Effect of destruction of the brain serotoninergic system on alcohol intake by rats in the early stages of experimental alcoholism

1985 ◽  
Vol 99 (5) ◽  
pp. 604-606 ◽  
Author(s):  
V. N. Zhukov ◽  
A. I. Varkov ◽  
Yu. V. Burov
Keyword(s):  
Alcohol Intake ◽  
Serotoninergic System ◽  
Experimental Alcoholism ◽  
Early Stages ◽  
The Brain

scholarly journals Orexin receptor blockers: A tool for lowering alcohol intake and alcohol addictive behavior in the light of preclinical studies

2021 ◽  
Vol 75 (1) ◽  
pp. 959-969
Author(s):  
Kamila Czora-Poczwardowska ◽  
Radosław Kujawski ◽  
Julia Słyńko-Krzyżostaniak ◽  
Przemysław Ł. Mikołajczak ◽  
Michał Szulc
Keyword(s):  
Alcohol Intake ◽  
Selective Reduction ◽  
Optimization Methods ◽  
Sugar Solution ◽  
Behavioral Studies ◽  
Potential Efficacy ◽  
Bioactive Ligands ◽  
Receptor Blockers ◽  
Rats And Mice ◽  
The Brain

Abstract Alcohol use disorder (AUD) is a severe and globally widespread neurological and psychiatric problem. The treatment with currently used drugs often does not bring the expected effect. New optimization methods or directions in pharmacotherapy are still being sought. The group of bioactive ligands, targeted at neuropeptides called orexins (OXs) and their receptors (OXRs), affects a number of functions including ingestion, sleep-wake regulation, as well as the brain reward system which is the basis of addiction. The purpose of this paper is to systematize the knowledge in the field of preclinical behavioral studies on rodents (rats and mice) in several models of alcohol consumption using the OXRs antagonists. The results of the experiments indicated a potential efficacy of particular OXRs antagonists in the AUD treatment, especially those selectively blocking the OX1R. Among them, SB-334867 in the lowest effective dose of 3 mg/kg i.p. was most studied, as shown in the model of two-bottle choice using C57BL/6 mice. Moreover, this compound did not affect the reduction of cognitive functions. GSK1059865 was also involved in the selective reduction of ethanol intake, and simultaneously did not alter the consumption of sugar solution. The other group of selective OX2R antagonists, such as TCS-OX2-29 and LSN2424100, was less efficient. In summary, the OX1R antagonists proved to have the potential in AUD therapy, not only through the reduction of ethanol consumption but also in the treatment of coexisting behavioral and physiological disorders, such as insomnia and anxiety.

scholarly journals S-nitrosation of proteins relevant to Alzheimer’s disease during early stages of neurodegeneration

2016 ◽  
Vol 113 (15) ◽  
pp. 4152-4157 ◽  
Author(s):  
Uthpala Seneviratne ◽  
Alexi Nott ◽  
Vadiraja B. Bhat ◽  
Kodihalli C. Ravindra ◽  
John S. Wishnok ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Function ◽  
Amyloid Precursor Protein Processing ◽  
Amyloid Formation ◽  
Early Stages ◽  
Model Of Alzheimer’S Disease ◽  
Liquid Chromatography Tandem Mass ◽  
Cysteine Thiols ◽  
The Brain

