Introduction: Background Material
Nassir H. Sabah in Neuromuscular Fundamentals, 2020
Microglia are small glial cells of the brain and spinal cord that act as microphages by engulfing and digesting damaged neurons, cellular debris, and infectious organisms. They constitute the first and main immune defense of the central nervous system (CNS). Oligodendrocytes in the CNS and Schwann cells in the peripheral nervous system (PNS) provide the myelin sheath of axons, which very effectively increases the conduction speed of the AP (Section 4.2). Astrocytes in the CNS regulate the extracellular environment of neurons by removing excess ions, notably K+ following APs, and by recycling neurotransmitters involved in synaptic transmission. By having processes that terminate on both blood capillaries and neurons, they regulate blood flow and supply neurons with glucose and oxygen. They seem to play a crucial role in many aspects of neuronal operation, as will be elaborated later in Chapters 6 and 7. Ependymal cells line the cavities of the CNS as discussed later (Section 1.3). Glial cells play a key role in the development of the nervous system and in guiding neurons and axons to their destinations. Glia have also been implicated in some pathological conditions, such as chronic pain, motor neuron disease, and Alzheimer’s disease. Unlike neurons, they can divide, and may cause a type of brain tumor known as glioma. It was once believed that neurons that die cannot be replaced. But it has since been shown that neurons can be regenerated from special types of stem cells, and that astrocytes can sometimes change into neurons.
Effects of Cisplatin on the Chick Embryo — A Model for the Analysis of Prenatal Toxicity
Sam Kacew in Drug Toxicity and Metabolism in Pediatrics, 1990
Several basic mechanisms govern the development of the nervous system.27,28 Cell proliferation is, of course, the main mechanism of growth. Mitotic figures can be seen most frequently located in the inner layer of the neural tube (germinal or ependymal layer). At certain sites (cerebral and cerebellar cortices), proliferating cells migrate to the periphery. At all places and times, a certain proportion of the cells resulting from the proliferative process undergoes differentiation into the neuronal or the neuroglial cell lines. In this way, despite the fact that fully differentiated and functional neurons are already present at the early embryonic stages, immature cells in different stages of the differentiation process can be found not only during the embryonic period, but also during most or all of the fetal period. While programmed cell death is a basic mechanism in normal development of the nervous system,28 nonprogrammed, excessive cell death is a frequent teratogenic mechanism. The effects are similar to those produced by inhibition of the mitotic rate as both result in a decreased growth rate. Thus, factors capable of inhibiting mitosis and/or killing immature cells are generally capable of inducing malformations of the disraphiae and obstructive hydrocephalus when acting during the embryonic period, yet are also capable of affecting the development of the brain when acting during the fetal period. Antineoplastic drugs are a good example of teratogens capable of this action.
Pathology, aetiology and pathogenesis
Jeremy Playfer, John Hindle, Andrew Lees in Parkinson's Disease in the Older Patient, 2018
Whatever the cause or causes of PD, it is likely that nigral cell loss occurs via a common pathophysiological pathway, leading to apoptosis (programmed cell death). Cells can die either by necrosis or apoptosis. In necrosis, an external insult is responsible for death, whereas in apoptosis cell death occurs as a result of an intracellular process regulated by genes. Apoptosis is well documented as a normal physiological process in the development of the nervous system.74 More recently, its pathological role in neurodegenerative disorders has been recognised. The identification of apoptosis depends on finding specific morphological changes, including chromatin clumping.75 This is technically difficult and there some controversy remains over whether apoptosis is important in PD.76,77 There is, however, a developing consensus that changes of apoptosis can be identified in the SNc at post-mortem examination. The number of apoptotic nuclei in the SNc in PD at 2% is approximately 10-fold that seen in normal ageing.62
The positive allosteric modulation of GABAA receptors mRNA in immature hippocampal rat neurons by midazolam affects receptor expression and induces apoptosis
Published in International Journal of Neuroscience, 2019
Barbara Sinner, Julia Steiner, Manuela Malsy, Bernhard M. Graf, Anika Bundscherer
The transfer of neurodevelopmental stages of rat hippocampal neurons into human neuronal development is challenging. However, during neuronal development neurons undergo characteristic developmental changes. This includes the switch of the GABAA receptor from excitatory to an inhibitory receptor. In immature neurons, however, the cytosolic Cl−-concentration is higher compared to the mature neuron. Thus, activation of the GABAA receptor results in a depolarization. During maturation, the intracellular Cl−-concentration decreases due to the up-regulation of NKCC1 (Na+K+2Cl−) co-transporter and down-regulation of KCC2 (K+Cl−) co-transporter 2 [9]. The activation of the GABAA receptors increases Cl−-inward current and hyperpolarizes the neuron [9]. The shift from excitatory to inhibitory GABAA receptor activation depends on the species and the examined brain region [10]. In our cultures of immature hippocampal neurons, activation of the GABAA receptor results in a hyperpolarization. The shift from excitation to inhibition can be observed around days 10–12.
Study on the ameliorating effect of miR-221-3p on the nerve cells injury induced by sevoflurane
Published in International Journal of Neuroscience, 2021
Qirui Wang, Xin Tian, Qijuan Lu, Kun Liu, Jiekun Gong
To observe the effects of sevoflurane on hippocampal neurons viability and apoptosis, the sevoflurane model was constructed, and cells were treated with the concentration of 1%, 2% and 3% sevoflurane, respectively. Neural development is a complex and dynamic process, and the viability of neural stem cells directly affects neural development. Drug-induced neuronal apoptosis is also a potential factor affecting neural development [24, 25]. Anesthetic drugs can trigger abnormal apoptotic patterns, and cause neurodegenerative changes in the brain [26]. It has shown that the exposure of sevoflurane may lead to the loss of hippocampal neurons and cognitive dysfunction by inducing the apoptosis of hippocampal cells mediated by endoplasmic reticulum stress [27]. This study revealed the toxic effects of sevoflurane on hippocampal neurons in rats, sevoflurane inhibited the cell viability and promoted apoptosis. These results were consistent with previous studies by Xu Yang et al [28]. Importantly, we observed that miR-221-3p level was decreased by sevoflurane, suggesting that the down-regulation of miR-221-3p was involved in the neuron injury induced by sevoflurane.
Molecular mechanisms governing axonal transport: a C. elegans perspective
Published in Journal of Neurogenetics, 2020
Amruta Vasudevan, Sandhya P. Koushika
Anterograde axonal transport is crucial for neuronal development and function (Morfini et al., 2012). Studies conducted in C. elegans have helped identify several factors that link anterograde axonal transport to neuronal morphology. The Kinesin-1 subunit KLC-2, and VAB-8, a protein with Kinesin-like domains, play an important role in axon guidance and process outgrowth of C. elegans motor and touch sensory neurons (Lai & Garriga, 2004; Su et al., 2006; Tsuboi, Hikita, Qadota, Amano, & Kaibuchi, 2005; Wolf et al., 1998). AEX-3, a GEF for RAB-3, has been identified to be necessary for guidance of the C. elegans AVG neuron, and consequently, the organization of the entire Ventral Nerve Cord (Bhat & Hutter, 2016). It has been proposed that AEX-3 does so by regulating the anterograde trafficking of the Netrin receptor, UNC-5, mediated in part by UNC-104 (Bhat & Hutter, 2016).
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