Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibroblast growth factor-2 (FGF-2) was injected into mouse cerebral ventricles at embryonic day (E) 14 in utero and its effects on developing brain morphology and expression of various cell- or differentiation-associated protein markers in the cerebral cortex were examined. High doses of FGF-2 (200 or 300 ng) caused encephalic alternations such as deformation of the calvarium, enlargement of the ventricular spaces, and thinning of the cerebral cortex. There was no gross abnormality in the alignment of the cerebral neuronal layers, however, both cell number and cell density of the upper layers (II/III) and the lower layers (IV-VI) of the cerebral cortex were increased. Brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase, nestin, and microtubule-associated protein 2 were aberrantly or ectopically expressed in the deep areas of the cerebral cortex. A substantial number of these cells coexpressed these antigens. These observations demonstrate that a subpopulation of neurons in the cortical deep layer abnormally differentiated or partly sustained their immature state following a single administration of FGF-2 at E14. Developmental analysis of localization of BDNF-positive cells suggested that the abnormality started around P5. Furthermore, cell migration was not affected by FGF-2 administration. FGF-2 seems to play predominant roles in the proliferation of neuronal precursors and in neuronal differentiation in the developing mouse cerebral cortex even at relatively late stages of brain neurogenesis.
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PMID:Administration of FGF-2 to embryonic mouse brain induces hydrocephalic brain morphology and aberrant differentiation of neurons in the postnatal cerebral cortex. 1149 57

TLX is an orphan nuclear receptor that is expressed exclusively in vertebrate forebrains. Although TLX is known to be expressed in embryonic brains, the mechanism by which it influences neural development remains largely unknown. We show here that TLX is expressed specifically in periventricular neural stem cells in embryonic brains. Significant thinning of neocortex was observed in embryonic d 14.5 TLX-null brains with reduced nestin labeling and decreased cell proliferation in the germinal zone. Cell cycle analysis revealed both prolonged cell cycles and increased cell cycle exit in TLX-null embryonic brains. Increased expression of a cyclin-dependent kinase inhibitor p21 and decreased expression of cyclin D1 provide a molecular basis for the deficiency of cell cycle progression in embryonic brains of TLX-null mice. Furthermore, transient knockdown of TLX by in utero electroporation led to precocious cell cycle exit and differentiation of neural stem cells followed by outward migration. Together these results indicate that TLX plays an important role in neural development by regulating cell cycle progression and exit of neural stem cells in the developing brain.
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PMID:Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain. 1790 Nov 27

Mechanisms of cardiac regeneration following transmural myocardial infarction were analysed in rat hearts using immunohistochemistry for a-SMA, caspase-3, Ki-67 and nestin markers. Seven weeks after experimental myocardial infarction, two different types of healing processes were revealed in rats with and without aneurysmatic bulging of the left ventricular wall. Besides thinning of the ventricular wall, three zones characterized both types of scars: the scar zone (divided into central and peripheral parts), the peri-infarct zone and the border zone. The main difference between the types of scars was the presence of a central necrotic zone inside the aneurysmatic wall, while connective tissue with myofibroblasts characterized the same zone in non-bulging wall. Apoptotic caspase-3 positive cells were found in the granulation tissue of the border zone in aneurysmatic scar, while in non-bulging scar they characterized all three zones. Proliferating Ki-67 positive cells displayed reverse expression pattern compared to apoptotic cells. Quantification of a-SMA positive cells revealed 60% a-SMA positive cells inside the central part of the aneurysmatic scar zone and 39% in invaginating areas, versus 19% in non-invaginating areas of the peripheral zone, but only 30% in the peripheral part of the non-bulging scar zone. Nestin positive cells were found in both types of scars, but with different distribution. These results suggest that even seven weeks after myocardial infarction, the healing processes in non-bulging scars are in chronic phase, while aneurysmatic scars are still in subacute phase. Histological differences in scar healing might be important for functional properties of the heart wall and for heart recovery prognosis.
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PMID:Histological differences in healing following experimental transmural infarction in rats. 2088 31

The Pak4 serine/threonine kinase regulates cytoskeletal organization, and controls cell growth, proliferation, and survival. Deletion of Pak4 in mice results in embryonic lethality prior to embryonic day 11.5. Pak4 knockout embryos exhibit abnormalities in the nervous system, the heart, and other tissues. In this study a conditional deletion of Pak4 was generated in order to study the function of Pak4 in the development of the brain. Nervous system-specific conditional deletion of Pak4 was accomplished by crossing mice with a floxed allele of Pak4 with transgenic mice expressing Cre recombinase under the control of the nestin promoter. The conditional Pak4 knockout mice were born normally, but displayed growth retardation and died prematurely. The brains showed a dramatic decrease in proliferation of cortical and striatal neuronal progenitor cells. In vitro analyses revealed a reduced proliferation and self-renewing capacity of neural progenitor cells isolated from Pak4 knockout brains. The mice also exhibited cortical thinning, impaired neurogenesis and loss of neuroepithelial adherens junctions. By the time the mice died, by 4weeks after birth, severe hydrocephalus could also be seen. These results suggest that Pak4 plays a critical role in the regulation of neural progenitor cell proliferation and in establishing the foundation for development of the adult brain.
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PMID:A key role for Pak4 in proliferation and differentiation of neural progenitor cells. 2138 68

Localised brain tissue damage activates surrounding astrocytes, which significantly influences subsequent long-term pathological processes. Most existing focal brain injury models in rodents employ craniotomy to localise mechanical insults. However, the craniotomy procedure itself induces gliosis. To investigate perilesional astrocyte activation under conditions in which the skull is intact, we created focal brain injuries using light exposure through a cranial window made by thinning the skull without inducing gliosis. The lesion size was maximal at ~ 12 h and showed substantial recovery over the subsequent 30 days. Two distinct types of perilesional reactive astrocyte, identified by GFAP upregulation and hypertrophy, were found. In proximal regions the reactive astrocytes proliferated and expressed nestin, whereas in regions distal to the injury core the astrocytes showed increased GFAP expression but did not proliferate, lacked nestin expression, and displayed different morphology. Simply making the window did not induce any of these changes. There were also significant numbers of neurons in the recovering cortical tissue. In the recovery region, reactive astrocytes radially extended processes which appeared to influence the shapes of neuronal nuclei. The proximal reactive astrocytes also formed a cell layer which appeared to serve as a protective barrier, blocking the spread of IgG deposition and migration of microglia from the lesion core to surrounding tissue. The recovery was preceded by perilesional accumulation of leukocytes expressing vascular endothelial growth factor. These results suggest that, under intact skull conditions, focal brain injury is followed by perilesional reactive astrocyte activities that foster cortical tissue protection and recovery.
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PMID:Astrocyte activation and wound healing in intact-skull mouse after focal brain injury. 2301 65