scholarly journals Programmed cell senescence in the mouse developing spinal cord and notochord

2020 ◽  
Author(s):  
Jorge Antolio Domínguez-Bautista ◽  
Pilar Sarah Acevo-Rodríguez ◽  
Susana Castro-Obregón

AbstractProgrammed cell senescence is a cellular process that seems to contribute to morphogenesis during embryo development, in addition to cell proliferation, migration, differentiation and programmed cell death, and has been observed in evolutionary distant organisms like mammals, amphibians and fish. Programmed cell senescence is a phenotype similar to stress-induced cellular senescence, characterized by the expression of cell cycle inhibitors such as CDKN1A/p21, increased activity of a lysosomal enzyme with beta-galactosidase activity (coined senescence-associated beta-galactosidase) and, most importantly, secretion of growth factors, interleukins, chemokines, metalloproteases, etc., collectively known as a senescent-associated secretory phenotype that instructs surrounding tissue. How wide is the distribution of programmed cell senescence during mouse development and its specific mechanisms to shape the embryo are still poorly understood. Here, we investigated whether markers of programmed cell senescence are found in the developing mouse spinal cord and notochord. We found discrete areas and developmental windows with high senescence-associated beta galactosidase in both spinal cord and notochord; expression of CDKN1A/p21 was documented in epithelial cells of the spinal cord and the notochord. Treatment of mice embryos developed ex-utero in the presence of the senolytic ABT-263 resulted in decrease senescence-associated beta-galactosidase activity and number of motoneurons. Our data suggest that several cell types undergo programmed cell senescence in developing spinal cord and notochord contributing to morphogenesis.Contribution to the Field StatementCellular senescence is a state in which cells no longer divide but have the remarkable ability to secrete signaling molecules that alter the tissue where they reside. In adults, this state is typically induced by stress situations that cause DNA damage so cells with altered genome do not multiply. Senescent cells also form when a tissue is injured; they help to regenerate damaged tissue and contribute to wound healing. Phagocytic cells eliminate them when their function is done, having a transient existence. During vertebrate development some cells acquire a very similar phenotype, coined programmed cell senescence, and interestingly they have been found in regions that organize the pattern of development of some organs. How wide is the distribution of programmed cell senescence during development and how they help to shape the embryo are still poorly understood. We discovered in mice embryos different types of cells with senescent features located in particular regions of the developing nervous system: where motoneurons form and in a region that secrete molecules that instruct the embryo where different types of neurons will be created. We propose that programed cell senescence contributes to the morphogenesis of the nervous system.

Author(s):  
Jorge Antolio Domínguez-Bautista ◽  
Pilar Sarah Acevo-Rodríguez ◽  
Susana Castro-Obregón

Programmed cell senescence is a cellular process that seems to contribute to embryo development, in addition to cell proliferation, migration, differentiation and programmed cell death, and has been observed in evolutionary distant organisms such as mammals, amphibians, birds and fish. Programmed cell senescence is a phenotype similar to stress-induced cellular senescence, characterized by the expression of the cell cycle inhibitors p21CIP1/WAF and p16INK4A, increased activity of a lysosomal enzyme with beta-galactosidase activity (coined senescence-associated beta-galactosidase) and secretion of growth factors, interleukins, chemokines, metalloproteases, etc., collectively known as a senescent-associated secretory phenotype that instructs surrounding tissue. How wide is the distribution of programmed cell senescence during mouse development and its specific mechanisms to shape the embryo are still poorly understood. Here, we investigated whether markers of programmed cell senescence are found in the developing mouse spinal cord and notochord. We found discrete areas and developmental windows with high senescence-associated beta galactosidase in both spinal cord and notochord, which was reduced in mice embryos developed ex-utero in the presence of the senolytic ABT-263. Expression of p21CIP1/WAF was documented in epithelial cells of the spinal cord and the notochord, while p16INK4A was observed in motoneurons. Treatment with the senolytic ABT-263 decreased the number of motoneurons, supporting their senescent phenotype. Our data suggest that a subpopulation of motoneurons in the developing spinal cord, as well as some notochord cells undergo programmed cell senescence.


