Multiple neuronal and glial mechanisms can be involved in the response to the activation of nicotinic receptors

Peer Reviewe

Obesity: A risk for Alzheimer's disease? I. Common molecular mechanisms

Obesity is a recognized risk factor for cardiovascular diseases and the main responsible for the resistance to the action of insulin, a state that precedes the development of diabetes type 2. In the last years, researches have demonstrated that there are also common molecular mechanisms between obesity and Alzheimer's disease, to be the more likely pathological link a state of insulin resistance, which is mediated by inflammation. If the brain dysfunction in Alzheimer's effectively shares underlying mechanisms with obesity, certain intracellular signaling molecules might be involved in both diseases. Identification of these molecules and their consideration as therapeutic targets would represent a breakthrough in the understanding of the mechanisms of these diseases, and an excellent strategy in the development of new therapies for both pathologic conditions. In this work the last hypothesis linking obesity with Alzheimer's disease are reviewed. Adipose tissue dysfunction and consequent accumulation of ectopic fat as a cause of inflammation and insulin resistance systemic conditions obesity characteristics are described. It also highlights these peripheral systemic pathological states as primarily responsible for neuroinflammation and insulin resistance in the brain that would lead to the neuronal dysfunction and cognitive impairment found in Alzheimer's disease.Peer Reviewe

Variability in the effects of nicotine on different regions of the brain: Changes in the concentration of superoxide dismutase isoforms

© 2014 Bentham Science Publishers. Previous studies have shown that rats subjected to subchronic treatment with nicotine experience changes in COX-2 (a marker of pro-inflammatory systems) and accumulate lipid hydroperoxides (a marker of oxidative stress) in the CNS (CNSMC, 2010; 10:180-206) (hippocampus, frontoparietal cortex and cerebellar cortex). Such changes are specific to each region since each contains different types of neuronal and glial cells with different nicotine receptors. They also differ in animals exposed to a source of oxidative stress, such as D-amphetamine. This paper discusses the changes in other markers of oxidative stress - the isozymes of superoxide dismutase Mn-SOD and Cu/Zn-SOD - in nicotine- and nicotine + D-amphetamine-treated rats. The biochemical and histochemical changes observed were specific to each region (in general very marked in the frontoparietal cortex and the hippocampus but less so in the cerebellar cortex) and each type of neuronal and glial cell. The SODs induced by nicotine may exert a neuroprotective effect via the reduction of oxidative stress. This might be beneficial in the treatment of neurodegenerative diseases. The fact that nicotine did not greatly increase the SODs in the rats treated with D-amphetamine may indicate that the effect of nicotine is partially or totally abolished in situations of oxidative stress. However, since ROS and lipid hydroperoxide levels are also reduced when nicotine is administered to such animals, it could be argued that nicotine is beneficial.Peer Reviewe

New concepts on the functionality of the nervous system: The revolution of the glial cells. I. The neuro-glial relationships | Nuevos conceptos sobre la funcionalidad del sistema nervioso: la revolución de las células gliales. I. Las relaciones neuro-gliales

From birth to death, neurons are actively and dynamically accompanied by neuroglial cells in a very close morphological and functional relationship. The results of their study in the last years revolutionized the concepts about the functionality of the CNS. Classically, three families of these cells in the CNS have been classically considered: astroglia, oligodendroglia and microglia. Many types and subtypes have been described by morphological and immunocytochemical methods, including NGR2+ cells, with a wide variety of pathophysiological effects on the neurons and neuronal circuits. Now, all these elements are considered of paramount importance in all proposed theories for explaining any physiological or pathological process in the CNS because they are involved in both, neuroprotection/neurorepair and neurodegeneration. Glio-glial, glio-neuronal and neuro-glial cell signaling pathways and glio-transmission are essential phenomena that support the brain functions, from a simple reflex to the most sophisticated higher mental function. Glioplasticity is a parallel phenomenon to neuroplasticity for optimizing the function of the neuronal circuits. Moreover, they possess the ability to change to a reactive status (gliosis), in which new functions are developed in their relationships with the neurons.Peer Reviewe

Diversity and variability of the nicotine effects on different brain cortical regions. Therapeutic and toxicologic implications

Peer Reviewe

Histochemical electron microscopic study of the enzyme glutamate dehydrogenase (GD) in post-natal developing cerebellum

The histochemical localization of GD has been studied at electron microscopic level, in cerebella of the rat, chicken and duck, during post-natal development. Immature and well-developed structures have been considered. The adult pattern was reached by 45-day old rats and by 30-day old chickens, but in ducks a general pattern exists at 24 hr after birth. Biochemical study of the GD activity showed an increase during development in the rat and chicken, but the highest level, found in the duck, remained almost constant. Results are discussed against cerebellar development, metabolic compartmentation, neuroplasmic flow, and neurotransmission. In general, GD activity develops in parallel to the cerebellar circuits performance.Peer Reviewe

Diversity and variability of the effects of nicotine on different cortical regions of the brain. Therapeutic and toxicological implications

