scholarly journals Genetic approaches to the investigation of serotonergic neuron functions in animals

2019 ◽  
Vol 23 (4) ◽  
pp. 448-455
Author(s):  
U. S. Drozd ◽  
E. V. Shaburova ◽  
N. N. Dygalo

The serotonergic system is one of the most important neurotransmitter systems that take part in the regulation of vital CNS functions. The understanding of its mechanisms will help scientists create new therapeutic approaches to the treatment of mental and neurodegenerative diseases and find out how this neurotransmitter system interacts with other parts of the brain and regulates their activity. Since the serotonergic system anatomy and functionality are heterogeneous and complex, the best tools for studying them are based on manipulation of individual types of neurons without affecting neurons of other neurotransmitter systems. The selective cell control is possible due to the genetic determinism of their functions. Proteins that determine the uniqueness of the cell type are expressed under the regulation of cell-specific promoters. By using promoters that are specific for genes of the serotonin system, one can control the expression of a gene of interest in serotonergic neurons. Here we review approaches based on such promoters. The genetic models to be discussed in the article have already shed the light on the role of the serotonergic system in modulating behavior and processing sensory information. In particular, genetic knockouts of serotonin genes sert, pet1, and tph2 promoted the determination of their contribution to the development and functioning of the brain. In addition, the review describes inducible models that allow gene expression to be controlled at various developmental stages. Finally, the application of these genetic approaches in optogenetics and chemogenetics provided a new resource for studying the functions, discharge activity, and signal transduction of serotonergic neurons. Nevertheless, the advantages and limitations of the discussed genetic approaches should be taken into consideration in the course of creating models of pathological conditions and developing pharmacological treatments for their correction.

1993 ◽  
Vol 5 (4) ◽  
pp. 71-75
Author(s):  
C. Aaldijk ◽  
W.W. Van Den Broek ◽  
R.C. Van Der Mast

SummaryIn this review the most important hypotheses for the occurrence of the clinical picture of hepatic encephalopathy are discussed. As possible pathogenetic mechanisms are raised: dysfunction of the serotonergic system due to an increased tryptophan uptake in the brain, an elevated intracerebral ammoniac concentration and glutamine synthesis, and a heightened intracerebral GABA-activity.The dysregulation of the serotonergic system as a consequence of the increased intracerebral tryptophan uptake is described as one of the most important pathogenetic mechanisms. The elevated intracerebral ammoniac concentration and the elevated intracerebral glutamine synthesis play in this a facilitating role. The similarity in symptomatology of the clinical picture of HE and the serotonergic syndrome support this hypothesis. Due to contradictory research findings the role of the GABA-ergic system and the occurrence of HE remains unclear.


2014 ◽  
Vol 1 (3) ◽  
pp. 168-173
Author(s):  
Ivana Timotijevic ◽  
Mirjana Todorovic ◽  
Katarina Crnic ◽  
Srdjan Markovic ◽  
Dragana Kastratovic

2019 ◽  
Vol 20 (12) ◽  
pp. 2982 ◽  
Author(s):  
Gil Yong Park ◽  
Angelo Jamerlan ◽  
Kyu Hwan Shim ◽  
Seong Soo A. An

Transthyretin (TTR) is a thyroid hormone-binding protein which transports thyroxine from the bloodstream to the brain. The structural stability of TTR in tetrameric form is crucial for maintaining its original functions in blood or cerebrospinal fluid (CSF). The altered structure of TTR due to genetic mutations or its deposits due to aggregation could cause several deadly diseases such as cardiomyopathy and neuropathy in autonomic, motor, and sensory systems. The early diagnoses for hereditary amyloid TTR with cardiomyopathy (ATTR-CM) and wild-type amyloid TTR (ATTRwt) amyloidosis, which result from amyloid TTR (ATTR) deposition, are difficult to distinguish due to the close similarities of symptoms. Thus, many researchers investigated the role of ATTR as a biomarker, especially its potential for differential diagnosis due to its varying pathogenic involvement in hereditary ATTR-CM and ATTRwt amyloidosis. As a result, the detection of ATTR became valuable in the diagnosis and determination of the best course of treatment for ATTR amyloidoses. Assessing the extent of ATTR deposition and genetic analysis could help in determining disease progression, and thus survival rate could be improved following the determination of the appropriate course of treatment for the patient. Here, the perspectives of ATTR in various diseases were presented.


2020 ◽  
Author(s):  
Lauri Nummenmaa ◽  
Kerttu Seppälä ◽  
Vesa Putkinen

Emotions modulate behavioural priorities at the central and peripheral nervous system. Understanding emotions from the perspective of specific neurotransmitter systems is critical, because the central role of affect in multiple psychopathologies, and the role of specific neuroreceptor systems as corresponding drug targets. Here we provide an integrative overview of molecular imaging studies that have targeted the human emotion circuit at the level of specific neuroreceptors and transmitters. We focus specifically on opioid, dopamine and serotonin system given their key role in modulating motivation and emotions, and discuss how they contribute to both healthy and pathological emotions.


