Encapsulation of monoamine neurotransmitters and trace amines by amphiphilic anionic calix[5]arene micelles

(1) Background: Monoamine neurotransmitters play essential roles in the normal functioning of our nervous system. However, the metabolism of monoamine neurotransmitters is accompanied by the production of neurotoxic metabolites, and inefficient removal of the metabolites has been suggested to cause neurodegeneration. (2) Methods: To examine the effect of reduced activity of catechol-O-methyltransferase (COMT) and aldehyde dehydrogenase 2 (ALDH2) conferred by single nucleotide polymorphisms COMT rs4680(A) and ALDH2 rs671(A) on the symptoms of patients with Parkinson’s disease (PD), a total of 114 PD patients were recruited cross-sectionally and received genotyping for rs4680 and rs671 along with MDS-UPDRS evaluation. (3) Results: We found that patients carrying rs4680(A) had more severe bradykinesia in the upper extremity and rest tremor. Besides, patients carrying rs671(A) had more difficulty maintaining personal hygiene, while patients with genotype rs671(GG) had higher scores in the item “depressed mood.” More importantly, we found the effect of rs4680 to be moderated by rs671 SNP for the symptom of “hand movements.” The detrimental impact of rs4680(A) is more pronounced in the presence of genotype rs671(GG). (4) Conclusions: This study facilitates a deeper understanding of the detrimental effect of reduced activity of COMT and ALDH2 conferred by genetic variation and provides novel insight into the interactions between enzymes metabolizing monoamine neurotransmitters in the pathogenesis of PD.

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Limbic Expression of mRNA Coding for Chemoreceptors in Human Brain—Lessons from Brain Atlases

International Journal of Molecular Sciences ◽

10.3390/ijms22136858 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6858

Author(s):

Fanny Gaudel ◽

Gaëlle Guiraudie-Capraz ◽

François Féron

Keyword(s):

G Proteins ◽

The Body ◽

Trace Amines ◽

Chemical Senses ◽

Brain Areas ◽

Genes Encoding ◽

The Central Nervous System ◽

Human Brains ◽

The Brain ◽

Brain Atlases

Animals strongly rely on chemical senses to uncover the outside world and adjust their behaviour. Chemical signals are perceived by facial sensitive chemosensors that can be clustered into three families, namely the gustatory (TASR), olfactory (OR, TAAR) and pheromonal (VNR, FPR) receptors. Over recent decades, chemoreceptors were identified in non-facial parts of the body, including the brain. In order to map chemoreceptors within the encephalon, we performed a study based on four brain atlases. The transcript expression of selected members of the three chemoreceptor families and their canonical partners was analysed in major areas of healthy and demented human brains. Genes encoding all studied chemoreceptors are transcribed in the central nervous system, particularly in the limbic system. RNA of their canonical transduction partners (G proteins, ion channels) are also observed in all studied brain areas, reinforcing the suggestion that cerebral chemoreceptors are functional. In addition, we noticed that: (i) bitterness-associated receptors display an enriched expression, (ii) the brain is equipped to sense trace amines and pheromonal cues and (iii) chemoreceptor RNA expression varies with age, but not dementia or brain trauma. Extensive studies are now required to further understand how the brain makes sense of endogenous chemicals.

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Nanosilver-embedded silicon nanowires as a SERS-active substrate for the ultrasensitive detection of monoamine neurotransmitters

Surfaces and Interfaces ◽

10.1016/j.surfin.2021.101181 ◽

2021 ◽

pp. 101181

Author(s):

Van-The Vo ◽

Viet-Duc Phung ◽

Sang-Wha Lee

Keyword(s):

Silicon Nanowires ◽

Ultrasensitive Detection ◽

Monoamine Neurotransmitters ◽

Active Substrate ◽

Sers Active Substrate

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Cerebrospinal fluid monoamine levels in central hypersomnolence disorders

SLEEP ◽

10.1093/sleep/zsab012 ◽

2021 ◽

Author(s):

Lucie Barateau ◽

Isabelle Jaussent ◽

Julien Roeser ◽

Claudio Ciardiello ◽

Thomas S Kilduff ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Daytime Sleepiness ◽

