Emotional vocalizations alter behaviors and neurochemical release into the amygdala.

The basolateral amygdala (BLA), a brain center of emotional expression, contributes to acoustic communication by first interpreting the meaning of social sounds in the context of the listener's internal state, then organizing the appropriate behavioral responses. We propose that modulatory neurochemicals such as acetylcholine (ACh) and dopamine (DA) provide internal-state signals to the BLA while an animal listens to social vocalizations. We tested this in a vocal playback experiment utilizing highly affective vocal sequences associated with either mating or restraint, then sampled and analyzed fluids within the BLA for a broad range of neurochemicals and observed behavioral responses of adult male and female mice. In male mice, playback of restraint vocalizations increased ACh release and usually decreased DA release, while playback of mating sequences evoked the opposite neurochemical release patterns. In non-estrus female mice, patterns of ACh and DA release with mating playback were similar to males. Estrus females, however, showed increased ACh, associated with vigilance, as well as increased DA, associated with reward-seeking. Experimental groups that showed increased ACh release also showed the largest increases in an aversive behavior. These neurochemical release patterns and several behavioral responses depended on a single prior experience with the mating and restraint behaviors. Our results support a model in which ACh and DA provide contextual information to sound analyzing BLA neurons that modulate their output to downstream brain regions controlling behavioral responses to social vocalizations.

Amphetamine exposure during embryogenesis changes expression and function of the dopamine transporter in Caenorhabditis elegans offspring.

The dopamine transporter (DAT) is a transmembrane protein that regulates dopamine (DA) neurotransmission by binding to and moving DA from the synaptic cleft back into the neurons. Besides moving DA and other endogenous monoamines, DAT is also a neuronal carrier for exogenous compounds such as the psychostimulant amphetamine (Amph), and several studies have shown that Amph-induced behaviors require a functional DAT. Here, we demonstrate that exposure to Amph during early development causes behavioral, functional, and epigenetic modifications at the Caenorhabditis elegans DAT gene homolog, dat-1, in C. elegans offspring. Specifically, we show that, while embryos exposed to Amph generate adults that produce offspring with no obvious behavioral alterations, both adults and offspring exhibit an increased behavioral response when challenged with Amph. Our functional studies suggest that a decrease in DAT-1 expression underlies the increased behavioral response to Amph seen in offspring. Moreover, our epigenetic data suggest that histone methylation is a mechanism utilized by Amph to maintain changes in DAT-1 expression in offspring. Taken together, our data reveal that Amph, by altering the epigenetic landscape of DAT, propagates long-lasting functional and behavioral changes in offspring.

Crosstalk between gut-brain axis: unveiling the mysteries of gut ROS in progression of Parkinson's disease.

"Path to a good mood lies through the gut." This statement seems to imply that it has long been believed that the gut is connected with the brain. Research has shown that eating food activates the reward system and releases dopamine (DA), establishing a link between the peripheral and central nervous system. At the same time, researchers also trust that the gut is involved in the onset of many diseases, including Parkinson's disease (PD), in which gastrointestinal dysfunction is considered a prevalent symptom. Reports suggest that PD starts from the gut and reaches the brain via the vagus nerve. Recent studies have revealed an intriguing interaction between the gut and brain, which links gut dysbiosis to the etiology of PD. This review aims to explore the mechanistic pathway how reactive oxygen species (ROS) generation in the gut affects the makeup and operation of the dopamine circuitry in the brain. Our primary concern is ROS generation in the gut, which disrupts the gut microbiome (GM), causing α-synuclein accumulation and inflammation. This trio contributes to the loss of DA neurons in the brain, resulting in PD development. This review also compiles pre-clinical and clinical studies on antioxidants, demonstrating that antioxidants reduce ROS and increase DA levels. Collectively, the study highlights the necessity of comprehending the gut-brain axis for unraveling the riddles of PD pathogenesis and considering new therapeutic approaches.

Roadmap for maternal behavior research in domestic dogs: lessons from decades of laboratory rodent work.

