- Actions of N-Acetylcysteine in the Central Nervous System: Implications for the Treatment of Neurodegenerative and 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 ◽  
...  

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.


2021 ◽  
Author(s):  
Mariana Acquarone ◽  
André Poleto ◽  
Ananda Perozzo ◽  
Patricia Gonçalves ◽  
Rogério Panizzutti ◽  
...  

Abstract Toxoplasma gondii is an opportunistic protozoan pathogen with a wide geographic distribution. The chronic phase of toxoplasmosis is often asymptomatic in humans and is characterized by tissue cysts throughout the central nervous system and muscle cells. T. gondii and other pathogens with tropism for the central nervous system are considered risk factors in the etiology of several neuropsychiatric disorders, such as schizophrenia and bipolar disorder, besides neurological diseases. Currently, it is known that cerebral toxoplasmosis increases dopamine levels in the brain and it is related to behavioral changes in animals and humans. Here we evaluate whether chronic T. gondii infection, using the cystogenic ME-49 strain, could induce behavioral alterations associated with neuropsychiatric disorders and glutamatergic neurotransmission dysfunction. We observed that the startle amplitude is reduced in the infected animals as well as glutamate and D-serine levels in prefrontal cortical and hippocampal tissue homogenates. Moreover, we did not detect alterations in social preference, spontaneous alternation, and tail suspension test despite severe motor impairment. Thus, we conclude that behavioral and cognitive aspects are maintained even though severe neural damage is observed by chronic infection of C57Bl/6 mice with the ME-49 strain.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mariana Acquarone ◽  
A. Poleto ◽  
A. F. Perozzo ◽  
P. F. R. Gonçalves ◽  
R. Panizzutti ◽  
...  

AbstractToxoplasma gondii is an opportunistic protozoan pathogen with a wide geographic distribution. The chronic phase of toxoplasmosis is often asymptomatic in humans and is characterized by tissue cysts throughout the central nervous system and muscle cells. T. gondii and other pathogens with tropism for the central nervous system are considered risk factors in the etiology of several neuropsychiatric disorders, such as schizophrenia and bipolar disorder, besides neurological diseases. Currently, it is known that cerebral toxoplasmosis increases dopamine levels in the brain and it is related to behavioral changes in animals and humans. Here we evaluate whether chronic T. gondii infection, using the cystogenic ME-49 strain, could induce behavioral alterations associated with neuropsychiatric disorders and glutamatergic neurotransmission dysfunction. We observed that the startle amplitude is reduced in the infected animals as well as glutamate and D-serine levels in prefrontal cortical and hippocampal tissue homogenates. Moreover, we did not detect alterations in social preference and spontaneous alternation despite severe motor impairment. Thus, we conclude that behavioral and cognitive aspects are maintained even though severe neural damage is observed by chronic infection of C57Bl/6 mice with the ME-49 strain.


Author(s):  
Gladys Harrison

With the advent of the space age and the need to determine the requirements for a space cabin atmosphere, oxygen effects came into increased importance, even though these effects have been the subject of continuous research for many years. In fact, Priestly initiated oxygen research when in 1775 he published his results of isolating oxygen and described the effects of breathing it on himself and two mice, the only creatures to have had the “privilege” of breathing this “pure air”.Early studies had demonstrated the central nervous system effects at pressures above one atmosphere. Light microscopy revealed extensive damage to the lungs at one atmosphere. These changes which included perivascular and peribronchial edema, focal hemorrhage, rupture of the alveolar septa, and widespread edema, resulted in death of the animal in less than one week. The severity of the symptoms differed between species and was age dependent, with young animals being more resistant.


Author(s):  
John L.Beggs ◽  
John D. Waggener ◽  
Wanda Miller ◽  
Jane Watkins

Studies using mesenteric and ear chamber preparations have shown that interendothelial junctions provide the route for neutrophil emigration during inflammation. The term emigration refers to the passage of white blood cells across the endothelium from the vascular lumen. Although the precise pathway of transendo- thelial emigration in the central nervous system (CNS) has not been resolved, the presence of different physiological and morphological (tight junctions) properties of CNS endothelium may dictate alternate emigration pathways.To study neutrophil emigration in the CNS, we induced meningitis in guinea pigs by intracisternal injection of E. coli bacteria.In this model, leptomeningeal inflammation is well developed by 3 hr. After 3 1/2 hr, animals were sacrificed by arterial perfusion with 3% phosphate buffered glutaraldehyde. Tissues from brain and spinal cord were post-fixed in 1% osmium tetroxide, dehydrated in alcohols and propylene oxide, and embedded in Epon. Thin serial sections were cut with diamond knives and examined in a Philips 300 electron microscope.


Author(s):  
Ezzatollah Keyhani

Acetylcholinesterase (EC 3.1.1.7) (ACHE) has been localized at cholinergic junctions both in the central nervous system and at the periphery and it functions in neurotransmission. ACHE was also found in other tissues without involvement in neurotransmission, but exhibiting the common property of transporting water and ions. This communication describes intracellular ACHE in mammalian bone marrow and its secretion into the extracellular medium.


Sign in / Sign up

Export Citation Format

Share Document