Current Neuropharmacology

ISSN: 1570-159X

Current Neuropharmacology
Volume 8, Number 2, June 2010

Contents

Aquaporins and Nervous System: from Bench to Bedside
Guest Editors: Rita Rezzani and Luigi F. Rodella


Editorial Pp. 83


Aquaporins and Glia Pp. 84-91
Albertini Roberta and Bianchi Rossella
[Abstract] [Purchase Article]


Aquaporin and Blood Brain Barrier Pp. 92-96
Bonomini Francesca and Rita Rezzani
[Abstract] [Purchase Article]


Aquaporin Biology and Nervous System Pp. 97-104
Buffoli Barbara
[Abstract] [Purchase Article]


Aquaporin and Vascular Diseases Pp. 105-111
Carla Loreto and Ester Reggio
[Abstract] [Purchase Article]


Aquaporins and Neurodegenerative Diseases Pp. 112-121
Eleonora Foglio and Rodella Luigi Fabrizio
[Abstract] [Purchase Article]


Aquaporins in Sensory and Pain Transmission Pp. 122-127
Elisa Borsani
[Abstract] [Purchase Article]


General Articles


Ischemia-Reperfusion Injury of the Cochlea: Pharmacological Strategies for Cochlear Protection and Implications of Glutamate and Reactive Oxygen Species Pp. 128-134
Keiji Tabuchi, Bungo Nishimura, Shuho Tanaka, Kentaro Hayashi, Yuki Hirose and Akira Hara
[Abstract] [Purchase Article]


Clinical and Pharmacological Aspects of Inflammatory Demyelinating Diseases in Childhood: An Update Pp. 135-148
Alberto Spalice, Pasquale Parisi, Laura Papetti, Francesco Nicita, Fabiana Ursitti, Francesca Del Balzo, Enrico Properzi, Alberto Verrotti, Martino Ruggieri and Paola Iannetti
[Abstract] [Purchase Article]


Winning a Won Game: Caffeine Panacea for Obesity Syndemic Pp. 149-160
M. Myslobodsky and A. Eldan
[Abstract] [Purchase Article]




Abstracts

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Editorial: Aquaporins and Nervous System: from Bench to Bedside

Water is the single most abundant substance in cells and organisms and is an important molecule involved in several biochemical processes present in living cells. In humans 60-70% of body weight is water which equilibrates across the lipid bilayer in cell membranes. Forty years ago, a small number of scientists argued that specialized water-selective pores are necessary to explain the high water permeability of red blood cells and renal tubules. Therefore, the molecular identification of a 28 kDa integral membrane protein in these cells has characterized a new stream of research. Aquaporins (AQPs) are membrane proteins that transport water and, in some cases, also small solutes such as glycerol and urea. Each subtype has its own cellular distribution and distinct regulatory mechanisms of their expression. Their classical role in facilitating trans-epithelial fluid transport is well understood, as in the urinary concentrating mechanism and gland fluid secretion, while the molecular mechanisms to regulate water permeability in the nervous system are still unclear. Maintenance of the ionic and osmotic composition and volume of interstitial, glial and neuronal compartments within the nervous system is essential for normal function. Small changes in intracellular or extracellular ion or solute composition can dramatically modify bi-directional water pathway between the brain and blood vessels and alter cerebrospinal fluid formation, neural signal transduction and information processing. To date, only some AQP isoforms (AQP1, 3, 4, 5, 8, 9) have been reported in the central nervous system being identified in choroidal cells (AQP1), astrocytes (AQP1, 3, 4, 5, 8, 9), oligodendrocytes (AQP8), neurons (AQP1, 5, 8), tanycytes (AQP9) and ependymal cells (AQP1, 4, 9). In contrast to numerous studies of AQP localization and function in the central nervous system, little information is available on the expression and function of AQPs in peripheral nervous system. This issue includes six review articles in which the authors report and explore the recent findings about the involvement of AQPs both in peripheral and central nervous system.

The paper by B. Buffoli summarizes the data about the structure, regulation and function of AQPs, giving more importance to their involvement in the nervous system and underlying the development of new methods for diagnosis and therapy diseases.

The review of R. Albertini and R. Bianchi is focused on the different isoforms of AQP protein that have been identified in glial cells in central and peripheral nervous system and in reactive microglial. The chapter supports the idea that AQPs are involved in water homeostasis during different glial cell functions, such as differentiation, metabolism and excitability of neurons.

F. Bonomini and R. Rezzani emphasize the role of some AQPs present in glial cells in the maintenance or/and in the regulatory mechanisms of blood brain barrier.

On the basis of the role of AQPs in brain edema, a personal account of the role of AQPs is then presented by C. Loreto and E. Reggio, who summarized the implication of different isoforms of these proteins in relation with vascular diseases and nervous system.