Maternal behavior research in laboratory rats has revealed important behavioral and neurobiological mechanisms governing the onset, maintenance and decline of maternal behavior. However, the extent to which these mechanisms are evolutionarily conserved across species is less clear. This manuscript proposes that examining these mechanisms in dogs may be a viable approach to test their generality and help bridge the gap between rodent and human research, as domestic dogs show greater individual differences and exhibit more human-like maternal characteristics than rodents. These aspects represent advantages over rodent models, which in turn allow systems biological approaches not available in rodents. Additionally, domestic dogs share similar social environments with humans, suffer from the same mental disorders as humans, and can be treated with the same medications. This paper begins with a summary of key findings and theoretical developments from decades of rat maternal behavior research, followed by a literature review of the extant maternal behavior research on dogs and related methodology, highlighting the unique behavioral characteristics of dog maternal behavior and similarities and differences from rat maternal behavior. Finally, several knowledge gaps in dog maternal behavior research, as well as the future research in this area is discussed. It concludes that research on dog maternal behavior will not only advance our understanding of the universality of the neurobiological and behavioral mechanisms in maternal behavior, but also improve our understanding of risk factors associated with postpartum mental disorders.

An Unexpected Phenomenon: A Case of Citalopram-Induced Dyskinesia.

Dyskinetic movements are characterized as hyperkinetic, repetitive movements of the extremities, facial, and oral musculature, most associated with prolonged dopamine D2 receptor blockade. In rare instances, dyskinetic movements can be brought on by selective serotonin reuptake inhibitor (SSRI) usage via an indirect D2 blockade mechanism, mimicking the D2 blockade observed with dopamine receptor blocking agents (DRBAs), such as in first-generation antipsychotics. This mimicked D2 blockade by SSRIs is said to be due to increased tonic inhibition by serotonin on dopaminergic neurons in the dopaminergic pathways of the brain, specifically the nigrostriatal pathway. In this case report, we look at a patient with a history of cerebral palsy who developed acute dyskinetic movements after short-term citalopram usage. The objective is to bring attention to the possible extrapyramidal side effects (EPS) of SSRI usage.

Revealing New Prospects: Antipsychotic Drugs Exert Anti-Tumor Effects against Gastric Cancer through Inducing Apoptosis.

BACKGROUND AND OBJECTIVE: Globally, Gastric Cancer (GC) ranks as the fifth leading cause of cancer-related deaths. GC is a multifaceted malignancy with diverse etiologies; however, understanding the shared molecular mechanisms can aid in discovering novel targeted therapies for GC. This study has employed a drug repositioning approach to explore new drug candidates for treating GC. METHODS: The human GC cell lines AGS, MKN-45, and KATO-III were treated with different concentrations of dopamine, cabergoline, thioridazine, and entacapone to determine effective doses and IC50 values. In vitro, cytotoxic activity on cancer cell lines was screened based on dose/time using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR) was used to measure the mRNA expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and Proliferating Cell Nuclear Antigen (PCNA) in each group. The percentage of apoptotic cells was evaluated using Annexin V/PI staining. RESULTS: Dopamine, cabergoline, thioridazine, and entacapone elicited cytotoxic effects on AGS and KATO-III cells in a dose-dependent manner and elevated the percentage of Annexin V-positive cells, suggesting the occurrence of apoptosis. The expression of Bcl-2 and PCNA was significantly decreased, whereas the expression of Bax was considerably increased in the AGS and KATO-III cells compared to that in the blank group (p < 0.05); however, no similar effect was observed in MKN-45 cells. CONCLUSION: Through in vitro experiments, this study provides evidence that the antipsychotic drugs cabergoline, dopamine, thioridazine, and entacapone can inhibit gastric cancer growth in AGS and KATO-III cells. These findings suggest that these drugs could be repurposed as novel therapeutic agents for the treatment of gastric cancer.

Why Don't You Just Eat? Neuroscience and the Enigma of Eating Disorders.

