Pattern computation in neural communication systems

Biological data suggests that activity patterns emerging in small- and large-scale neural systems may play an important role in performing the functions of the neural system, and in particular, neural computations. It is proposed in this paper that neural systems can be understood in terms of pattern computation and abstract communication systems theory. It is shown that analysing high-resolution surface EEG data, it is possible to determine abstract probabilistic rules that describe how emerging activity patterns follow earlier activity patterns. The results indicate the applicability of the proposed approach for understanding the working of complex neural systems.     

Molecular mechanisms involved in the hormonal prevention of aging in the rat

Previous data from our group have provided support for the role of GH, melatonin and estrogens in the prevention of aging of several physiological parameters from bone, liver metabolism, vascular activity, the central nervous system (CNS), the immune system and the skin. In the present work data on the molecular mechanisms involved are presented. A total of 140 male and female rats have been submitted to different treatments over 10 weeks, between 22 and 24 months of age. Males have been treated with GH and melatonin. Females were divided in two groups: intact and castrated at 12 months of age. The first group was treated with GH and melatonin and the second with the two latter compounds and additionally with estradiol and Phytosoya^®. Aging was associated with a reduction in the number of neurons of the hylus of the dentate gyrus of the hippocampus and with a reduction of neurogenesis. GH treatment increased the number of neurons but did not increase neurogenesis thus suggesting a reduction of apoptosis. This was supported by the reduction in nucleosomes and the increase in Bcl2 observed in cerebral homogenates together with an increase in sirtuin2 and a reduction of caspases 9 and 3. Melatonin, estrogen and Phytosoya^® treatments increased neurogenesis but did not enhance the total number of neurons. Aging induced a significant increase in mitochondrial nitric oxide in the hepatocytes, together with a reduction in the mitochondrial fraction content in cytochrome C and an increase of this compound in the cytosolic fraction. Reductions of glutathione peroxidase and glutathione S-transferase were also detected, thus indicating oxidative stress and possibly apoptosis. Treatment for 2.5 months of old rats with GH and melatonin were able to significantly and favourably affect age-induced deteriorations, thus reducing oxidative damage. Keratinocytes obtained from old rats in primary culture showed an increase in lipoperoxides, caspases 8 and 3 as well as a reduction in Bcl2 leading to enhanced number of nucleosomes that was also restored upon treatments with GH and melatonin. In conclusion, GH and melatonin treatment seem to have beneficial effects against age-induced damage in the CNS the liver and the skin through molecular mechanisms reducing oxidative stress and apoptosis.     

Molecular mechanisms of neural crest induction

The neural crest is an embryonic cell population that originates at the border between the neural plate and the prospective epidermis. Around the time of neural tube closure, neural crest cells emigrate from the neural tube, migrate along defined paths in the embryo and differentiate into a wealth of derivatives. Most of the craniofacial skeleton, the peripheral nervous system, and the pigment cells of the body originate from neural crest cells. This cell type has important clinical relevance, since many of the most common craniofacial birth defects are a consequence of abnormal neural crest development. Whereas the migration and differentiation of the neural crest have been extensively studied, we are just beginning to understand how this tissue originates. The formation of the neural crest has been described as a classic example of embryonic induction, in which specific tissue interactions and the concerted action of signaling pathways converge to induce a multipotent population of neural crest precursor cells. In this review, we summarize the current status of knowledge on neural crest induction. We place particular emphasis on the signaling molecules and tissue interactions involved, and the relationship between neural crest induction, the formation of the neural plate and neural plate border, and the genes that are upregulated as a consequence of the inductive events.     

Molecular remodeling mechanisms of the neural somatodendritic compartment

Neuronal cells use the process of vesicle trafficking to manipulate the populations of neurotransmitter receptors and other membrane proteins. Long term potentiation (LTP) is a long-lived increase in synaptic strength between neurons and increases postsynaptic dendritic spine size and the concentration of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptor (AMPAR) located in the postsynaptic density. AMPAR is removed from the cell surface via clathrin-mediated endocytosis. While the adaptor protein 2 (AP2) complex of endocytosis seems to have the components needed to allow temporal and spatial regulations of internalization, many accessory proteins are involved, such as epidermal growth factor receptor phosphorylation substrate 15 (Eps15). A sequence of repeats in the Eps15 protein is known as the Eps15 homology (EH) domain. It has affinity for asparagine-proline-phenylalanine (NPF) sequences that are contained within vesicle trafficking proteins such as epsin, Rab11 family interacting protein 2 (Rab11-FIP2), and Numb. After endocytosis, a pool of AMPAR is stored in the endosomal recycling compartment that can be transported to the dendritic spine surface upon stimulation during LTP for lateral diffusion into the postsynaptic density. Rab11 and the Eps15 homologue EHD1 are involved in receptor recycling. EHD family members are also involved in transcytosis of the neuronal cell adhesion molecule neuron-glia cell adhesion molecule (NgCAM) from the somatodendritic compartment to the axon. Neurons have a unique morphology comprising many projections of membrane that is constructed in part by the effects of the Eps15 homologue, intersectin. Morphogenesis in the somatodendritic compartment is becoming better understood, but there is still much exciting territory to explore, especially regarding the roles of various EH domain-NPF interactions in endocytic and recycling processes.     