In the literature, there is a lot of evidence that indicates a correlation between the expression of AQPs and the development of neurodegenerative diseases in which preservation of brain homeostasis is at risk. The review of E. Foglio and L.F. Rodella was to consider this topic concentrating on some neurodegenerative diseases, such as Neuromyielitis Optica, Alzheimer’s Diseases, Parkinson’s Diseases, Amyotrophic lateral sclerosis, Transmissible Spongiform Encephalopathies.

Recent evidence suggests a novel role of AQPs in pain transmission both in the central and peripheral nervous system. In this issue, E. Borsani reports the modulation of AQPs both in inflammatory and neuropathic pain considering different animal models and knock-out animals.

In the future, the numerous ongoing studies will certainly reveal other multifunctional roles of these proteins in humans. These roles might be exploited clinically by the development of drugs to alter AQP expression or function that could serve in the treatment of different diseases associated to peripheral and central nervous system.




Rita Rezzani
Chair of Division of Human Anatomy,
Department of Biomedical Sciences
and Biotechnologies,
University of Brescia,
V.le Europa 11, 25123
Brescia, Italy
Tel: +39 030 3717483
Fax: +39 030 3717486
E-mail: rezzani@med.unibs.it


Luigi F. Rodella
Division of Human Anatomy,
Department of Biomedical Sciences
and Biotechnologies,
University of Brescia,
V.le Europa 11, 25123
Brescia, Italy
Tel: +39 030 3717485
Fax: +39 0303717486
E-mail: rodella@med.unibs.it


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Aquaporins and Glia
Albertini Roberta and Bianchi Rossella

Glial cells coordinate the differentiation, metabolism, and excitability of neurons; they modulate synaptic transmission and integrate signals emanating from neurons and other glial cells. Several evidences underlying the relation between these pathways and the regulatory mechanisms of ion concentration, supporting the role of Aquaporins (AQPs) in these processes.

The goal of this review is to summarize the localization of different isoforms of AQPs in relation to glial cells both in central and peripheral nervous system, underlying AQP involvement in physiological and in pathophysiological conditions such as brain edema, glioma and epilepsy.


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Aquaporin and Blood Brain Barrier
Bonomini Francesca and Rita Rezzani

Large water fluxes continuously take place between the different compartments of the brain as well as between the brain parenchyma and the blood or cerebrospinal fluid.

Disturbances in this well-regulated water homeostasis may have deleterious effects on brain function and may be fatal in cases where water accumulates in the brain following pathologies such as ischemia, haemorrhage, or brain trauma.

The molecular pathways by which water molecules cross the blood brain barrier are not well-understood, although the discovery of Aquaporin 4 (AQP4) in the brain improved the understanding of some of these transport processes, particularly under pathological conditions.


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Aquaporin Biology and Nervous System
Buffoli Barbara

Our understanding of the movement of water through cell membranes has been greatly advanced by the discovery of a family of water-specific, membrane-channel proteins: the Aquaporins (AQPs). These proteins are present in organisms at all levels of life, and their unique permeability characteristics and distribution in numerous tissues indicate diverse roles in the regulation of water homeostasis.

Phenotype analysis of AQP knock-out mice has confirmed the predicted role of AQPs in osmotically driven transepithelial fluid transport, as occurs in the urinary concentrating mechanism and glandular fluid secretion. Regarding their expression in nervous system, there are evidences suggesting that AQPs are differentially expressed in the peripheral versus central nervous system and that channel-mediated water transport mechanisms may be involved in cerebrospinal fluid formation, neuronal signal transduction and information processing.

Moreover, a number of recent studies have revealed the importance of mammalian AQPs in both physiological and pathophysiological mechanisms and have suggested that pharmacological modulation of AQP expression and activity may provide new tools for the treatment of variety of human disorders in which water and small solute transport may be involved.

For all the AQPs, new contributions to physiological functions are likely to be discovered with ongoing work in this rapidly expanding field of research.


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Aquaporin and Vascular Diseases
Carla Loreto and Ester Reggio

Aquaporins (AQP) are family of water channels found in several epithelial and endothelial cells, whose recent identification has provided insights into water transport in several tissues, including the central nervous system (CNS). Since brain edema continues to be the main cause of death from several CNS diseases, such as stroke, much of the interest in AQPs and their functional contribution to the water balance is due to their possible role in clearing edema water from the brain and in managing hydrocephalus and benign intracranial hypertension, suggesting that they could be targets for future treatments of various brain conditions, particularly vascular diseases. AQPs also seem to be involved in cell migration, and a mechanism of AQP-facilitated cell migration has been proposed where local osmotic gradients created at the tip of the lamellipodium drive water influx, facilitating lamellipodial extension and cell migration. AQP-facilitated cell migration was also detected in tumour cells, suggesting that it may have an important role in tumour angiogenesis and spread, and accounting for AQP expression in many tumour cell types and for correlations found between AQP expression and tumour stage in some tumours.