Eating disorders are severe psychiatric illnesses that are associated with high mortality. Research has identified environmental, psychological, and biological risk factors that could contribute to the psychopathology of eating disorders. Nevertheless, the patterns of self-starvation, binge eating, and purging behaviors are difficult to reconcile with the typical mechanisms that regulate appetite, hunger, and satiety. Here, the authors present a neuroscience and human brain imaging-based model to help explain the detrimental and often persistent behavioral patterns seen in individuals with eating disorders and why it is so difficult to overcome them. This model incorporates individual motivations to change eating, fear conditioning, biological adaptations of the brain and body, and the development of a vicious cycle that drives the individual to perpetuate those behaviors. This knowledge helps to explain these illnesses to patients and their families, and to develop more effective treatments, including biological interventions.

Ultra-Sensitive Simultaneous Detection of Dopamine and Acetaminophen over Hollow Porous AuAg Alloy Nanospheres.

Hollow porous AuAg nanospheres (AuAg HPNSs) were obtained through a simple solvothermal synthesis, complemented by a dealloying strategy. The hollow interior, open pore voids, and integral interconnected skeleton shell in AuAg HPNSs are beneficial for providing sufficient electrolyte diffusion and contacts, abundant active sites, and efficient electron transport. This specific structure and the favorable alloy synergism contribute to the superior electrocatalytic activity toward dopamine (DA) and acetaminophen (AC). AuAg HPNSs show high sensitivity, good selectivity, excellent sensing durability, and outstanding repeatability for amperometric assays of AC and DA. In particular, the AuAg-based sensors achieve effective ultrasensitive simultaneous analyses of AC and DA, exhibiting the characteristics of the wide linear range and low detection limit. With their prominent electrocatalytic activity and simple preparation methods, AuAg HPNSs present broad application prospects for constructing a highly responsive electrochemical sensing system.

Effects of Chronic Exposure to Low Doses of Rotenone on Dopaminergic and Cholinergic Neurons in the CNS of Hemigrapsus sanguineus.

Rotenone, as a common pesticide and insecticide frequently found in environmental samples, may be present in aquatic habitats worldwide. Exposure to low concentrations of this compound may cause alterations in the nervous system, thus contributing to Parkinsonian motor symptoms in both vertebrates and invertebrates. However, the effects of chronic exposure to low doses of rotenone on the activity of neurotransmitters that govern motor functions and on the specific molecular mechanisms leading to movement morbidity remain largely unknown for many aquatic invertebrates. In this study, we analyzed the effects that rotenone poisoning exerts on the activity of dopamine (DA) and acetylcholine (ACh) synthesis enzymes in the central nervous system (CNS) of Asian shore crab, Hemigrapsus sanguineus (de Haan, 1835), and elucidated the association of its locomotor behavior with Parkinson's-like symptoms. An immunocytochemistry analysis showed a reduction in tyrosine hydroxylase (TH) in the median brain and the ventral nerve cord (VNC), which correlated with the subsequent decrease in the locomotor activity of shore crabs. We also observed a variation in cholinergic neurons' activity, mostly in the ventral regions of the VNC. Moreover, the rotenone-treated crabs showed signs of damage to ChAT-lir neurons in the VNC. These data suggest that chronic treatment with low doses of rotenone decreases the DA level in the VNC and the ACh level in the brain and leads to progressive and irreversible reductions in the crab's locomotor activity, life span, and changes in behavior.

An atlas of GPCRs in dopamine neurons: Identification of the free fatty acid receptor 4 as a regulator of food and water intake.