Protein S-nitrosation (SNO-protein), the nitric oxide-mediated posttranslational modification of cysteine thiols, is an important regulatory mechanism of protein function in both physiological and pathological pathways. A key first step toward elucidating the mechanism by which S-nitrosation modulates a protein’s function is identification of the targeted cysteine residues. Here, we present a strategy for the simultaneous identification of SNO-cysteine sites and their cognate proteins to profile the brain of the CK-p25–inducible mouse model of Alzheimer’s disease-like neurodegeneration. The approach—SNOTRAP (SNO trapping by triaryl phosphine)—is a direct tagging strategy that uses phosphine-based chemical probes, allowing enrichment of SNO-peptides and their identification by liquid chromatography tandem mass spectrometry. SNOTRAP identified 313 endogenous SNO-sites in 251 proteins in the mouse brain, of which 135 SNO-proteins were detected only during neurodegeneration. S-nitrosation in the brain shows regional differences and becomes elevated during early stages of neurodegeneration in the CK-p25 mouse. The SNO-proteome during early neurodegeneration identified increased S-nitrosation of proteins important for synapse function, metabolism, and Alzheimer’s disease pathology. In the latter case, proteins related to amyloid precursor protein processing and secretion are S-nitrosated, correlating with increased amyloid formation. Sequence analysis of SNO-cysteine sites identified potential linear motifs that are altered under pathological conditions. Collectively, SNOTRAP is a direct tagging tool for global elucidation of the SNO-proteome, providing functional insights of endogenous SNO proteins in the brain and its dysregulation during neurodegeneration.

scholarly journals The Cerebellar Serotoninergic System and its Possible Involvement in Cerebellar Ataxia

1993 ◽  
Vol 20 (S3) ◽  
pp. S78-S82 ◽  
Author(s):  
P. Trouillas
Keyword(s):  
Cerebellar Ataxia ◽  
Purkinje Cells ◽  
Molecular Layer ◽  
Cortical Atrophy ◽  
Target Cells ◽  
Serotoninergic System ◽  
Synaptic Connections ◽  
Cerebellar Syndrome ◽  
Cerebellar Cortical Atrophy ◽  
The Brain

ABSTRACT:A review concerning the characteristics of the cerebellar serotoninergic system is presented. In rat, cat and oppossum, the perikarya of origin are located in the brain stem raphe nuclei and in other brainstem structures. The projections to the cerebellar layers and deep nuclei include synaptic connections, but also non synaptic terminals, espedaily in a diffuse cortical plexus. Serotoninergic receptors have been described: 5-HT1B in the molecular layer and 5-HT2 in the inferior olive. Serotonin exerts neurophysiological effects on several target cells, directly or indirectly, presynaptically or postsynaptically. A modulatory effect on Purkinje cells is well documented. In thiamine deprived animals, a specific serotoninergic cerebellar syndrome includes a selective degeneration of the serotoninergic cerebellar system, an increase of the 5-HIAA cerebellar values and an exaggerated serotoninergic turnover. In human here-doataxias (Friedreich’s ataxia and cerebellar cortical atrophy), serotoninergic disturbances have been observed in the CSF, including low 5-HIAA values and an increased serotoninergic turnover. Therapeutic results have been obtained with L-5-HTP, a precursor of serotonin, in several conditions presenting cerebellar ataxia. L-5-HTP resistance of olivo-pontocerebellar atrophies may be explained by the destruction of serotonin-sensitive target cells, especially Purkinje cells.

Influence of alcohol intake on cognitive functions of the brain

2010 ◽  
Vol 77 (3) ◽  
pp. 333-333
Author(s):  
Toshiharu Kurita ◽  
Mitsuru Kikuchi ◽  
Yoshio Minabe
Keyword(s):  
Cognitive Functions ◽  
Alcohol Intake ◽  
The Brain

scholarly journals Changes in neurotransmitter levels associated with the deficiency of some essential amino acids in the diet

1992 ◽  
Vol 68 (2) ◽  
pp. 409-420 ◽  
Author(s):  
José L. Venero ◽  
Antonio J. Herrera ◽  
Alberto Machado ◽  
Josefina Cano
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Substantia Nigra ◽  
Corpus Striatum ◽  
Essential Amino Acids ◽  
Serotoninergic System ◽  
Main Metabolite ◽  
Isoleucine Leucine ◽  
Low Protein ◽  
The Brain