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Aquaporins and Neurodegenerative Diseases
Eleonora Foglio and Rodella Luigi Fabrizio

Aquaporins (AQPs) are a family of widely distributed membrane-inserted water channel proteins providing a pathway for osmotically-driven water, glycerol, urea or ions transport through cell membranes and mechanisms to control particular aspects of homeostasis. Beside their physiological expression patterns in Central Nervous System (CNS), it is conceivable that AQPs are also abnormally expressed in some pathological conditions interesting CNS (e.g. neurodegenerative diseases) in which preservation of brain homeostasis is at risk.

The purpose of this review was to take in consideration those neurodegenerative diseases in whose pathogenetic processes it was possible to hypothesize some alterations in CNS AQPs expression or modulation leading to damages of brain water homeostasis.


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Aquaporins in Sensory and Pain Transmission
Elisa Borsani

Recent data suggest a possible involvement of Aquaporins (AQPs) in pain transmission. AQPs are small membrane channel proteins involved in osmoregulation and, to date, AQP1, AQP2, AQP3, AQP4, AQP5, AQP8 and AQP9 have been found in the nervous system. Nevertheless only AQP1, AQP2 and AQP4 seem to be involved in nociception.

In this review, direct and indirect evidences of the role of AQPs in pain processing will be reported.


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Ischemia-Reperfusion Injury of the Cochlea: Pharmacological Strategies for Cochlear Protection and Implications of Glutamate and Reactive Oxygen Species
Keiji Tabuchi, Bungo Nishimura, Shuho Tanaka, Kentaro Hayashi, Yuki Hirose and Akira Hara

A large amount of energy produced by active aerobic metabolism is necessary for the cochlea to maintain its function. This makes the cochlea vulnerable to blockade of cochlear blood flow and interruption of the oxygen supply. Although certain forms of human idiopathic sudden sensorineural hearing loss reportedly arise from ischemic injury, the pathological mechanism of cochlear ischemia-reperfusion injury has not been fully elucidated. Recent animal studies have shed light on the mechanisms of cochlear ischemia-reperfusion injury. It will help in the understanding of the pathology of cochlear ischemia-reperfusion injury to classify this injury into ischemic injury and reperfusion injury. Excitotoxicity, mainly observed during the ischemic period, aggravates the injury of primary auditory neurons. On the other hand, oxidative damage induced by hydroxyl radicals and nitric oxide enhances cochlear reperfusion injury. This article briefly summarizes the generation mechanisms of cochlear ischemia-reperfusion injury and potential therapeutic targets that could be developed for the effective management of this injury type.


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Clinical and Pharmacological Aspects of Inflammatory Demyelinating Diseases in Childhood: An Update
Alberto Spalice, Pasquale Parisi, Laura Papetti, Francesco Nicita, Fabiana Ursitti, Francesca Del Balzo, Enrico Properzi, Alberto Verrotti, Martino Ruggieri and Paola Iannetti

Inflammatory demyelinating diseases comprise a spectrum of disorders affecting the myelin of the central and peripheral nervous system. These diseases can usually be differentiated on the basis of clinical, radiological, laboratory and pathological findings.

Recent studies have contributed to current awareness that inflammatory demyelinating diseases are not restricted to the adult age group, but are more common in pediatric age than previously believed. Some of pediatric inflammatory demyelinating diseases carry an unfavorable long-term prognosis but appropriate treatments can improve the outcome. The possibility of physical and cognitive disability resulting from these diseases, highlights the urgent need for therapeutic strategies for neurorehabilitation, neuroregeneration, and neurorepair.

This review discusses characteristics of primary demyelinating diseases more frequently observed in childhood, focusing on epidemiology, clinical aspects and treatments.


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Winning a Won Game: Caffeine Panacea for Obesity Syndemic
M. Myslobodsky and A. Eldan

Over the past decades, chronic sleep reduction and a concurrent development of obesity have been recognized as a common problem in the industrialized world. Among its numerous untoward effects, there is a possibility that insomnia is also a major contributor to obesity. This attribution poses a problem for caffeine, an inexpensive, “natural” agent that is purported to improve a number of conditions and is often indicated in a long-term pharmacotherapy in the context of weight management. The present study used the “common target” approach by exploring the tentative shared molecular networks of insomnia and adiposity. It discusses caffeine targets beyond those associated with adenosine signaling machinery, phosphodiesterases, and calcium release channels. Here, we provide a view suggesting that caffeine could exert some of its effects by acting on several signaling complexes composed of HIF-1α/VEGF/IL-8 along with NO, TNF-α, IL1, and GHRH, among others. Although the relevance of these targets to the reported therapeutic effects of caffeine has remained difficult to assess, the utilization of caffeine efficacies and potencies recommend its repurposing for development of novel therapeutic approaches. Among indications mentioned, are neuroprotective, nootropic, antioxidant, proliferative, anti-fibrotic, and anti-angiogenic that appear under a variety of dissimilar diagnostic labels comorbid with obesity. In the absence of safe and efficacious antiobesity agents, caffeine remains an attractive adjuvant.