scholarly journals Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?

2021 ◽  
Vol 15 ◽  
Author(s):  
Francisney Pinto Nascimento ◽  
Sérgio José Macedo-Júnior ◽  
Fernanda Rocha Lapa-Costa ◽  
Fernando Cezar-dos-Santos ◽  
Adair R. S. Santos
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Psychiatric Disorders ◽  
Therapeutic Potential ◽  
Purinergic Signaling ◽  
Neural Regeneration ◽  
Parasympathetic Nerves ◽  
Mediated Effects ◽  
Naturally Occurring ◽  
The Central Nervous System

Since the 1970s, when ATP was identified as a co-transmitter in sympathetic and parasympathetic nerves, it and its active metabolite adenosine have been considered relevant signaling molecules in biological and pathological processes in the central nervous system (CNS). Meanwhile, inosine, a naturally occurring purine nucleoside formed by adenosine breakdown, was considered an inert adenosine metabolite and remained a neglected actor on the purinergic signaling scene in the CNS. However, this scenario began to change in the 1980s. In the last four decades, an extensive group of shreds of evidence has supported the importance of mediated effects by inosine in the CNS. Also, inosine was identified as a natural trigger of adenosine receptors. This evidence has shed light on the therapeutic potential of inosine on disease processes involved in neurological and psychiatric disorders. Here, we highlight the clinical and preclinical studies investigating the involvement of inosine in chronic pain, schizophrenia, epilepsy, depression, anxiety, and in neural regeneration and neurodegenerative diseases, such as Parkinson and Alzheimer. Thus, we hope that this review will strengthen the knowledge and stimulate more studies about the effects promoted by inosine in neurological and psychiatric disorders.

RAS in the Central Nervous System: Potential Role in Neuropsychiatric Disorders

2018 ◽  
Vol 25 (28) ◽  
pp. 3333-3352 ◽  
Author(s):  
Natalia Pessoa Rocha ◽  
Ana Cristina Simoes e Silva ◽  
Thiago Ruiz Rodrigues Prestes ◽  
Victor Feracin ◽  
Caroline Amaral Machado ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neuropsychiatric Disorders ◽  
Extensive Literature ◽  
Ang Ii ◽  
Mas Receptor ◽  
The Central Nervous System ◽  
The Brain

Background: The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. Objective: We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders for the modulation of RAS. Method: We carried out an extensive literature search in PubMed central. Results: Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Conclusion: Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.

Neurochemical Systems in the Central Nervous System

2013 ◽  
pp. 12-26
Author(s):  
Ariel Y. Deutch ◽  
Robert H. Roth
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Psychiatric Disorders ◽  
Neurotrophic Factors ◽  
Drugs Of Abuse ◽  
Large Majority ◽  
System P ◽  
Target Neuron ◽  
The Central Nervous System ◽  
The Brain

Chapter 2 describes the neurochemical organization of the brain. It summarizes the diverse types of molecules that neurons in the brain use as neurotransmitters and neurotrophic factors, and how these molecules are synthesized and metabolized. The chapter also presents the array of receptor proteins through which these molecules regulate target neuron functioning and the reuptake proteins that generally terminate the neurotransmitter signal. Today a large majority of all drugs used to treat psychiatric disorders, as well as most drugs of abuse, still have as their initial targets proteins involved directly in neurotransmitter function.

Biological correlates of personality: considerations on the possible usefulness of central nervous system peripheral markers

1993 ◽  
Vol 8 (3) ◽  
pp. 115-124 ◽  
Author(s):  
P Castrogiovanni ◽  
F Pieraccini ◽  
I Maremmani ◽  
D Marazziti
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Psychiatric Disorders ◽  
Human Studies ◽  
Biological Research ◽  
The Central Nervous System ◽  
Methodological Problems ◽  
Biological Substrates ◽  
Peripheral Markers ◽  
Made In

SummaryAlthough a great deal of biological research has been carried out on several psychiatric disorders, it is disappointing to see how little progress has been made in the field of the biology of personality. The authors underline the methodological problems that arise in the investigation of biological substrates of human personality and review both currently available and putative peripheral markers of the central nervous system that might be used in further human studies.

scholarly journals Mitochondria and the central nervous system: searching for a pathophysiological basis of psychiatric disorders

2014 ◽  
Vol 36 (2) ◽  
pp. 156-167 ◽  
Author(s):  
Emilio L. Streck ◽  
Cinara L. Gonçalves ◽  
Camila B. Furlanetto ◽  
Giselli Scaini ◽  
Felipe Dal-Pizzol ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Psychiatric Disorders ◽  
The Central Nervous System

Role of the glucose-dependent insulinotropic polypeptide and its receptor in the central nervous system: therapeutic potential in neurological diseases

2010 ◽  
Vol 21 (5-6) ◽  
pp. 394-408 ◽  
Author(s):  
Cláudia P. Figueiredo ◽  
Fabrício A. Pamplona ◽  
Tânia L. Mazzuco ◽  
Aderbal S. Aguiar ◽  
Roger Walz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
The Central Nervous System

scholarly journals Dexamethasone promotes IL-4-induced alternative activation at PPARγ point, instead of upstream STAT6 in BV2 microglial cells

2020 ◽  
Author(s):  
Zongfeng Chen ◽  
Liang Zhang ◽  
Xin Xue ◽  
Peng Liu ◽  
Xiang Yin ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Therapeutic Potential ◽  
Polarization State ◽  
Microglial Cells ◽  
Alternative Activation ◽  
Peroxisome Proliferator ◽  
Activation Markers ◽  
Arginase 1 ◽  
The Central Nervous System

