MOLECULAR NEUROBIOLOGY

Author: ALONSO FERNANDEZ M.EVA.
Year: 2004.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD CC. BIOLÓGICAS.
Place of preparation: FACULTAD CC BIOLÓGICAS.

Summary: The carcinogenic process is a complex process resulting from several successive events. Foremost among these is the proliferation of one or a group of cells that give rise to a so-called tumor cell accumulation. The genesis of this implies an increase in molecular alterations for a certain period until the moment it becomes obvious. The oligodendrogliomas are tumors derived from cells of the oligodendroglía. They have an incidence of approximately 5% of all primary brain tumors and a lOa 25% of intracranial gliomas According to the World Health Organization (WHO), oligodendrogliomas are divided according to their degree histopatólogico and malignancy in: IT grade oligodendrogliomas, oligodendrogliomas grade ID or anaplastic tumors and oligoastrocitomas or mixed (grade TIy ID) component of the series astrocítica and oligodendroglial. Mutacionales and cytogenetic studies have failed to fully explain the genesis and progression of oligodendrogliomas. Although it has been associated loss heterocigosidad of specific chromosomal regions with tumor progression towards forms of ID degree, so far have not been clearly identified from among potential candidate genes, those responsible for this progression. Studies citogenético-moleculares represented the first approach to the understanding of the genetic basis involved in the development of oligodendrogliomas. The changes are the most common allelic loss in 1p and 19q or a combination of both. The frequent coincidence of the loss of 1p and 19q suggested a synergistic effect of both changes confer a selective advantage to oligodendrocytes. Oncosupresores located in lp target genes that might be involved in the formation process are oligodendrogliomas eg p1 [jnk4c, TP73, Patched2, RlZ1 and KIF1B. Losses in 19q indicate a selective advantage based on reduced dose genetics of this region. Studies of alterations of suppressor genes located in this area (BA) (, SEPW1, GLTSCR1 and GLTSCR2) indicate that there is no involvement of children on oligodendrogliomas. Anaplastic tumor progression is associated with multiple genetic and chromosomal abnormalities found in 9p and chromosome 10, which include cell cycle regulatory genes as CDKN2A (TP 15INK4B), CDKN2B (TP 16 INK4A) YPTEN. region 22q is one of the regions that appear most frequently delecionadas in some types of gliomas. Regarding gene located in 22q, an area sometimes delecionada in oligodendrogliomas, IM1hSNF5, NF2 and PARVG are oncosupresores possibly involved in the pathogenesis oligodendroglial. TP53 is the oncosupresor most frequently mutated in human cancer. Following the identification in 1997 of TP7310calizado in lp36.33 and one year later cloning of TP63ITP73Vp51localizado at 3q27, and taking into account that both genes share a 63% homology to the DNA binding domain, it has been suggested that there might be a role oncogénica of these genes or at least a common function with TP53 . Numerous studies have shown the involvement of cell cycle genes drivers in the development of tumors of the nervous system such as RB1, p1O7 and RB2/p130 involved in the beginning of phase G1. chromosomal abnormalities and genetic oligoastrocitomas are quite heterogeneous . tumors These alterations share characteristics of oligodendrogliomas and astrocytomas. Amplification of protooncogenes is an alteration to be considered in the progression of gliomas. Lots of protooncogenes that could act in the pathogenesis oligodendroglial by its location in the genome (MDM4, GAC1, REN1, ELF3) for his role in the cell cycle (CDK4 and MDM2) or relationship with receivers cellular growth factors (HER-2 and PDGFRA). non-heritable genetic alterations that involve alterations in gene expression are calls epigenéticas. mo 8 dificaci 686 n is the most common epigenetic methylation of citosinas located in dinucleótidos CpG. methylation pattern is specific species and tissue. Distribution of dinucleótidos CpG is not uniform, there are regions called CpG islands located in regions 5 'genes accumulate these dinucleótidos and normally are not metiladas. gene silencing suppressor genes or DNA repair by hypermethylation of CpG islands in their epigenético advocates is a mechanism that is involved in the pathogenesis of many tumors. Even the association between multiple genes hipermetilados suggests that the hypermethylation of some gene predisposes others to this process and therefore confers a selective growth advantage in the development of tumors. According to various studies, genes that appear hipermetilados processes and carcinogens that could act in the pathogenesis of oligodendrogliomas are MGMT, TP1 TPJ (jnk4A, RB1, DAPK, THBSI, GSTPI, TP73y TIMP3. Bearing in mind the background genetic and epigenetic involved in the pathogenesis of oligodendrogliomas and ignorance that still exists about its origin and progression, research is needed most profound and detailed information on these aspects.

Author: PILAR CUÉLLAR MARÍA FUENCISLA.
Year: 2005.
University: LEÓN.
Place of defense: FACULTAD DE CIENCIAS BIOLÓGICAS Y AMBIENTALES.
Place of preparation: FACULTAD DE CIENCIAS BIOLÓGICAS Y AMBIENTALES.

Summary: The muscarinic receptors belong to the family of receptors seven transmembrane domains that are coupled to G proteins These receptors recognize specific form of the neurotransmitter acetylcholine, performing functions in the central nervous system related to motor control, regulation of body temperature and learning and memory. During the aging process will produce a series of changes in brain and the loss of functionality of neural connections, a decrease in blood flow, changes in the number of receptors in different systems neurotransmission, and so on. With regard to the cholinergic system, is running the so-called "cholinergic hypothesis of aging", which indicates the loss of cholinergic function that occurs in the central nervous system contributes to the cognitive decline associated with age avanzada.El objective of this work it was the characterization of muscarinic system, the number of recipients and functionality of the same in different brain structures encefálicas of jerbo over aging. The studies and functional receptor autoradiography individuals in a wide range of ages, have shown significant differences in some structures associated with age. This decrease in functionality could be related to the loss of innervation septo-hipocampal that occurs during aging. In cingular cortex was observed an increase in the number of receptor subtypes M2 and M4 along the aging process, while in the same area cortical not show significant differences in functional response for either muscarinic agonists used, giving an insight into the functional importance of muscarinic receptors in the cortex region. Other cortical regions such as cortex entorrinal, had a decrease of stimulation promoted by oxotremorina and carbacol over age. The core talámico anteromedial had an increase in the number of receptors subtype M2 and M3, as well as an increase in the functional response agonist promoted by the muscarinic oxotremorina associated with age. In nucleus talámico anteroventral there was an increase in the level of functional response stimulated by oxotremorina during the aging process. This core has glutamatergic innervation in cortex and hypothalamus, being involved in cognitive functions, so that any reduction in the release of glutamate, as well as cognitive dysfunction that occurs during aging could be related to changes in the muscarinic system. Finally, caudado-putamen, variations in connection with the elderly is a reduction in the stimulation promoted by the agonist oxotremorina.