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14 pages, 934 KiB

Open AccessArticle

Evaluation of Peripheral Blood Concentrations of Phoenixin, Spexin, Nesfatin-1 and Kisspeptin as Potential Biomarkers of Bipolar Disorder in the Pediatric Population

by Lena Cichoń, Artur Pałasz, Krzysztof M. Wilczyński, Aleksandra Suszka-Świtek, Anna Żmijowska, Ireneusz Jelonek and Małgorzata Janas-Kozik

Biomedicines 2024, 12(1), 84; https://doi.org/10.3390/biomedicines12010084 - 29 Dec 2023

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Abstract

There are some initial suggestions in the literature that phoenixin, spexin, nesfatin-1 and kisspeptin may play a role in the pathogenesis of affective disorders. Therefore, they may also be cautiously considered as potential diagnostic or predictive biomarkers of BD. This study aimed to [...] Read more.

There are some initial suggestions in the literature that phoenixin, spexin, nesfatin-1 and kisspeptin may play a role in the pathogenesis of affective disorders. Therefore, they may also be cautiously considered as potential diagnostic or predictive biomarkers of BD. This study aimed to evaluate the levels of the aforementioned neuropeptides in the peripheral blood of children and adolescents with bipolar. This study included 122 individuals: 67 persons with diagnosed bipolar disorder types I and II constituted the study group, and 55 healthy persons were included in the control group. Statistically significant differences in the concentrations of neuropeptides between the control and study groups were noted in relation to nesfatin-1 and spexin (although spexin lost statistical significance after introducing the Bonferroni correction). In a logistic regression analysis, an increased risk of bipolar disorder was noted for a decrease in nesfatin-1 concentration. Lower levels of nesfatin-1 seemed to be a significant risk factor for the development of bipolar disorder types I and II. Furthermore, the occurrence of bipolar disorder was associated with significantly elevated levels of spexin. None of the analyzed neuropeptides was significantly correlated with the number of symptoms of bipolar disorder. Full article

(This article belongs to the Special Issue Neuropeptides, Dopamine and Their Interactions in Neuroscience)

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18 pages, 8531 KiB

Open AccessArticle

Exploring the Interaction of Indole-3-Acetonitrile with Neuroblastoma Cells: Understanding the Connection with the Serotonin and Dopamine Pathways

by Catarina Moura, Ana Salomé Correia and Nuno Vale

Biomedicines 2023, 11(12), 3325; https://doi.org/10.3390/biomedicines11123325 - 16 Dec 2023

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Abstract

Indole-3-acetonitrile, a compound produced by bacteria and plants as a defense and survival signal in response to attacks, has been recently discovered as a metabolite produced by human cancer cells. This discovery suggests a potential association between IAN and cancer progression in patients. [...] Read more.

Indole-3-acetonitrile, a compound produced by bacteria and plants as a defense and survival signal in response to attacks, has been recently discovered as a metabolite produced by human cancer cells. This discovery suggests a potential association between IAN and cancer progression in patients. Consequently, the aim of this work was to study the effects of IAN on a specific cancer cell line, SH-SY5Y, and elucidate its connection to the serotonin and dopamine pathways by examining the precursors of these neurotransmitters. To achieve this, a cellular viability assay was conducted, along with a morphological evaluation of the cells under both normal and stress conditions. Our results demonstrated that for the highest concentrations in our study, IAN was able to reduce the cellular viability of the cells. Furthermore, when IAN was combined with the amino acids that originate the neurotransmitters, it was possible to observe that in both combinations there was a decrease in the viability of the cells. Thus, IAN may in fact have some influence on both the serotonin and dopamine pathways since changes in cell viability were observed when it was added together with the amino acids. This preliminary study indicates the presence of an interaction between IAN and neuroblastoma cells that justifies further exploration and study. Full article

(This article belongs to the Special Issue Neuropeptides, Dopamine and Their Interactions in Neuroscience)

