part of learning and memorizing mammalian activity. Several studies have been conducted to explain the relationship between neruogenesis and learning. In the case of learning, associated with the hippocampal function, the number of neurons increased significantly resulted in SGZ and the survival of new neurons increased if necessary for memory retention. In addition to learning and memorization, neurogenesis in SGZ is also influenced by mood and emotion. With constant, unavoidable stress, which usually results in emotional depression, there is a significant decrease in neurogensis, an effect that can be reversed by treatment with fluoxetine.
Neurogenesis in subventricular zone
The largest NSC population in the brain is found in SVZ. SVZ is considered a micro-environment called "niche stem cell" that maintains NSC capacity for self-renewal and multipotency. Basic fibroblast growth factors (FGF2), hepatocyte growth factor (HGF), Notch-1, sonic hedgehog (SHH), noggin, neurotrophic sili (CNTF) factors, and soluble carbohydrate binding protein, Galectin-1 were reported as factors that retained the properties NSC as in the niche stem cell. Like stem cells in SGZ, progenitor cells in SVZ also differentiate into neurons and form an intermediate cell called a transient amplifier cell (TAC). A recent study reveals that beta-catenin signaling, Wnt? -catenin, regulates TAC differentiation.
The NSC in SVZ has a different capacity to migrate to the olfactory bulb at the anterior end of the telencephalon with a path called rostral migratory flow (RMS). This migration is unique to new neurons in SVZ that neurogenesis of embryos and nerogenesis in other regions of the brain can not perform. Another unique neurogensis in SVZ is neurogenesis by astrocytes. A study conducted by Doetsch (1999) shows that astrocytes in SVZ can differentiate and differentiate into neurons in olfactory bulb. Among the four cell types in SVZ (neuroblast migration, immature precursors, astrocytes, and ependymal cells), migrating neuroblasts and immature precursors are silenced with anti-mitotic agents and astrocytes infected with retroviruses. As a result, neurons that have retroviruses are found in olfactory bulb.
Factors affecting neurogenesis
Neurogenesis in the brain of adult mammals is influenced by various factors, including exercise, stroke, brain insults and pharmacological treatments. For example, acid-induced seizures, antidepressants (fluoxetine), neurotransmitters such as GABA and growth factors (fibroblast growth factor (FGFs), epidermal growth factor (EGF), neuregulins (NRG), vascular endothelial growth factor (VEGF), and factor pigment The NSC's final aim of NSC is determined by the "niche" signal Wnt signaling drives the NSC to the formation of new neurons in SGZ, whereas bone morphogenic proteins (BMPs) promote differentiation of NSC into glia cells in SVZ.
However, in the case of brain injury, neurogenesis does not seem to be enough to repair damaged neurons. Thus, Cajal theory was accepted for a long time. In fact, under interranial physiological conditions, many neurogenesis inhibitors are present (eg, axon growth inhibitor ligand expressed in oligodendrocytes, myelin, NG2-glia, and reactive astrocytes in lesions and degeneration channels, and fibroblasts in scar tissue). The inhibiting ligand binds to the cone-growth receptor on the damaged neuron, which causes repulsive and collapse of growth cones in the damaged area. Among the inhibiting factors, the oligodendrocyte and myelin-inhibited ligand are bound to the membrane, which means that, in the case of injury, these factors are neither regulated nor overexpressed, but from direct contact between whole or degraded (or oligodendrocytes) forming neurons.
However, with scar formation, many types of cells in the brain release growth inhibiting ligands such as the basal lamina component, inhibitory axon guard molecules and chondroitin sulfate proteoglycans. The act of inhibiting these factors can be a protective brain from inflammation. Okano and Sawamoto used a selective elective-selective static mouse model to examine the role of reactive astrocytes. The result is an increase in CD11b-positive inflammatory cell invasion and demyelination.
Apps
Brain damage itself can cause endogenous regeneration. Many studies have proven endogenous regeneration as a possible treatment of brain damage. However, the surrounding tissue inhibitory reactions from the damaged areas must be resolved before treatment results in significant improvements.
Traumatic brain injury
In a study of brain-endogenous regeneration by Scharff and his fellow researchers, the damage to songbird neurons in the brain is regenerated with the same neuronal type in which regeneration occurs (in the case of the study, the hippocampus). However, in places where normal regeneration of neurons does not occur, there is no replacement of damaged neurons. Thus, restoring brain function after brain injury should have limitations. However, current research reveals that neurons are repaired to some extent after damage, from SVZ.
The ability of migrating progenitor cells in a chain shape structure such as SVZ and laterally removing progenitor cells to the wounded region. Along with progenitor cells, the thin astrocytes and blood vessels also play an important role in neuroblast migration, suggesting that blood vessels can act as scaffolds. Other factors that contribute to migration are slit proteins (produced in the choroid plexus) and the gradient (produced by cerebrospinal fluid flow). However, only 0.2% of new neurons survive and function in this study. Increasing neurogenesis can be done by injecting growth factors such as fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF). However, enhanced neurogenesis also has the possibility of epilepsy that results in prolonged seizures.
Parkinson's disease
Although endogenous regeneration methods show some promising evidence in treating brain ischemia, the body of current knowledge regarding promoting and inhibiting endogenous regeneration is not sufficient to treat Parkinson's disease. Both extrinsic and intrinsic modulation of pathological and physiological stimulation prevent progenitor cells from differentiating into dopamine cells. Further research should be done to understand the factors that affect the differentiation of progenitor cells to treat Parkinson's disease.
Although the difficulty in replacing dopamine neurons is disrupted through endogenous sources, recent work suggests that pharmacological activation of endogenous neuronal stem cells or nerve precursors results in strong neuronal rescue and improved motor skills via signal transduction pathways involving STAT3 phosphorylation in serine. residue and subsequent expansion of Hes3 expression (STAT3-Ser/Hes3 Signaling Axis).
References
Source of the article : Wikipedia
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