Molecular mechanisms of hormonal activity. I. receptors. neuromediators. systems with second messengers

Hormone signal transfer along all of the cell compartments including nucleus is powered by signal transduction systems. Characteristics and importance of hormone receptors, principal components, functional mechanisms, and biological role of different systems with second messengers are described. Considerable examples of the importance of these systems for medicine are adduced. The drugs modifying these systems comprise more than 65% of contemporary medicines.Translated from Biokhimiya, Vol. 70, No. 1, 2005, pp. 33–50.Original Russian Text Copyright © 2005 by Kulinsky, Kolesnichenko.     

Molecular mechanisms of segmental patterning in the vertebrate hindbrain and neural crest

Recent work has shown that segmentation underlies the patterning of the vertebrate hindbrain and its neural crest derivatives. Several genes have been identified with segment-restricted expression, and evidence is now emerging regarding their function and regulatory relationships. The expression patterns of Hox genes and the phenotype of null mutants indicate roles in specifying segment identity. A zinc finger gene Krox-20 is a segment-specific regulator of Hox expression, and it seems probable that retinoic acid receptors also regulate Hox genes in the hindbrain. The receptor tyrosine kinase gene Sek may mediate cell-cell interactions that lead to segmentation. These studies provide a starting point for understanding the molecular basis of segmental patterning in the hindbrain.     

Molecular mechanisms of synaptic specificity in developing neural circuits

The function of the brain depends on highly specific patterns of connections between populations of neurons. The establishment of these connections requires the targeting of axons and dendrites to defined zones or laminae, the recognition of individual target cells, the formation of synapses on particular regions of the dendritic tree, and the differentiation of pre- and postsynaptic specializations. Recent studies provide compelling evidence that transmembrane adhesion proteins of the immunoglobulin, cadherin, and leucine-rich repeat protein families, as well as secreted proteins such as semaphorins and FGFs, regulate distinct aspects of neuronal connectivity. These observations suggest that the coordinated actions of a number of molecular signals contribute to the specification and differentiation of synaptic connections in the developing brain.     

Cell junctions and intercellular communication

Summary We have compared intercellular communication in normal and regenerating rat liver. Gap junctions are greatly reduced in size and numbers 29 to 35 hr after hepatectomy, but we still find some 90% of hepatocytes coupled by electrophysiological criteria. The spread of dyes such as carboxyfluorescein however is very limited in the regenerating organs as compared to the situation in the controls. We show how the apparent discrepancies between morphological and physiological data can be reconciled. We also present a summary of preliminary findings on the biosynthesis of gap junction protein and some of the conclusions one can draw from the sequence of 58 amino acids at the amino terminal of the protein. Presented in the symposium on Molecular and Morphological Aspects of Cell-Cell Communication at the 31st Annual Meeting of the Tissue Culture Association, St. Louis, Missouri, June 1–5, 1980. The original research described was supported by Grants GM 06965 and RR 07003 from the National Institute of Health, and funds from the North-west Area Foundation. David Meyer and Barbara Yancey were the recipients of NIH postdoctoral fellowships (NS 06240 and AM05700). This symposium was supported in part by Contract 263-MD-025754 from the National Cancer Institute and the Fogarty International Center.     

Colonial organization and intercellular communication in microorganisms

This review covers the modern concepts and recent data demonstrating the integrity and coherence of microbial populations (colonies, biofilms, etc.) as peculiar “superorganisms.” Special attention is given to such relevant phenomena as apoptosis, bacterial altruism, quorum effects, collective differentiation of microbial cells, and the formation of population-level structures such as an extracellular matrix. Emphasis is placed on the channels and agents of intercellular communication in microbial populations. The involvement of a large number of evolutionarily conserved communicational facilities and patterns of intercellular interactions is underscored. Much attention is also given to the role of colonial organization and intercellular communication in parasite/commensal/symbiont-multicellular host organism systems.     

Gap junction-mediated intercellular communication in the immune system

Immune cells are usually considered non-attached blood cells, which would exclude the formation of gap junctions. This is a misconception since many immune cells express connexin 43 (Cx43) and other connexins and are often residing in tissue. The role of gap junctions is largely ignored by immunologists as is the immune system in the field of gap junction research. Here, the current knowledge of the distribution of connexins and the function of gap junctions in the immune system is discussed. Gap junctions appear to play many roles in antibody productions and specific immune responses and may be important in sensing danger in tissue by the immune system. Gap junctions not only transfer electrical and metabolical but also immunological information in the form of peptides for a process called cross-presentation. This is essential for proper immune responses to viruses and possibly tumours. Until now only 40 research papers on gap junctions in the immune system appeared and this will almost certainly expand with the increased mutual interest between the fields of immunology and gap junction research.     

Studies on coexistence and intercellular communication

Mouse ascites tumor cells (MAT-cells) were co-cultured with mesothelial cells of the mouse. During early stages of coexistence (30–60 min) the mesothelial cells show finger-like protrusions formed mostly at their flanks pointing towards MAT-cells in the neighbourhood. Obviously there is a directional response of the mesothelial cells to the existence of MAT-cells. The mesothelial cells are the more active partner at the beginning of coexistence. Later on MAT-cells also develop fingerlike protrusions which grow towards the mesothelial cells. A network of fingerlike protrusions is formed in the region between MAT-cells and mesothelial cells when they come near to each other. The advantages of the system serving as a model for investigations on intercellular communication are discussed.