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15 pages, 6451 KiB

Open AccessArticle

AgRP Neuron-Specific Ablation Represses Appetite, Energy Intake, and Somatic Growth in Larval Zebrafish

by Chiu-Ya Lin, Kun-Yun Yeh, Hsin-Hung Lai and Guor Mour Her

Biomedicines 2023, 11(2), 499; https://doi.org/10.3390/biomedicines11020499 - 9 Feb 2023

Cited by 1 | Viewed by 1861

Abstract

Neuronal circuits regulating appetite are dominated by arcuate nucleus neurons, which include appetite-promoting and -suppressing neurons that release the orexigenic neuropeptide agouti-related protein (AgRP) and anorexigenic neuropeptide pro-opiomelanocortin, respectively, to compete for melanocortin receptors to modulate feeding behavior. In this study, we expressed [...] Read more.

Neuronal circuits regulating appetite are dominated by arcuate nucleus neurons, which include appetite-promoting and -suppressing neurons that release the orexigenic neuropeptide agouti-related protein (AgRP) and anorexigenic neuropeptide pro-opiomelanocortin, respectively, to compete for melanocortin receptors to modulate feeding behavior. In this study, we expressed novel agrp promoters, including different lengths of the 5’ flanking regions of the agrp gene (4749 bp) in the zebrafish genome. We used the agrp promoter to derive the enhanced green fluorescent protein (EGFP)-nitroreductase (NTR) fusion protein, allowing expression of the green fluorescence signal in the AgRP neurons. Then, we treated the transgenic zebrafish AgRP4.7^NTR (Tg [agrp-EGFP-NTR]) with metronidazole to ablate the AgRP neurons in the larvae stage and observed a decline in their appetite and growth. The expression of most orexigenic and growth hormone/insulin-like growth factor axis genes decreased, whereas that of several anorexigenic genes increased. Our findings demonstrate that AgRP is a critical regulator of neuronal signaling for zebrafish appetite and energy intake control. Thus, AgRP4.7^NTR can be used as a drug-screening platform for therapeutic targets to treat human appetite disorders, including obesity. Furthermore, the unique agrp promoter we identified can be a powerful tool for research on AgRP neurons, especially AgRP neuron-mediated pathways in the hypothalamus, and appetite. Full article

(This article belongs to the Special Issue Neuropeptides, Dopamine and Their Interactions in Neuroscience)

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17 pages, 1413 KiB

Open AccessArticle

Distinctive Neuroanatomic Regions Involved in Cocaine-Induced Behavioral Sensitization in Mice

by Renan dos Santos-Baldaia, Raphael Wuo-Silva, Viviam Sanabria, Marilia A. Baldaia, Thais S. Yokoyama, Antonio Augusto Coppi, André W. Hollais, Eduardo A. V. Marinho, Alexandre J. Oliveira-Lima and Beatriz M. Longo

Biomedicines 2023, 11(2), 383; https://doi.org/10.3390/biomedicines11020383 - 27 Jan 2023

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Abstract

The present study aimed to characterize the phenomenon of behavioral sensitization to cocaine and to identify neuroanatomical structures involved in the induction and expression phases of this phenomenon. For this, in experiment 1 (induction phase), mice were treated with saline or cocaine every [...] Read more.

The present study aimed to characterize the phenomenon of behavioral sensitization to cocaine and to identify neuroanatomical structures involved in the induction and expression phases of this phenomenon. For this, in experiment 1 (induction phase), mice were treated with saline or cocaine every second day for 15 days (conditioning period), in the open-field or in their home-cages. In experiment 2 (expression phase), the same protocol was followed, except that after the conditioning period the animals were not manipulated for 10 days, and after this interval, animals were challenged with cocaine. Neuroanatomical structures involved in the induction and expression phases were identified by stereological quantification of c-Fos staining in the dorsomedial prefrontal cortex (dmPFC), nucleus accumbens core (NAc core and shell (NAc shell), basolateral amygdala (BLA), and ventral tegmental area (VTA). Neuroanatomical analysis indicated that in the induction phase, cocaine-conditioned animals had higher expression of c-Fos in the dmPFC, NAc core, BLA, and VTA, whereas in the expression phase, almost all areas had higher expression except for the VTA. Therefore, environmental context plays a major role in the induction and expression of behavioral sensitization, although not all structures that compose the mesolimbic system contribute to this phenomenon. Full article

