Dopamine in Health and Disease 2.0

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 29158

Special Issue Editor


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Guest Editor
Department of Biology, Faculty of Science, University of Ottawa, Ottawa, ON K1N 6N5, Canada
Interests: brain development and regeneration; development of dopamine and GABA neurons; control of gene expression; transgenic models; evolution of developmental mechanisms; zebrafish models of disease including Parkinson's disease
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Special Issue Information

Dear Colleagues,

The neurotransmitter dopamine plays crucial roles within the central nervous system, influencing multiple neural pathways and associated behaviors such as locomotion, reward mechanisms, neuroendocrine control, and emotion, to name but a few. Dysfunction of dopamine systems, including degeneration of dopamine neurons, is associated with numerous diseases. Some of the medications used to treat these diseases act by altering the effects of dopamine. This Special Issue on “Dopamine in Health and Disease 2.0” will present a selection of original research papers or reviews that address such topics as cellular mechanisms of disease affecting dopaminergic systems, genetic influences on dopamine neuron health and function, animal models of dopamine neuron loss and regeneration, and novel therapeutics for pathologies that involve dopamine neurons.

Prof. Dr. Marc Ekker
Guest Editor

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Keywords

  • dopamine
  • disease models
  • mitochondria
  • Parkinson’s disease
  • schizophrenia

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Related Special Issue

Published Papers (4 papers)

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Research

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19 pages, 3138 KiB  
Article
Social Interactions of Dat-Het Epi-Genotypes Differing for Maternal Origins: The Development of a New Preclinical Model of Socio-Sexual Apathy
by Anna Brancato, Sara L. M. Lo Russo, Anna Sara Liberati, Cristiana Carbone, Silvia Zelli, Giovanni Laviola, Carla Cannizzaro and Walter Adriani
Biomedicines 2021, 9(7), 778; https://doi.org/10.3390/biomedicines9070778 - 5 Jul 2021
Cited by 5 | Viewed by 2355
Abstract
Social interaction is essential for life but is impaired in many psychiatric disorders. We presently focus on rats with a truncated allele for dopamine transporter (DAT). Since heterozygous individuals possess only one non-mutant allele, epigenetic interactions may unmask latent genetic predispositions. Homogeneous “maternal” [...] Read more.
Social interaction is essential for life but is impaired in many psychiatric disorders. We presently focus on rats with a truncated allele for dopamine transporter (DAT). Since heterozygous individuals possess only one non-mutant allele, epigenetic interactions may unmask latent genetic predispositions. Homogeneous “maternal” heterozygous offspring (termed MAT-HET) were born from dopamine-transporter knocked-out (DAT-KO) male rats and wild-type (WT) mothers; “mixed” heterozygous offspring (termed MIX-HET) were born from both DAT-heterozygous parents. Their social behavior was assessed by: partner-preference (PPT), social-preference (SPT) and elicited-preference (EPT) tests. During the PPT, focal MIX-HET and MAT-HET males had a choice between two WT females, one in estrous and the other not. In the SPT, they met as stimulus either a MIX-HET or a WT male. In the EPT, the preference of focal male WT rats towards either a MIX- or a MAT-HET stimulus was tested. MIX-HET focal males showed an abnormal behavior, seeming not interested in socializing either with a female in estrous or with another male if MIX-HET. Focal MAT-HET males, instead, were very attracted by the female in estrous, but totally ignored the MIX-HET male. We assessed the expression of noradrenaline transporter (NET) in prefrontal cortex, hippocampus and hypothalamus, finding differences between the two offspring. MIX-HETs’ hypothalamus and hippocampus showed less NET than MAT-HETs, while the latter, in turn, showed higher NET than WTs. These behavioral differences between heterozygous groups may be attributed to different maternal cares received. Results allow preclinical understanding of epigenetic factors involved in social-behavior abnormalities, typical of many psychiatric disorders. Full article
(This article belongs to the Special Issue Dopamine in Health and Disease 2.0)
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Review