Midbrain dopaminergic neurons (DANs) are subject to extensive metabotropic regulation, but the repertoire of G protein-coupled receptors (GPCRs) present in these neurons has not been mapped. Here, we isolate DANs from Dat-eGFP mice to generate a GPCR atlas by unbiased qPCR array expression analysis of 377 GPCRs. Combined with data mining of scRNA-seq databases, we identify multiple receptors in DAN subpopulations with 38 of these receptors representing the majority of transcripts. We identify 41 receptors expressed in midbrain DANs but not in non-DAN midbrain cells, including the free fatty acid receptor 4 (FFAR4). Functional expression of FFAR4 is validated by ex vivo Ca2+ imaging, and in vivo experiments support that FFAR4 negatively regulates food and water intake and bodyweight. In addition to providing a critical framework for understanding metabotropic DAN regulation, our data suggest fatty acid sensing by FFAR4 as a mechanism linking high-energy intake to the dopamine-reward pathway.

Bipolar electrochemical sensor with perylene diimide-based cathodic luminophore for dopamine detection and imaging.

Bipolar electrochemical microscopy (BEM), which visualizes the concentration distribution of molecular species in biological systems by electrochemiluminescence (ECL), is expected to be applied to the high-spatiotemporal-resolution imaging of biomolecules, enabling the analysis of cellular functions. In the past, the molecular species that could be imaged by BEM were generally restricted to oxidized molecules due to the limitation derived from the ECL mechanism of the luminophore. Recently, the imaging of dopamine (DA), a reduced molecule, was achieved using Ru (bpy)32+/glutathione disulfide (GSSG) as a cathodic luminophore. However, a large driving voltage was required for ECL generation, resulting in a low S/N ratio. In this study, we employed N,N'-dimethyl-3,4,9,10-perylenetetracarboxylic diimide (PDI-CH3)/potassium peroxodisulfate (K2S2O8), which is a cathodic luminophore that can be reduced at a nobler potential to produce ECL than [Ru(bpy)3]2+/GSSG. First, the ECL mechanism of PDI-CH3/K2S2O8 was elucidated by using a PDI-CH3 drop-cast glassy carbon electrode (GCE) immersed in K2S2O8 solution as the working electrode in a 3-electrode system. The PDI-CH3 drop-casted GCE, a single closed bipolar electrode (c-BPE), was used as the cathode in the successful quantification of 50-500 µmol L-1 DA in a sample chamber in which a c-BPE anode was immersed, resulting in a high S/N. The selective detection of DA in the presence of ascorbic acid was achieved by modifying the anode with Nafion. Finally, DA imaging was demonstrated using a commercially available anisotropic conducting film with PDI-CH3 coating on the cathode surface as a c-BPE array. The change in the concentration distribution in the inflow of DA was successfully imaged based on the change in the ECL intensity at the c-BPE cathode. This BEM system is expected to be useful for DA imaging of the brain.

The distribution of neurotransmitters in the brain circuitry: mesolimbic pathway and addiction.

Understanding the central nervous system (CNS) circuitry and its different neurotransmitters that underlie reward is essential to improve treatment for many common health issues, such as addiction. Here, we concentrate on understanding how the mesolimbic circuitry and neurotransmitters are organized and function, and how drug exposure affects synaptic and structural changes in this circuitry. While the role of some reward circuits, like the cerebral dopamine (DA)/glutamate (Glu)/gamma aminobutyric acid (GABA)ergic pathways, in drug reward, is well known, new research using molecular-based methods has shown functional alterations throughout the reward circuitry that contribute to various aspects of addiction, including craving and relapse. A new understanding of the fundamental connections between brain regions as well as the molecular alterations within these particular microcircuits, such as neurotrophic factor and molecular signaling or distinct receptor function, that underlie synaptic and structural plasticity evoked by drugs of abuse has been made possible by the ability to observe and manipulate neuronal activity within specific cell types and circuits. It is exciting that these discoveries from preclinical animal research are now being applied in the clinic, where therapies for human drug dependence, such as deep brain stimulation and transcranial magnetic stimulation, are being tested. Therefore, this chapter seeks to summarize the current understanding of the important brain regions (especially, mesolimbic circuitry) and neurotransmitters implicated in drug-related behaviors and the molecular mechanisms that contribute to altered connectivity between these areas, with the postulation that increased knowledge of the plasticity within the drug reward circuit will lead to new and improved treatments for addiction.