(This article belongs to the Special Issue Neuropeptides, Dopamine and Their Interactions in Neuroscience)

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7 pages, 1184 KiB

Open AccessCommunication

Does TRODAT-1 SPECT Uptake Correlate with Cerebrospinal Fluid α-Synuclein Levels in Mid-Stage Parkinson’s Disease?

by Artur M. Coutinho, Maria Gabriela Ghilardi, Ana Carolina P. Campos, Elba Etchebehere, Fernanda C. Fonoff, Rubens G. Cury, Rosana L. Pagano, Raquel C. R. Martinez and Erich T. Fonoff

Biomedicines 2023, 11(2), 296; https://doi.org/10.3390/biomedicines11020296 - 20 Jan 2023

Cited by 1 | Viewed by 1319

Abstract

Background: Parkinson’s disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons with impaired motor and non-motor symptoms. It has been suggested that motor asymmetry could be caused due to an imbalance in dopamine levels, as visualized by dopamine transporter single [...] Read more.

Background: Parkinson’s disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons with impaired motor and non-motor symptoms. It has been suggested that motor asymmetry could be caused due to an imbalance in dopamine levels, as visualized by dopamine transporter single emission computed tomography test (DAT-SPECT), which might be related to indirect measures of neurodegeneration, evaluated by the Montreal Cognitive Assessment (MOCA) and α-synuclein levels in the cerebrospinal fluid (CSF). Therefore, this study aimed to understand the correlation between disease laterality, DAT-SPECT, cognition, and α-synuclein levels in PD. Methods: A total of 28 patients in the moderate-advanced stage of PD were subjected to neurological evaluation, TRODAT-1-SPECT/CT imaging, MOCA, and quantification of the levels of α-synuclein. Results: We found that α-synuclein in the CSF was correlated with global cognition (positive correlation, r² = 0.3, p = 0.05) and DAT-SPECT concentration in the putamen (positive correlation, r² = 0.4, p = 0.005), and striatum (positive correlation, r² = 0.2, p = 0.03), thus working as a neurodegenerative biomarker. No other correlations were found between DAT-SPECT, CSF α-synuclein, and cognition, thus suggesting that they may be lost with disease progression. Conclusions: Our data highlight the importance of understanding the dysfunction of the dopaminergic system in the basal ganglia and its complex interactions in modulating cognition. Full article

(This article belongs to the Special Issue Neuropeptides, Dopamine and Their Interactions in Neuroscience)

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12 pages, 564 KiB

Open AccessArticle

Intranasal Oxytocin Modulates Decision-Making Depending on Outcome Predictability—A Randomized Within-Subject Controlled Trial in Healthy Males

by Paul Theo Zebhauser, Ana Macchia, Edward Gold, Stephanie Salcedo, Bethany Burum, Miguel Alonso-Alonso, Daniel T. Gilbert, Alvaro Pascual-Leone and Anna-Katharine Brem

Biomedicines 2022, 10(12), 3230; https://doi.org/10.3390/biomedicines10123230 - 12 Dec 2022

Cited by 1 | Viewed by 1394

Abstract

Oxytocin (OT) has been extensively studied with regard to its socio-cognitive and -behavioral effects. Its potential as a therapeutic agent is being discussed for a range of neuropsychiatric conditions. However, there is limited evidence of its effects on non-social cognition in general and [...] Read more.