1981 ◽  
Vol 200 (1) ◽  
pp. 143-151 ◽  
Author(s):  
O P Van Diggelen ◽  
A W Schram ◽  
M L Sinnott ◽  
P J Smith ◽  
D Robinson ◽  
...  

The turnover of lysosomal beta-galactosidase was studied in fibroblast cultures from patients with Gm1-gangliosidosis and combined beta-galactosidase and neuraminidase deficiency, which had 5-10% residual beta-galactosidase activity. beta-Galactosidase was specifically inactivated with the suicide substrate beta-D-galactopyranosylmethyl-p-nitro-phenyltriazene (beta-Gal-MNT) and from the subsequent restoration of enzyme activity in cell cultures turnover times were calculated. By using [3H]beta-Gal-MNT, the hydrolytic activity per molecule of beta-galactosidase was determined. 3H-labelled beta-D-galactopyranosylmethylamine, the precursor of [3H]beta-gal-MNT, was obtained by Raney-nickel-catalysed exchange with 3H2O. The rate of synthesis of beta-galactosidase in normal and all mutant cells tested was found to be 0.4-0.5 pmol/day per mg of cellular protein. The GM1-gangliosidosis cells tested contain the normal amount of 0.5 pmol of beta-galactosidase/mg of protein with a normal turnover time of about 10 days, but only 10% of beta-galactosidase activity per enzyme molecule. Cells with combined beta-galactosidase and neuraminidase deficiency contain only 0.3 pmol of beta-galactosidase/mg of protein with a decreased turnover time of 1 day and normal hydrolytic properties (200 nmol of 4-methylumbelliferyl galactoside/h pmol of beta-galactosidase).


1974 ◽  
Vol 02 (02) ◽  
pp. 121-148 ◽  
Author(s):  
P. R. Burgess

Evidence is presented that the signal that damage has occurred to an animal begins with the activation of receptors which respond specifically to noxious stimuli. In fact, different types of nociceptors are found which respond selectively to different types of damage. The activity of nociceptive sensory fibers influences neurons in the spinal cord which are not activated by other types of somatic stimuli and are thus specific. At higher levels of the nervous system less is known about the physiology of pain and such fundamental questions as the degree to which the cerebral cortex is involved in pain perception have not been answered. It is not known to what extent the mechanisms at higher levels are specific and the significance of convergent systems in which an individual neuron can be excited by a number of different stimuli, both noxious and innocuous, has not been resolved. However, it is argued that the evidence at present most strongly supports the concept that the neural system involved in pain is specific; the activity of neurons in this system either causes pain, or if the level of activity is insufficient, no sensation. Ways in which the activity of this specific system may be modulated are discussed in the context of counterirritation and acupuncture analgesia.


2019 ◽  
Vol 7 (4) ◽  
pp. 372-376
Author(s):  
O. O. Potapov ◽  
O. P. Kmyta ◽  
O. O. Tsyndrenko ◽  
N. O. Dmytrenko ◽  
E. V. Kolomiets ◽  
...  