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24 pages, 1677 KiB  
Review
Role of Microbiota-Gut-Brain Axis in Regulating Dopaminergic Signaling
by Sevag Hamamah, Armin Aghazarian, Anthony Nazaryan, Andras Hajnal and Mihai Covasa
Biomedicines 2022, 10(2), 436; https://doi.org/10.3390/biomedicines10020436 - 13 Feb 2022
Cited by 98 | Viewed by 18275
Abstract
Dopamine is a neurotransmitter that plays a critical role both peripherally and centrally in vital functions such as cognition, reward, satiety, voluntary motor movements, pleasure, and motivation. Optimal dopamine bioavailability is essential for normal brain functioning and protection against the development of neurological [...] Read more.
Dopamine is a neurotransmitter that plays a critical role both peripherally and centrally in vital functions such as cognition, reward, satiety, voluntary motor movements, pleasure, and motivation. Optimal dopamine bioavailability is essential for normal brain functioning and protection against the development of neurological diseases. Emerging evidence shows that gut microbiota have significant roles in maintaining adequate concentrations of dopamine via intricate, bidirectional communication known as the microbiota-gut-brain axis. The vagus nerve, immune system, hypothalamus–pituitary–adrenal axis, and microbial metabolites serve as important mediators of the reciprocal microbiota-gut-brain signaling. Furthermore, gut microbiota contain intrinsic enzymatic activity that is highly involved in dopamine metabolism, facilitating dopamine synthesis as well as its metabolite breakdown. This review examines the relationship between key genera of gut microbiota such as Prevotella, Bacteroides, Lactobacillus, Bifidobacterium, Clostridium,Enterococcus, and Ruminococcus and their effects on dopamine. The effects of gut dysbiosis on dopamine bioavailability and the subsequent impact on dopamine-related pathological conditions such as Parkinson’s disease are also discussed. Understanding the role of gut microbiota in modulating dopamine activity and bioavailability both in the periphery and in the central nervous system can help identify new therapeutic targets as well as optimize available methods to prevent, delay, or restore dopaminergic deficits in neurologic and metabolic disorders. Full article
(This article belongs to the Special Issue Dopamine in Health and Disease 2.0)
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22 pages, 1300 KiB  
Review
Chemical and Biological Molecules Involved in Differentiation, Maturation, and Survival of Dopaminergic Neurons in Health and Parkinson’s Disease: Physiological Aspects and Clinical Implications
by Giulia Gaggi, Andrea Di Credico, Pascal Izzicupo, Giovanni Iannetti, Angela Di Baldassarre and Barbara Ghinassi
Biomedicines 2021, 9(7), 754; https://doi.org/10.3390/biomedicines9070754 - 29 Jun 2021
Cited by 14 | Viewed by 3650
Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative disease characterized by a specific and progressive loss of dopaminergic (DA) neurons and dopamine, causing motor dysfunctions and impaired movements. Unfortunately, available therapies can partially treat the motor symptoms, but they have no [...] Read more.
Parkinson’s disease (PD) is one of the most common neurodegenerative disease characterized by a specific and progressive loss of dopaminergic (DA) neurons and dopamine, causing motor dysfunctions and impaired movements. Unfortunately, available therapies can partially treat the motor symptoms, but they have no effect on non-motor features. In addition, the therapeutic effect reduces gradually, and the prolonged use of drugs leads to a significative increase in the number of adverse events. For these reasons, an alternative approach that allows the replacement or the improved survival of DA neurons is very appealing for the treatment of PD patients and recently the first human clinical trials for DA neurons replacement have been set up. Here, we review the role of chemical and biological molecules that are involved in the development, survival and differentiation of DA neurons. In particular, we review the chemical small molecules used to differentiate different type of stem cells into DA neurons with high efficiency; the role of microRNAs and long non-coding RNAs both in DA neurons development/survival as far as in the pathogenesis of PD; and, finally, we dissect the potential role of exosomes carrying biological molecules as treatment of PD. Full article
(This article belongs to the Special Issue Dopamine in Health and Disease 2.0)
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Other

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16 pages, 1072 KiB  
Perspective
Frequency of the Dopamine Receptor D3 (rs6280) vs. Opioid Receptor µ1 (rs1799971) Polymorphic Risk Alleles in Patients with Opioid Use Disorder: A Preponderance of Dopaminergic Mechanisms?
by Marjorie C. Gondré-Lewis, Igor Elman, Tanya Alim, Edwin Chapman, Beverlyn Settles-Reaves, Carine Galvao, Mark S. Gold, David Baron, Shan Kazmi, Eliot Gardner, Ashim Gupta, Catherine Dennen and Kenneth Blum
Biomedicines 2022, 10(4), 870; https://doi.org/10.3390/biomedicines10040870 - 7 Apr 2022
Cited by 8 | Viewed by 2748
Abstract
While opioids are a powerful class of drugs that inhibit transmission of pain signals, their use is tarnished by the current epidemic of opioid use disorder (OUD) and overdose deaths. Notwithstanding published reports, there remain gaps in our knowledge of opioid receptor mechanisms [...] Read more.
While opioids are a powerful class of drugs that inhibit transmission of pain signals, their use is tarnished by the current epidemic of opioid use disorder (OUD) and overdose deaths. Notwithstanding published reports, there remain gaps in our knowledge of opioid receptor mechanisms and their role in opioid seeking behavior. Thus, novel insights into molecular, neurogenetic and neuropharmacological bases of OUD are needed. We propose that an addictive endophenotype may not be entirely specific to the drug of choice but rather may be generalizable to altered brain reward circuits impacting net mesocorticolimbic dopamine release. We suggest that genetic or epigenetic alterations across dopaminergic reward systems lead to uncontrollable self-administration of opioids and other drugs. For instance, diminished availability via knockout of dopamine D3 receptor (DRD3) increases vulnerability to opioids. Building upon this concept via the use of a sophisticated polymorphic risk analysis in a human cohort of chronic opioid users, we found evidence for a higher frequency of polymorphic DRD3 risk allele (rs6280) than opioid receptor µ1 (rs1799971). In conclusion, while opioidergic mechanisms are involved in OUD, dopamine-related receptors may have primary influence on opioid-seeking behavior in African Americans. These findings suggest OUD-targeted novel and improved neuropharmacological therapies may require focus on DRD3-mediated regulation of dopaminergic homeostasis. Full article
(This article belongs to the Special Issue Dopamine in Health and Disease 2.0)
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