The contents of dopamine (DA) and serotonin (5-HT) and their metabolites were measured in rat substantia nigra and corpus striatum following dietary changes, including restriction of protein content (low-protein diet; LPD) and the contents of several large neutral amino acids (isoleucine, leucine, methionine, phenylalanine, tryptophan and valine) for 25 d. The LPD produced an increase in the concentration of tyrosine (TYR) in the two regions of the brain studied. This effect was also observed with all amino acid deficiencies studied except for valine in the substantia nigra, tryptophan in the striatum and phenylalanine in both regions. Likewise, the concentration of 5-hydroxyindolacetic acid (5-HIAA), the main metabolite of 5-HT, increased in the substantia nigra but not in the striatum after LPD, as well as with all the amino acid deficiencies studied, with the exception of tryptophan deficiency. In this case there was a dramatic effect on all components of the serotoninergic system, with decreases in the concentration of tryptophan (TRP; precursor), 5-HT and 5-HIAA. This behaviour clearly shows an interrelationship between precursor (TRP) availability and 5-HT synthesis and metabolism. With valine deficiency, dopaminergic and serotoninergic systems demonstrated opposite effects in the substantia nigra and the corpus striatum, and the behaviour of the two monoamines was also opposite within each structure. The significance of these changes is discussed.

scholarly journals Toxic Models of Parkinson's Disease: History and Prospects

2021 ◽  
Vol 6 (3) ◽  
pp. 78-84
Author(s):  
D. S. Yaroshenko ◽  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Early Diagnosis ◽  
Brain Stem ◽  
Genetic Predisposition ◽  
Common Disease ◽  
Extrapyramidal System ◽  
Early Stages ◽  
The Brain

The review article presents data on the history of research of extrapyramidal system dysfunctions, modern ideas about the etiology and diagnosis of Parkinson's disease, as the most common disease of the group of extrapyramidal disorders. Currently, no concept of effective therapy for patients with extrapyramidal system dysfunction has been developed, but it has been proven that the probability of developing the disease largely depends on the genetic predisposition and the level of environmental pollution. In the early stages, the disease is slow and asymptomatic, but gradually more than half of patients with Parkinson's disease die, and others need outside care. According to experts, in the near future, Parkinson's disease will become a problem for a significant part of people, because today it affects more and more people of working age. Under such conditions, reliable and early diagnosis of the disease is of great importance, which guarantees timely and most effective treatment. Modern therapies fail to stop the progressive death of the dopaminergic neurons of the substantia nigra, but traditional treatment can achieve symptomatic relief. Currently, it is known that the probability of developing Parkinson's disease depends on the genetic predisposition and the level of man-made environmental stress. The researchers consider that the pathological development of Parkinson's disease in the brain begins in the lower structures of the brain stem with the involvement of the caudal-Rostral nuclei, as well as the involvement of the cortico-basal ganglia-cerebellar pathways. The pathological process affects the ascending pathways and gradually passes to the midbrain, directly to the black substance, spreads from there and weakens the mesocortex and neocortex. Injuries in the brain stem lead to disorganization of the cortico-basal ganglia and cerebellar pathways, followed by the formation of alternative pathways to compensate for the initial disorders in the early stages of the disease. In addition, in Parkinson's disease, intracellular Lewy bodies and neurites formed by the protein alpha-synuclein are created, which are found in the autopsy material of most patients. Poor results of diagnostic evaluation and treatment of Parkinson's disease are usually associated with a lack of understanding of the pathogenesis of Parkinson's disease. The study of the biological basis and pathogenesis of Parkinson's disease is an important task of a whole complex of scientific studies of extrapyramidal system dysfunction. Conclusion. The article discusses the creation of toxic models of Parkinson's disease in vivo and in vitro, which help to recreate the pathogenesis of the disease for early diagnosis and the development of new ways to treat neurodegenerative diseases. In toxic models of Parkinsonism, not only deficits of motor functions such as bradykinesia, tremor, and posture disorders are actively studied, but also non-motor symptoms such as sleep disorders, neuropsychiatric and cognitive abnormalities

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