Spinal cord tumors include tumors developing from its parenchyma, vessels, roots and membranes. The main theory of the formation of spinal cord tumors is the polyetiological dysontogenetic theory. According to this theory, hereditary factors, dysembriogenesis, trauma, carcinogenic effects, viral infection, intoxication, radiation, etc. play an important role in the development of tumors. Although scientists keep finding out more about genetic and environmental factors influencing the development of many types of tumors, spinal tumors are still a relatively unknown subject. Spinal tumors partially contain pathological genes, but in many cases, researchers don't know what causes these genetic changes. Tumors of the central nervous system (CNS) make up 12% of all tumors, tumors of the spinal cord – 3% of nervous system disorders, in the structure of malignant lesions of the CNS – 1,4-5%, occur mainly at the age of 20-60 years. In children, as well as in elderly and senile persons, these tumors are rare. Most often, they develop not from the brain matter, but from the surrounding tissue, and when they increase in size, they compress the spinal cord. Spinal tumors are usually divided into primary and secondary. The group of primary tumors include tumors, originating from the brain matter (intramedullar tumors), and those that grow from the membranes of the brain, roots, vessels (extramedullar tumors). Extramedullar tumors are much more common (in 80% of all spinal tumors) than intramedullar tumors. Extramedullar tumors can be both subdural and epidural. The majority of extramedullar tumors are subdural. Occasionally there are tumors, some of which are located inside the dural sac, and some – outside the dura mater, they are subdural-epidural tumors, as well as epidural-extrovertebral tumors. Among extramedullar tumors the most commonly diagnosed are meningiomas and neurinomas, among intramedullar the most common are ependymomas, less common are astrocytomas and oligodendroglioma. Glioblastomas of the spinal cord is extremely rare; the most common metastases from the posterior fossa are medulloblastomas. Intracerebral tumors of the spinal cord are characterized by greater biological benignity, than similar brain tumors. Extracerebral spinal cord tumors have no such differences in their biological properties. In general, spinal cord tumors are more common in elderly patients. Neurinomas and meningiomas predominate in adults, and ependymomas and dysgenetic tumors (teratoma, epidermoid cysts) – in children. Peculiarities of etiopathogenetic aspects, clinical course, influence on socio-economic factors encourage further improvement of diagnosis and more detailed study of this type of tumors. Materials and methods. The analysis of medical records of patients with spinal cord tumors, who were hospitalized in neurological departments of the Sumy Regional and 4th City Clinical Hospitals in 2015-2018 was carried out. 69 clinical cases were processed in order to investigate the prevalence of spinal cord tumors in the Sumy region, the characteristics of the disease in this group of patients, the leading symptoms, methods of diagnosis and treatment. The analysis of statistical data, obtained after processing of the research materials, was carried out using the licensed version of the IBM SPSS Statistics 17 software. Our study significantly established that, according to the histological structure, in 46 patients (28 women and 18 men) meningiomas were predominant and that in 31 patients they were located at the level of Th6-Th12. Mainly in 42 patients (33 women and 9 men, p<0.05) spinal cord neoplasms were localized at the level of Th6-Th12, with extramedular-intradural tumor location – 57 patients (38 women and 19 men). According to our study, pain syndrome significantly prevailed in 42 patients (35 with extramedular-intradural tumor localization). The study of the histological structure of tumors depending on their localization is an integral part of both diagnosis and treatment, and an important component of predicting the quality of life of the patient.


1999 ◽  
Vol 62 (4) ◽  
pp. 390-393 ◽  
Author(s):  
G. R. SCHMIDT ◽  
K. L. HOSSNER ◽  
R. S. YEMM ◽  
D. H. GOULD

The application of pneumatic-powered air injection stunners (PPAISs), pneumatic-powered stunners (PPSs), and cartridge-fired stunners (CFSs) in commercial beef slaughter plants was evaluated to determine the extent of dissemination of central nervous system tissue. Fifteen beef slaughter plants in the western and central United States were visited to observe stunning methods and the condition of the hearts at postmortem inspection. As inspectors performed the normal opening of the hearts, the research observer evaluated the contents of the heart for the presence of clots and/or visible tissue segments in the right ventricle. In eight plants where PPAISs were used, 33% of hearts examined (n = 1,050) contained large clots in the right ventricles. In the four plants where CFSs were used, 1% of the hearts (n = 480) contained detectable clots. In three plants where the newly modified PPSs were used, 12% of the hearts (n = 450) contained detectable clots. Large segments of spinal cord were detected, collected, photographed, and confirmed histologically from two hearts in a plant that used a PPAIS. Most of the material was found in a single right ventricle and was composed of 10 to 13 cm segments of spinal cord.