Oxytocin (OT) has been extensively studied with regard to its socio-cognitive and -behavioral effects. Its potential as a therapeutic agent is being discussed for a range of neuropsychiatric conditions. However, there is limited evidence of its effects on non-social cognition in general and decision-making in particular, despite the importance of these functions in neuropsychiatry. Using a crossover/within-subject, blinded, randomized design, we investigated for the first time if intranasal OT (24 IU) affects decision-making differently depending on outcome predictability/ambiguity in healthy males. The Iowa Gambling Task (IGT) and the Cambridge Risk Task (CRT) were used to assess decision-making under low outcome predictability/high ambiguity and under high outcome probability/low ambiguity, respectively. After administration of OT, subjects performed worse and exhibited riskier performance in the IGT (low outcome predictability/high ambiguity), whereas they made borderline-significant less risky decisions in the CRT (high outcome probability/low ambiguity) as compared to the control condition. Decision-making in healthy males may therefore be influenced by OT and adjusted as a function of contextual information, with implications for clinical trials investigating OT in neuropsychiatric conditions. Full article

(This article belongs to the Special Issue Neuropeptides, Dopamine and Their Interactions in Neuroscience)

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13 pages, 907 KiB

Open AccessArticle

The Role of Intraamygdaloid Oxytocin and D2 Dopamine Receptors in Reinforcement in the Valproate-Induced Autism Rat Model

by Kristóf László, Dávid Vörös, Orsolya Kiss, Bettina Réka László, Tamás Ollmann, László Péczely, Kitti Mintál, Attila Tóth, Anita Kovács, Olga Zagoracz, Erika Kertes, Veronika Kállai, Beáta Berta, Zoltán Karádi and László Lénárd

Biomedicines 2022, 10(9), 2309; https://doi.org/10.3390/biomedicines10092309 - 16 Sep 2022

Cited by 1 | Viewed by 1848

Abstract

Background: autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting around 1 out of 68 children and its incidence shows an increasing tendency. There is currently no effective treatment for ASD. In autism research, the valproate (VPA)-induced autism rodent model is widely accepted. [...] Read more.

Background: autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting around 1 out of 68 children and its incidence shows an increasing tendency. There is currently no effective treatment for ASD. In autism research, the valproate (VPA)-induced autism rodent model is widely accepted. Our previous results showed that intraamygdaloid oxytocin (OT) has anxiolytic effects on rats showing autistic signs under the VPA-induced autism model. Methods: rats were stereotaxically implanted with guide cannulae bilaterally and received intraamygdaloid microinjections. In the present study, we investigated the possible role of intraamygdaloid OT and D2 dopamine (DA) receptors on reinforcement using VPA-treated rats in a conditioned place preference test. OT and/or an OT receptor antagonist or a D2 DA antagonist were microinjected into the central nucleus of the amygdala (CeA). Results: valproate-treated rats receiving 10 ng OT spent significantly longer time in the treatment quadrant during the test session of the conditioned place preference test. Prior treatment with an OT receptor antagonist or with a D2 DA receptor antagonist blocked the positive reinforcing effects of OT. The OT receptor antagonist or D2 DA antagonist in themselves did not influence the time rats spent in the treatment quadrant. Conclusions: Our results show that OT has positive reinforcing effects under the VPA-induced autism rodent model and these effects are OT receptor-specific. Our data also suggest that the DAergic system plays a role in the positive reinforcing effects of OT because the D2 DA receptor antagonist can block these actions. Full article

(This article belongs to the Special Issue Neuropeptides, Dopamine and Their Interactions in Neuroscience)

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14 pages, 1322 KiB

Open AccessArticle

Effect of D1- and D2-like Dopamine Receptor Antagonists on the Rewarding and Anxiolytic Effects of Neurotensin in the Ventral Pallidum

by Tamás Ollmann, László Lénárd, László Péczely, Beáta Berta, Erika Kertes, Olga Zagorácz, Edina Hormay, Kristóf László, Ádám Szabó, Rita Gálosi, Zoltán Karádi and Veronika Kállai

Biomedicines 2022, 10(9), 2104; https://doi.org/10.3390/biomedicines10092104 - 28 Aug 2022

Cited by 1 | Viewed by 1666

Abstract

Background: Neurotensin (NT) acts as a neurotransmitter and neuromodulator in the central nervous system. It was shown previously that NT in the ventral pallidum (VP) has rewarding and anxiolytic effects. NT exerts its effect in interaction with dopamine (DA) receptors in numerous brain [...] Read more.