Patch and matrix striatonigral neurons differentially regulate locomotion.

The striatonigral neurons are known to promote locomotion1,2. These neurons reside in both the patch (also known as striosome) and matrix compartments of the dorsal striatum3-5. However, the specific contribution of patch and matrix striatonigral neurons to locomotion remain largely unexplored. Using molecular identifier Kringle-Containing Protein Marking the Eye and the Nose (Kremen1) and Calbidin (Calb1)6, we showed in mouse models that patch and matrix striatonigral neurons exert opposite influence on locomotion. While a reduction in neuronal activity in matrix striatonigral neurons precedes the cessation of locomotion, fiber photometry recording during self-paced movement revealed an unexpected increase of patch striatonigral neuron activity, indicating an inhibitory function. Indeed, optogenetic activation of patch striatonigral neurons suppressed locomotion, contrasting with the locomotion-promoting effect of matrix striatonigral neurons. Consistently, patch striatonigral neuron activation markedly inhibited dopamine release, whereas matrix striatonigral neuron activation initially promoted dopamine release. Moreover, the genetic deletion of inhibitory GABA-B receptor Gabbr1 in Aldehyde dehydrogenase 1A1-positive (ALDH1A1+) nigrostriatal dopaminergic neurons (DANs) completely abolished the locomotion-suppressing effect caused by activating patch striatonigral neurons. Together, our findings unravel a compartment-specific mechanism governing locomotion in the dorsal striatum, where patch striatonigral neurons suppress locomotion by inhibiting the activity of ALDH1A1+ nigrostriatal DANs.

Development of a Nanomarker for In Vivo Monitoring of Dopamine in Plants.

Dopamine, alongside norepinephrine and epinephrine, belongs to the catecholamine group, widely distributed across both plant and animal kingdoms. In mammals, these compounds serve as neurotransmitters with roles in glycogen mobilization. In plants, their synthesis is modulated in response to stress conditions aiding plant survival by emitting these chemicals, especially dopamine that relieves their resilience against stress caused by both abiotic and biotic factors. In present studies, there is a lack of robust methods to monitor the operations of dopamine under stress conditions or any adverse situations across the plant's developmental stages from cell to cell. In our study, we have introduced a groundbreaking approach to track dopamine generation and activity in various metabolic pathways by using the simple nitrogen and sulfur co-doped carbon quantum dots (N, S-CQDs). These CQDs exhibit dominant biocompatibility, negligible toxicity, and environmentally friendly characteristics using a quenching process for fluorometric dopamine detection. This innovative nanomarker can detect even small amounts of dopamine within plant cells, providing insights into plant responses to strain and anxiety. Confocal microscopy has been used to corroborate this occurrence and to provide visual proof of the process of binding dopamine with these N, S-CQDs inside the cells.

Changes in dorsomedial striatum activity during expression of goal-directed vs. habit-like cue-induced cocaine seeking.

A preclinical model of cue exposure therapy, cue extinction, reduces cue-induced cocaine seeking that is goal-directed but not habit-like. Goal-directed and habitual behaviors differentially rely on the dorsomedial striatum (DMS) and dorsolateral striatum (DLS), but the effects of cue extinction on dorsal striatal responses to cue-induced drug seeking are unknown. We used fiber photometry in rats trained to self-administer cocaine paired with an audiovisual cue to examine how dorsal striatal intracellular calcium and extracellular dopamine activity differs between goal-directed and habit-like cue-induced cocaine seeking and how it is impacted by cue extinction. After minimal fixed-ratio training, rats showed enhanced DMS and DLS calcium responses to cue-reinforced compared to unreinforced lever presses. After rats were trained on goal-promoting fixed ratio schedules or habit-promoting second-order schedules of reinforcement, different patterns of dorsal striatal calcium and dopamine responses to cue-reinforced lever presses emerged. Rats trained on habit-promoting second-order schedules showed reduced DMS calcium responses and enhanced DLS dopamine responses to cue-reinforced lever presses. Cue extinction reduced calcium responses during subsequent drug seeking in the DMS, but not in the DLS. Therefore, cue extinction may reduce goal-directed behavior through its effects on the DMS, whereas habit-like behavior and the DLS are unaffected.