Direct Consequence ◽

Trace Amines ◽

Idiopathic Hypersomnia ◽

National Reference Center ◽

Drug Free ◽

Sleep Propensity

Abstract Study objectives Whether the cause of daytime sleepiness in narcolepsy type 1 (NT1) is a direct consequence of the loss of orexin neurons or whether low orexin reduces the efficacy of the monoaminergic systems to promote wakefulness is unclear. The neurobiology underlying sleepiness in other central hypersomnolence disorders, narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH), is currently unknown. Methods Eleven biogenic amines including the monoaminergic neurotransmitters and their metabolites and five trace amines were measured in the cerebrospinal fluid (CSF) of 94 drug-free subjects evaluated at the French National Reference Center for Narcolepsy: 39 NT1(orexin-deficient) patients, 31 patients with objective sleepiness non-orexin deficient (NT2 and IH), and 24 patients without objective sleepiness. Results Three trace amines were undetectable in the sample: Tryptamine, Octopamine, and 3-iodothyronamine. No significant differences were found among the three groups for quantified monoamines and their metabolites in crude and adjusted models; however, CSF 5-HIAA levels tended to increase in NT1 compared to other patients after adjustment. Most of biomarkers were not associated with ORX-A levels, clinical or neurophysiological parameters, but a few biomarkers (e.g., MHPG and norepinephrine) correlated with daytime sleepiness and high REM sleep propensity. Conclusion We found no striking differences among CSF monoamines, their metabolites and trace amine levels, and few associations between them and key clinical or neurophysiological parameters in NT1,NT2/IH and patients without objective sleepiness. Although mostly negative, these findings are a significant contribution to our understanding of the neurobiology of hypersomnolence in these disorders that remain mysterious and deserve further exploration.

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Synergistic Effect of Several Neurotransmitters in PFC-NAc-VTA Neural Circuit for the Anti-Depression Effect of Shuganheweitang in a Chronic Unpredictable Mild Stress Model

Natural Product Communications ◽

10.1177/1934578x211002415 ◽

2021 ◽

Vol 16 (3) ◽

pp. 1934578X2110024

Author(s):

Xin Chen ◽

Yuanchun Ma ◽

Xiongjun Mou ◽

Hao Liu ◽

Hao Ming ◽

...

Keyword(s):

Animal Behavior ◽

Neural Circuit ◽

Concentration Level ◽

Brain Regions ◽

Mild Stress ◽

Depression Effect ◽

Monoamine Neurotransmitters ◽

Reward Circuitry ◽

High Doses ◽

The Brain

Depression, a major worldwide mental disorder, leads to massive disability and can result in death. The PFC-NAc-VTA neuro circuit is related to emotional, neurovegetative, and cognitive functions, which emerge as a circuit-level framework for understanding reward deficits in depression. Neurotransmitters, which are widely distributed in different brain regions, are important detected targets for the evaluation of depression. Shuganheweitang (SGHWT) is a popular prescription in clinical therapy for depression. In order to investigate its possible pharmacodynamics and anti-depressive mechanism, the complex plant material was separated into different fractions. These in low and high doses, along with low and high doses of SGHWT were tested in animal behavior tests. The low and high doses of SGHWT were more effective than the various fractions, which indicate the importance of synergistic function in traditional Chinese medicine. Furthermore, amino acid (GABA, Glu) and monoamine neurotransmitters (DA, 5-HT, NA, 5-HIAA) in the PFC-NAc-VTA neuro circuit were investigated by UPLC-MS/MS. The level trend of DA and 5-HT were consistent in the PFC-NAc-VTA neuro circuit, whereas 5-HIAA was decreased in the PFC, Glu was decreased in the PFC and VTA, and NA and GABA were decreased in the NAc. The results indicate that the pathogenesis of depression is associated with dysfunction of the PFC-NAc-VTA neural circuit, mainly through the neural projection effects of neurotransmitters associated with various brain regions in the neural circuit. PCA and OPLS-DA score plots demonstrated the similarities of individuals within each group and the differences among the groups. In this study, SGHWT could regulate the concentration level of different neurotransmitters in the PFC-NAc-VTA neuro circuit to improve the depression, which benefitted from the recognition of the brain reward circuitry in mood disorders.

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