Abstract Background Microglia are innate immune effector cells in the central nervous system and play an extremely important role in the physiological processes of the central nervous system. When microglia are activated, there are two polarization states, M1 and M2 phenotype. Dexamethasone is a glucocorticoid widely used in clinical practice, which pharmacological effects are mainly anti-inflammatory, anti-toxic. However, whether Dexamethasone affects polarization state of microglia is unknown. In this study, we investigate the effect of Dexamethasone on IL-4-induced alternative activation in murine BV-2 microglial cells. Methods BV-2 cells were incubated with Dexamethasone alone, IL-4 alone, or the combination of Dexamethasone and IL-4. Western blot and immunofluorescence were performed to detect protein levels of alternative activation markers arginase 1 (Arg1), found in inflammatory zone 1 (FIZZ1). Moreover, we investigated the effects of Dexamethasone on IL-4 induced activation of signal transducer and activators of transcription 6 (STAT6) and peroxisome proliferator-activated receptor-gamma (PPARγ). Results Dexamethasone promoted IL-4 induced microglia alternative activation by increasing the expression of Arg1 and FIZZ1. Dexamethasone also enhanced the expression of PPARγ. These effects were reversed by RU486 (a Dexamethasone antagonist). Further, the effects of Dexamethasone and IL-4 on Arg1 and FIZZ1 were blocked by the application of GW9662 (a PPARγ antagonist). Conclusions Our studies confirm that Dexamethasone promotes IL-4 induced alternative activation via STAT6/PPARγ signaling pathways in microglia. At the same time, it was confirmed that Dexamethasone acts on PPARγ instead of STAT6. These findings support that Dexamethasone has a therapeutic potential for neuroinflammatory diseases via alternative activation.

Immune Mechanisms Affecting the Functioning of the Central Nervous System (CNS)

2018 ◽  
pp. 47-64
Author(s):  
Moises E. Bauer ◽  
Natália P. Rocha ◽  
Wilson Savino ◽  
Antonio L. Teixeira
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Psychiatric Disorders ◽  
Hippocampal Neurogenesis ◽  
Behavioral Symptoms ◽  
Immune Mechanisms ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Impaired Cognition

This chapter presents an overview of the immune mechanisms affecting the functioning of the central nervous system (CNS). The cross-talk between the immune system and the CNS is established by three independent pathways: the humoral, neural, and cellular (leukocyte) routes. Of note, increased circulating pro-inflammatory cytokines and concomitant activation of brain-resident microglia can lead to impaired cognition and depressive behavioral symptoms. The activated microglia phenotype has been associated with neuroinflammation reported in neurodegenerative and psychiatric disorders. This chapter also reviews novel physiological roles for adaptive immunity (especially T cells) during health and disease. T cells support hippocampal neurogenesis, cognition, mood, resilience to stress, and are protective against the development of psychiatric disorders.

scholarly journals Social Experience-Dependent Myelination: An Implication for Psychiatric Disorders

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Michihiro Toritsuka ◽  
Manabu Makinodan ◽  
Toshifumi Kishimoto
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Psychiatric Disorders ◽  
Conduction Velocity ◽  
Neuronal Activity ◽  
Social Experience ◽  
Multiple Factors ◽  
The Central Nervous System ◽  
Extracellular Molecules ◽  
Activity Dependent

Myelination is one of the strategies to promote the conduction velocity of axons in order to adjust to evolving environment in vertebrates. It has been shown that myelin formation depends on genetic programing and experience, including multiple factors, intracellular and extracellular molecules, and neuronal activities. Recently, accumulating studies have shown that myelination in the central nervous system changes more dynamically in response to neuronal activities and experience than expected. Among experiences, social experience-dependent myelination draws attention as one of the critical pathobiologies of psychiatric disorders. In this review, we summarize the mechanisms of neuronal activity-dependent and social experience-dependent myelination and discuss the contribution of social experience-dependent myelination to the pathology of psychiatric disorders.

scholarly journals The orexins/hypocretins: hypothalamic peptides linked to sleep and appetite

2002 ◽  
Vol 32 (6) ◽  
pp. 955-958 ◽  
Author(s):  
SHAHRAD TAHERI ◽  
SEPEHR HAFIZI
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Sleep Disorder ◽  
Psychiatric Disorders ◽  
Lateral Hypothalamus ◽  
Scientific Knowledge ◽  
State Of The Art ◽  
Molecular Techniques ◽  
Medical Community ◽  
The Central Nervous System

The orexins/hypocretins are novel neuropeptides synthesized by neurons whose cell bodies are located in the lateral hypothalamus. Although these neurons are few in number, they send projections widely throughout the central nervous system (Kilduff & Peyron, 2000). There has been great excitement about the orexins/hypocretins from both the scientific and medical community. These peptides are remarkable in that they were discovered using state-of-the-art molecular techniques before their physiological actions were studied. Furthermore, there has been an exponential progress in our scientific knowledge of these peptides culminating in the orexins/hypocretins being linked to the sleep disorder, narcolepsy. With the importance of the orexins/hypocretins in sleep and arousal being increasingly recognized, it is likely that these peptides are altered by or contribute to several medical and psychiatric disorders.

Sign in / Sign up

Export Citation Format

Share Document