Dopamine enhances GABAA receptor-mediated current amplitude in a subset of intrinsically photosensitive retinal ganglion cells.

Neuromodulation in the retina is crucial for effective processing of retinal signal at different levels of illuminance. Intrinsically photosensitive retinal ganglion cells (ipRGCs), the neurons that drive non-image forming visual functions, express a variety of neuromodulatory receptors that tune intrinsic excitability as well as synaptic inputs. Past research has examined actions of neuromodulators on light responsiveness of ipRGCs, but less is known about how neuromodulation affects synaptic currents in ipRGCs. To better understand how neuromodulators affect synaptic processing in ipRGC, we examine actions of opioid and dopamine agonists have on inhibitory synaptic currents in ipRGCs. Although µ-opioid receptor (MOR) activation had no effect on γ-aminobutyric acid (GABA) currents, dopamine (via the D1R) amplified GABAergic currents in a subset of ipRGCs. Furthermore, this D1R-mediated facilitation of the GABA conductance in ipRGCs was mediated by a cAMP/PKA-dependent mechanism. Taken together, these findings reinforce the idea that dopamine's modulatory role in retinal adaptation affects both non-image forming as well as image forming visual functions.

The distribution and evolutionary dynamics of dopaminergic neurons in molluscs.

Dopamine is one of the most versatile neurotransmitters in invertebrates. It's distribution and plethora of functions is likely coupled to feeding ecology, especially in Euthyneura (the largest clade of molluscs), which presents the broadest spectrum of environmental adaptations. Still, the analyses of dopamine-mediated signaling were dominated by studies of grazers. Here, we characterize the distribution of dopaminergic neurons in representatives of two distinct ecological groups: the sea angel - obligate predatory pelagic mollusc Clione limacina (Pteropoda, Gymnosomata) and its prey - the sea devil Limacina helicina (Pteropoda, Thecosomata) as well as the plankton eater Melibe leonina (Nudipleura, Nudibranchia). By using tyrosine hydroxylase-immunoreactivity (TH-ir) as a reporter, we showed that the dopaminergic system is moderately conservative among euthyneurans. Across all studied species, small numbers of dopaminergic neurons in the central ganglia contrast to significant diversification of TH-ir neurons in the peripheral nervous system, primarily representing sensory-like cells, which predominantly concentrated in the chemotactic areas and projecting afferent axons to the central nervous system. Combined with α-tubulin immunoreactivity, this study illuminates the unprecedented complexity of peripheral neural systems in gastropod molluscs, with lineage-specific diversification of sensory and modulatory functions.

Measures of the coupling between fluctuating brain network organization and heartbeat dynamics.

In recent years, there has been an increasing interest in studying brain-heart interactions. Methodological advancements have been proposed to investigate how the brain and the heart communicate, leading to new insights into some neural functions. However, most frameworks look at the interaction of only one brain region with heartbeat dynamics, overlooking that the brain has functional networks that change dynamically in response to internal and external demands. We propose a new framework for assessing the functional interplay between cortical networks and cardiac dynamics from noninvasive electrophysiological recordings. We focused on fluctuating network metrics obtained from connectivity matrices of EEG data. Specifically, we quantified the coupling between cardiac sympathetic-vagal activity and brain network metrics of clustering, efficiency, assortativity, and modularity. We validate our proposal using open-source datasets: one that involves emotion elicitation in healthy individuals, and another with resting-state data from patients with Parkinson's disease. Our results suggest that the connection between cortical network segregation and cardiac dynamics may offer valuable insights into the affective state of healthy participants, and alterations in the network physiology of Parkinson's disease. By considering multiple network properties, this framework may offer a more comprehensive understanding of brain-heart interactions. Our findings hold promise in the development of biomarkers for diagnostic and cognitive/motor function evaluation.