Nicotine/nicotine agonists or allosteric modulators of nicotine receptors have been suggested as the most important therapeutic agents in the prevention and clinical control of cognitive impairment which characteryze neuropsychiatric and neurodegenerative disorders such as schizophrenia, attention deficit/hyperactivity disorder and Alzheimer's disease. Both clinical studies and animal experiments support the important role of the nicotinic systems in learning, different kind of memory and cognition. For development of nicotinic treatments we have a well characterized lead compound, nicotine. However, the neural nicotinic mechanisms underlying cognitive functions are not well known because the side effects of nicotine overdose have hindered the development of this therapeutical line. The new development of non-toxic, brain specific nicotine drugs need a full knolewdge of these mechamism and a reevaluation of the nicotine effects. This review aims to analize the diferent kind of effects of nicotine on the Central Nervous System (CNS), especially on the cortex and hippocampus. Nicotine effects are, theorically and/or practically, of variable character depending on dayly dose and time of treatment; on the subtype and density of the different nicotinic receptors existing in the distinct brain regions; on the processes of desensitization and tolerance of nicotinic receptors and on other neuronal factors. Nicotine produces the above mentioned activation of the cognitive functions acting directly or indirectly on cortical neurons. In some experiments, high doses of nicotine can impair memory. This substance induces increases in the glycolytic pahtway and Krebs cycle of neurons, as well as brain blood flow. Nicotine also produces an increase in NGF immunoreactivity in frontoparietal cortex. All these neuronal changes may cause different positive effects such as neuroprotection, neuroplasticity and better preformance of synaptic circuits. The benefit of other neuronal changes can be matter of discussion such as some modifications in synaptic transmission, the COX-2 increase in frontoparietal cortex and hippocampus or the changes in the antioxidant systems. Finally, other neuronal changes can be of negative effect such as the induction of apoptosis and oxidative stress (DNA damage, ROS and lipid peroxide increase). All these described effects explain both the beneficial and neurotoxic consequeces of the activation of the nicotinic receptors. The diversity and variability of the nicotinic effects should take into account when nicotine agonists will be used as a possible cognitive treatment. © 2010 Bentham Science Publishers Ltd.Peer Reviewe

New concepts on the functionality of the nervous system: The revolution of the glial cells. II. Glial responses keys in the pathogenesis and treatment of diseases of SN

All members of the families of the neuroglia have the ability to adopt a reactive state (>gliosis> in general, >astrogliosis> >oligodendrogliosis> and >microgliosis> in its specific form) face to situations where importantly is modified homeostasis of the nervous tissue and / or normal functional dynamics of neurons and their accompanying neuroglial cells (trauma, neurotoxicity, infections, neurodegenerative processes). In this reactive state, neuroglial cells become >new cells with new functions> because a significant change of their cellular functions occurs, mainly by the expression of new genes. Thus they become major players on the different stage of the new SN pathological situations. Activation of neuroglia cells is initially beneficial, aiming to solve the pathological changes, but it can turn detrimental to nerve tissue. Also, in recent years, it has been found that also the lack of reactive responses or the existence of >maladaptative responses> of the different neuroglial cells as well as the involution or regression of these cells, are important sources of nervous pathology. Studies of these different types of reactive glial cells have significantly expanded the knowledge we had about the pathogenesis of diseases of the SN. Moreover, many studies are revealing that they may be important to define new therapeutic drug targets or create new cell therapies to control the progress of the >pathogenic cascades>, through activating neuroprotection-neurorepair and/or inhibiting the neurotoxicity-neurodegeneration.Peer Reviewe

Brain local and regional neuroglial alterations in alzheimer¿s disease: Cell types, responses and implications

From birth to death, neurons are dynamically accompanied by neuroglial cells in a very close morphological and functional relationship. Three families have been classically considered within the CNS: astroglia, oligodendroglia and microglia. Many types/subtypes (including NGR2+ cells), with a wide variety of physiological and pathological effects on neurons, have been described using morphological and immunocytochemical criteria. Glio-glial, glio-neuronal and neuro-glial cell signaling and gliotransmission are phenomena that are essential to support brain functions. Morphofunctional changes resulting from the plasticity of all the glial cell types parallel the plastic neuronal changes that optimize the functionality of neuronal circuits. Moreover, neuroglia possesses the ability to adopt a reactive status (gliosis) in which, generally, new functions arise to improve and restore if needed the neural functionality. All these features make neuroglial cells elements of paramount importance when attempting to explain any physiological or pathological processes in the CNS, because they are involved in both, neuroprotection/neurorepair and neurodegeneration. There exist diverse and profound, regional and local, neuroglial changes in all involutive processes (physiological and pathological aging; neurodegenerative disorders, including Alzheimer¿s disease –AD-), but today, the exact meaning of such modifications (the modifications of the different neuroglial types, in time and place), is not well understood. In this review we consider the different neuroglial cells and their responses in order to understand the possible role they fulfill in pathogenesis, diagnosis and treatment (preventive or palliative) of AD. The existence of differentiated and/or concurrent pathogenic and neuro-protective/neuro-restorative astroglial and microglial responses is highlighted.Peer Reviewe

Postnatal development of astrocytic glia in the cerebellum of Cyprinus carpio.

Peer Reviewe