Background: Neurotensin (NT) acts as a neurotransmitter and neuromodulator in the central nervous system. It was shown previously that NT in the ventral pallidum (VP) has rewarding and anxiolytic effects. NT exerts its effect in interaction with dopamine (DA) receptors in numerous brain areas; however, this has not yet been investigated in the VP. The aim of this study was to examine whether the inhibition of D1-like and D2-like DA receptors of the VP can modify the above mentioned effects of NT. Methods: Microinjection cannulas were implanted by means of stereotaxic operations into the VP of male Wistar rats. The rewarding effect of NT was examined by means of a conditioned place preference test. Anxiety was investigated with an elevated plus maze test. To investigate the possible interaction, D1-like DA receptor antagonist SCH23390 or D2-like DA receptor antagonist sulpiride were microinjected prior to NT. All of the drugs were also injected independently to analyze their effects alone. Results: In the present experiments, both the rewarding and anxiolytic effects of NT in the VP were prevented by both D1-like and D2-like DA receptor antagonists. Administered on their own, the antagonists did not influence reward and anxiety. Conclusion: Our present results show that the activity of the D1-like and D2-like DA receptors of the VP is a necessary requirement for both the rewarding and anxiolytic effects of NT. Full article

(This article belongs to the Special Issue Neuropeptides, Dopamine and Their Interactions in Neuroscience)

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19 pages, 1369 KiB

Open AccessReview

Insights into Calpain Activation and Rho-ROCK Signaling in Parkinson’s Disease and Aging

by Amy Gathings, Vandana Zaman, Narendra L. Banik and Azizul Haque

Biomedicines 2024, 12(5), 1074; https://doi.org/10.3390/biomedicines12051074 - 13 May 2024

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Abstract

Parkinson’s disease (PD), a progressive neurodegenerative disease, has no cure, and current therapies are not effective at halting disease progression. The disease affects mid-brain dopaminergic neurons and, subsequently, the spinal cord, contributing to many debilitating symptoms associated with PD. The GTP-binding protein, Rho, [...] Read more.

Parkinson’s disease (PD), a progressive neurodegenerative disease, has no cure, and current therapies are not effective at halting disease progression. The disease affects mid-brain dopaminergic neurons and, subsequently, the spinal cord, contributing to many debilitating symptoms associated with PD. The GTP-binding protein, Rho, plays a significant role in the cellular pathology of PD. The downstream effector of Rho, Rho-associated kinase (ROCK), plays multiple functions, including microglial activation and induction of inflammatory responses. Activated microglia have been implicated in the pathology of many neurodegenerative diseases, including PD, that initiate inflammatory responses, leading to neuron death. Calpain expression and activity is increased following glial activation, which triggers the Rho-ROCK pathway and induces inflammatory T cell activation and migration as well as mediates toxic α-synuclein (α-syn) aggregation and neuron death, indicating a pivotal role for calpain in the inflammatory and degenerative processes in PD. Increased calpain activity and Rho-ROCK activation may represent a new mechanism for increased oxidative damage in aging. This review will summarize calpain activation and the role of the Rho-ROCK pathway in oxidative stress and α-syn aggregation, their influence on the neurodegenerative process in PD and aging, and possible strategies and research directions for therapeutic intervention. Full article

(This article belongs to the Special Issue Neuropeptides, Dopamine and Their Interactions in Neuroscience)

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