‘Nerve and muscle’ begins by describing the different types of cells found in the nervous system. It overviews both the somatic and autonomic nervous systems, how nerves function to initiate and propagate signals, and how anaesthetics work. Mechanisms of transmission are considered at different types of synapse, including neuromuscular and interneuronal synapses, and the use and effects of drugs on the process are discussed. The physiology of skeletal, cardiac, and smooth muscle are compared and contrasted, and the pathology of neuromuscular diseases such as demyelination, myasthenia gravis, motor neuron disease, and spinal cord damage discussed.


1985 ◽  
Vol 101 (5) ◽  
pp. 1990-1998 ◽  
Author(s):  
I Wallis ◽  
L Ellis ◽  
K Suh ◽  
K H Pfenninger

Monoclonal antibody (mAb) 5B4 recognizes in the rat a large, developmentally regulated membrane glycoprotein. The larger form of this antigen (185-255 kD) occurs in the developing nervous system and is present in membranes of nerve growth cones, as determined by analysis of a growth cone particle fraction. An immunochemical characterization of this antigen and of a smaller form (140 kD), sparsely present in the mature nervous system, has been described (Ellis, L., I. Wallis, E. Abreu, and K. H. Pfenninger, 1985, J. Cell. Biol., 101:1977-1989). The present paper reports on the localization by immunofluorescence of 5B4 antigen in cultured cortical neurons, developing spinal cord, and the mature olfactory system. In culture, mAb 5B4 stains only neurons; it is sparsely present in neurons at the onset of sprouting while, during sprouting, it appears to be concentrated at the growth cone and in regions of the perikaryon. In the developing spinal cord, 5B4 labeling is faintly detectable on embryonic day 11 but is intense on fetal day 13. At this stage, the fluorescence is observed in regions of the cord where axonal growth is occurring, while areas composed of dividing or migrating neural cells are nonfluorescent. With maturation of the spinal cord, this basic pattern of fluorescence persists initially, but the staining intensity decreases dramatically. In the adult, faint fluorescence is detectable only in gray matter, presumably indicating the presence of the 140 kD rather than the fetal antigen. The only known structure of the adult mammalian nervous system where axonal growth normally occurs is the olfactory nerve. mAb 5B4 intensely stains a variable proportion of olfactory axons in the mucosa as well as in the olfactory bulb. Based on both immunochemical and immunofluorescence data, the 5B4 antigen of 185-255 kD is associated specifically with growing neurons, i.e., neurons that are generating neurites.


1989 ◽  
Vol 9 (5) ◽  
pp. 2269-2272
Author(s):  
J F Caubet

I show, by in situ hybridization, that c-fos is expressed in the nervous system during mouse development. This expression was found to be restricted to specific regions at late stages of development (day 16 postcoitum), particularly to the spinal cord, dorsal root ganglia, and olfactory lobe. The c-fos protein may play a role in the maturation of these structures by activating specific genes.


Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 100
Author(s):  
Alexandra Proshchina ◽  
Victoria Gulimova ◽  
Anastasia Kharlamova ◽  
Yuliya Krivova ◽  
Valeriy Barabanov ◽  
...  

Spaceflight may cause hypogravitational motor syndrome (HMS). However, the role of the nervous system in the formation of HMS remains poorly understood. The aim of this study was to estimate the effects of space flights on the cytoskeleton of the neuronal and glial cells in the spinal cord and mechanoreceptors in the toes of thick-toed geckos (Chondrodactylus turneri GRAY, 1864). Thick-toed geckos are able to maintain attachment and natural locomotion in weightlessness. Different types of mechanoreceptors have been described in the toes of geckos. After flight, neurofilament 200 immunoreactivity in mechanoreceptors was lower than in control. In some motor neurons of flight geckos, nonspecific pathomorphological changes were observed, but they were also detected in the control. No signs of gliosis were detected after spaceflight. Cytoskeleton markers adequately reflect changes in the cells of the nervous system. We suggest that geckos’ adhesion is controlled by the nervous system. Our study revealed no significant disturbances in the morphology of the spinal cord after the prolonged space flight, supporting the hypothesis that geckos compensate the alterations, characteristic for other mammals in weightlessness, by tactile stimulation.


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