2021 ◽  
Vol 12 ◽  
Author(s):  
Faranak Vahid-Ansari ◽  
Paul R. Albert

Serotonin is a key neurotransmitter that is implicated in a wide variety of behavioral and cognitive phenotypes. Originating in the raphe nuclei, 5-HT neurons project widely to innervate many brain regions implicated in the functions. During the development of the brain, as serotonin axons project and innervate brain regions, there is evidence that 5-HT plays key roles in wiring the developing brain, both by modulating 5-HT innervation and by influencing synaptic organization within corticolimbic structures. These actions are mediated by 14 different 5-HT receptors, with region- and cell-specific patterns of expression. More recently, the role of the 5-HT system in synaptic re-organization during adulthood has been suggested. The 5-HT neurons have the unusual capacity to regrow and reinnervate brain regions following insults such as brain injury, chronic stress, or altered development that result in disconnection of the 5-HT system and often cause depression, anxiety, and cognitive impairment. Chronic treatment with antidepressants that amplify 5-HT action, such as selective serotonin reuptake inhibitors (SSRIs), appears to accelerate the rewiring of the 5-HT system by mechanisms that may be critical to the behavioral and cognitive improvements induced in these models. In this review, we survey the possible 5-HT receptor mechanisms that could mediate 5-HT rewiring and assess the evidence that 5-HT-mediated brain rewiring is impacting recovery from mental illness. By amplifying 5-HT-induced rewiring processes using SSRIs and selective 5-HT agonists, more rapid and effective treatments for injury-induced mental illness or cognitive impairment may be achieved.


1980 ◽  
Vol 20 (6) ◽  
pp. 1893-1898 ◽  
Author(s):  
Carmela F DE GAETANI ◽  
Rosanna POGGIOLI ◽  
Paola FERRARI ◽  
B. MESS ◽  
G. P. TRENTINI

2021 ◽  
Vol 22 (18) ◽  
pp. 9806
Author(s):  
Martyna Bayassi-Jakowicka ◽  
Grazyna Lietzau ◽  
Ewelina Czuba ◽  
Aleksandra Steliga ◽  
Monika Waśkow ◽  
...  

A growing body of evidence suggests that nucleus accumbens (NAc) plays a significant role not only in the physiological processes associated with reward and satisfaction but also in many diseases of the central nervous system. Summary of the current state of knowledge on the morphological and functional basis of such a diverse function of this structure may be a good starting point for further basic and clinical research. The NAc is a part of the brain reward system (BRS) characterized by multilevel organization, extensive connections, and several neurotransmitter systems. The unique role of NAc in the BRS is a result of: (1) hierarchical connections with the other brain areas, (2) a well-developed morphological and functional plasticity regulating short- and long-term synaptic potentiation and signalling pathways, (3) cooperation among several neurotransmitter systems, and (4) a supportive role of neuroglia involved in both physiological and pathological processes. Understanding the complex function of NAc is possible by combining the results of morphological studies with molecular, genetic, and behavioral data. In this review, we present the current views on the NAc function in physiological conditions, emphasizing the role of its connections, neuroplasticity processes, and neurotransmitter systems.


CNS Spectrums ◽  
1998 ◽  
Vol 3 (6) ◽  
pp. 38-47 ◽  
Author(s):  
Concetta M. DeCaria ◽  
Tomer Begaz ◽  
Eric Hollander

AbstractResearch on pathological gambling has begun to demonstrate the significant pathophysiologic role of several neurotransmitter systems in this disorder. Challenge studies with various pharmacologic agents have suggested the importance of potential dysregulation of the serotonergic system in pathological gambling, as this system is linked to dysfunction in behavioral initiation and inhibition. In addition, the noradrenergic system has been associated with mediation of arousal, increases of which are manifested by pathological gamblers. The interactions between these and other neurotransmitter systems, as well as the similarities between pathological gambling and other behavioral disorders, may provide important clues for pharmacologic intervention.


1995 ◽  
Vol 73 (2) ◽  
pp. 246-254 ◽  
Author(s):  
Chantal Bard ◽  
Michelle Fleury ◽  
Normand Teasdale ◽  
Jacques Paillard ◽  
Vincent Nougier

The absence of muscular proprioception, whether at a segmental or at a central level, impairs performance in several ways. The contribution of proprioception to movement control and learning is not easily dissociated from that of other sources of sensory information (e.g., vision). Therefore, the rare clinical cases of extensive neuropathy, depriving the brain massively and permanently of its presumed main sources of dynamogenic information from skin and muscles, are of very special interest. Two such patients and controls were tested in experiments investigating (i) force production, (ii) amplitude coding, (iii) spatial reference frames in pointing, and (iv) prismatic adaptation. Overall, our results highlight the key role of proprioceptive afferents for calibrating the spatial motor frame of reference, and the powerful substitutive properties of the central nervous system.Key words: proprioception, deafferentation, space calibration, motor control.


2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Behdad Tahayori ◽  
David M. Koceja

Part of the development and maturation of the central nervous system (CNS) occurs through interactions with the environment. Through physical activities and interactions with the world, an animal receives considerable sensory information from various sources. These sources can be internally (proprioceptive) or externally (such as touch and pressure) generated senses. Ample evidence exists to demonstrate that the sensory information originating from large diameter afferents (Ia fibers) have an important role in inducing essential functional and morphological changes for the maturation of both the brain and the spinal cord. The Ia fibers transmit sensory information generated by muscle activity and movement. Such use or activity-dependent plastic changes occur throughout life and are one reason for the ability to acquire new skills and learn new movements. However, the extent and particularly the mechanisms of activity-dependent changes are markedly different between a developing nervous system and a mature nervous system. Understanding these mechanisms is an important step to develop strategies for regaining motor function after different injuries to the CNS. Plastic changes induced by activity occur both in the brain and spinal cord. This paper reviews the activity-dependent changes in the spinal cord neural circuits during both the developmental stages of the CNS and in adulthood.


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