Analysis of psa-ncam expression in the telencephalon of adult rodents
- Juan Nacher Director/a
Universidad de defensa: Universitat de València
Fecha de defensa: 18 de junio de 2010
- Carlos López García Presidente/a
- Emilio Varea Secretario/a
- Jose Antonio del Rio Fernandez Vocal
- Frédérique Datiche Vocal
- César Venero Núñez Vocal
Tipo: Tesis
Resumen
Neuronal plasticity can be defined as the ability of neuronal cells to react with adaptive changes to intrinsic or extrinsic inputs, not only during early development but also during adulthood.This plasticity is considered to be the basis for learning and memory and it is crucial for adaptive responses to aversive experiences and recovery from brain damage and disease . This adaptive reorganization of neuronal connectivity involves a spectrum of modifications: from molecular to structural plasticity. Neuronal structural plasticity is largely dependent on cell adhesion molecules (CAMs). Among CAMs, NCAM is the most studied protein regarding cellular recognition processes and it is expressed on the surface of most cells.Functional properties of NCAM are strongly influenced by the addition of long chains of a complex sugar, the polysialic acid (PSA). It is well known that principal neurons in the adult cerebral cortex undergo synaptic, dendritic and spine remodeling in response to different stimuli; however, little is known about this structural plasticity in interneurons. Several reports, focused in principal neurons, have described that PSA-NCAM participates in plastic processes such as synaptogenesis or neurite remodeling. However, there is only limited information on the expression of this molecule and its role in the structural plasticity in cortical interneurons. We have found that, apart from immature neurons, PSA-NCAM expression can be found in a subpopulation of mature interneurons generated during embryonic development, which are widely distributed in the adult rodent cerebral cortex. These cells show reduced perisomatic and peridendritic puncta expressing different synaptic markers and receive less perisomatic synapses when compared with interneurons lacking PSA-NCAM expression. These data indicate that PSA-NCAM has an important role in the connectivity of interneurons in the adult CNS and may be implicated in the etiology of certain psychiatric disorders involving alterations in the structure of inhibitory networks. Moreover, PSA-NCAM and doublecortin (DCX), a molecule related to neuronal development, are expressed transiently by new neurons in the adult brain. These molecules are also expressed by a cell population in the rat paleocortex layer II, whose origin, phenotype, and function are not clearly understood. We have classified most of these cells as a new cell type termed tangled cell. Some cells with the morphology of semilunar-pyramidal transitional neurons were also found among this population, as well as some scarce cells resembling semilunar, pyramidal. and fusiform neurons. We have found that none of these cells in layer II express markers of glial cells, mature, inhibitory, or principal neurons. They appear to be in a prolonged immature state, confirmed by the coexpression of DCX, TOAD/Ulip/CRMP-4, A3 subunit of the cyclic nucleotide-gated channel, or phosphorylated cyclic adenosine monophosphate response element--binding protein. Moreover, most of them lack synaptic contacts, are covered by astroglial lamellae, and fail to express cellular activity markers, such as c-Fos or Arc, and N-methyl-d-aspartate or glucocorticoid receptors. We have found that none of these cells appear to be generated during adulthood or early youth and that most of them have been generated during embryonic development, mainly in E15.5.