Computer-aided design and implementation of efficient biosynthetic pathways to produce high added-value products derived from tyrosine in Escherichia coli.

Developing efficient bioprocesses requires selecting the best biosynthetic pathways, which can be challenging and time-consuming due to the vast amount of data available in databases and literature. The extension of the shikimate pathway for the biosynthesis of commercially attractive molecules often involves promiscuous enzymes or lacks well-established routes. To address these challenges, we developed a computational workflow integrating enumeration/retrosynthesis algorithms, a toolbox for pathway analysis, enzyme selection tools, and a gene discovery pipeline, supported by manual curation and literature review. Our focus has been on implementing biosynthetic pathways for tyrosine-derived compounds, specifically L-3,4-dihydroxyphenylalanine (L-DOPA) and dopamine, with significant applications in health and nutrition. We selected one pathway to produce L-DOPA and two different pathways for dopamine-one already described in the literature and a novel pathway. Our goal was either to identify the most suitable gene candidates for expression in Escherichia coli for the known pathways or to discover innovative pathways. Although not all implemented pathways resulted in the accumulation of target compounds, in our shake-flask experiments we achieved a maximum L-DOPA titer of 0.71 g/L and dopamine titers of 0.29 and 0.21 g/L for known and novel pathways, respectively. In the case of L-DOPA, we utilized, for the first time, a mutant version of tyrosinase from Ralstonia solanacearum. Production of dopamine via the known biosynthesis route was accomplished by coupling the L-DOPA pathway with the expression of DOPA decarboxylase from Pseudomonas putida, resulting in a unique biosynthetic pathway never reported in literature before. In the context of the novel pathway, dopamine was produced using tyramine as the intermediate compound. To achieve this, tyrosine was initially converted into tyramine by expressing TDC from Levilactobacillus brevis, which, in turn, was converted into dopamine through the action of the enzyme encoded by ppoMP from Mucuna pruriens. This marks the first time that an alternative biosynthetic pathway for dopamine has been validated in microbes. These findings underscore the effectiveness of our computational workflow in facilitating pathway enumeration and selection, offering the potential to uncover novel biosynthetic routes, thus paving the way for other target compounds of biotechnological interest.

Association of dysphagia severity in multiple system atrophy with the specific binding ratio on dopamine transporter SPECT.

OBJECTIVE: Dysphagia in multiple system atrophy (MSA) is life-threatening and is caused by parkinsonism with cerebellar ataxia as a contributing factor. The present study investigated the relationship between dysphagia severity in MSA and the specific binding ratio (SBR) on dopamine transporter (DaT) SPECT using the Hyodo score, a qualitative scale for use with fiberoptic endoscopic evaluation of swallowing (FEES). METHODS: Hyodo score's ability to predict aspiration during a FEES examination of 88 patients with MSA was first tested. Then the clinical characteristics, Hyodo score, and SBR of patients with either predominant parkinsonism (MSA-P; n = 11) or cerebellar ataxia (MSA-C; n = 25) who underwent FEES and DaT SPECT simultaneously were compared. RESULTS: Logistic regression demonstrated that the Hyodo score was a significant predictive factor of aspiration (p = 0.003). The MSA-P group had a significantly higher Hyodo score (p = 0.026) and lower SBR (p = 0.011) than the MSA-C group while neither group demonstrated any significant difference in disease duration at the FEES examination. Linear regression demonstrated a significant, inverse correlation between the Hyodo score and SBR in the MSA-P (p = 0.044; r = -0.616) and MSA-C (p = 0.044; r = -0.406) groups. When the effect of SBR was removed by analysis of covariance, no significant difference in the Hyodo score remained between the groups. CONCLUSIONS: Our results suggested an association between presynaptic changes in nigrostriatal dopaminergic neurons and dysphagia severity in MSA which largely contributes to the difference in dysphagia severity between MSA-P and MSA-C.