Spatiotemporal dynamics of nicotinic acetylcholine receptors and lipid platforms

Abstract: The relationships between neurotransmitter receptors and their membrane environment are complex, mutual (bidirectional) and physiologically important. Some of these relationships are established with subsets of the membrane lipid population, in the form of lipid platforms, lateral heterogeneities of the bilayer lipid having a dynamic chemical composition distinct from that of the bulk membrane. In addition to the equilibrium between the biosynthetic production, exocytic delivery and recycling of receptors on the one hand, and the endocytic internalization on the other, lateral diffusion, clustering and anchorage of receptors at the lipid platforms play key roles in determining the amount of active receptors at the synapse. Mobile receptors traffic between reservoir non-synaptic membranes and the synapse predominantly by thermally driven Brownian motion, and become immobilized at the perisynaptic region or the synapse proper by various mechanisms. These comprise: (a) clustering mediated by homotropic inter-molecular receptor-receptor associations; (b) heterotropic associations with non-receptor scaffolding proteins or the subjacent cytoskeletal meshwork, leading to diffusional “trapping”, and (c) protein-lipid interactions, particularly with the neutral lipid cholesterol. Preceded by a brief introduction on the currently used methods to study protein lateral mobility in membranes, this review assesses the contribution of some of these mechanisms to the supramolecular organization and dynamics of the paradigm neurotransmitter receptor of muscle and neuronal cells—the nicotinic acetylcholine receptor (nAChR). The translational mobility of nAChRs at these two cell surfaces differs in terms of diffusion coefficients and residence intervals at the synapse, which cover an ample range of time regimes. Neuronal α7 nAChRs exhibit diffusion coefficients similar to those of other neurotransmitter receptors and spend part of their lifetime confined to the perisynaptic region of glutamatergic (excitatory) and GABAergic (inhibitory) synapses; they may also be involved in the regulation of the dynamic equilibrium between excitation and inhibition in brain

Nutrition and Central Nervous System

Clinical studies have revealed that depression is accompanied by impaired brain function and cognitive performances or neurodegenerative processes. Moreover, accumulation of oxidative damage has been implicated in aging and various neurological disorders. This chapter aims to integrate the current knowledge on the relation between brain and diverse alterations in nutrition. The mammalian brain is a lipid-rich organ, where lipids content in gray matter is 36–40% lipid. However, the regulation of cholesterol transport from astrocytes to neurons still remains unclear, among other things. In addition to that, micronutrient status can affect cognitive function at all ages. Vitamin deficiency could influence memory function, and might contribute to cognitive impairment and dementia. Deficiency of vitamin A, folate, vitamins B6, B12, and minerals such as Fe and Zn are associated with prevalence of depressive symptoms according to several epidemiological studies. Experimental evidence suggests that resveratrol, vitamins A, C, E, D and folate may block oxidative stress and promote clearance of Aβ peptides. An adequate intake of fruit, nuts, vegetables, cereals, legumes, or fish can prevent the depletion. High dietary intake of saturated fat and low intake of vegetables may be associated with increased risk of Alzheimer’s disease. Supplementation of diets with omega-3 has been shown to have positive effects on cognitive function. The biochemical and molecular mechanism of these alterations of normal brain function has been described. Future studies should also examine how DNA repair deficiency occurs and affects the nervous system, because this could provide a rational basis for therapies in neurodegenerative diseases.Fil: Alvarez, Silvina Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Gomez, Nidia Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Navigatore Fonzo, Lorena Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Sanchez, Emilse Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Gimenez, Maria Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentin