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Brain Sciences Jun 2024Schizophrenia is a mental disorder affecting approximately 0.32% of the global population, according to the World Health Organization. Antipsychotic medications are used...
BACKGROUND
Schizophrenia is a mental disorder affecting approximately 0.32% of the global population, according to the World Health Organization. Antipsychotic medications are used to treat this condition by inhibiting D2 dopamine and 5HT2 serotonin receptors. The selection of the appropriate mode of delivery for these drugs is based on factors such as patient adherence, clinical presentation, and patient preferences. However, additional drivers of treatment selection are required in clinical practice. Mounting evidence suggests that neuroinflammation plays a crucial role in the pathogenesis of schizophrenia. NLR, a cost-effective biomarker of inflammation, has increased in several psychiatric conditions and may represent a valid method for studying the inflammatory stage in schizophrenia, relapse, and the first episode of psychosis. The aim of this study is to evaluate whether there are any variations in NLR values between patients given oral antipsychotics and those given long-acting antipsychotics.
METHODS
The study included 50 individuals with schizophrenia, either acute or in the follow-up phase. NLR was obtained by calculating the ratio of absolute neutrophil count (cells/μL) and absolute lymphocyte count (cells/μL).
RESULTS
Patients on long-acting antipsychotics exhibited significantly lower mean NLR scores (1.5 ± 0.7) compared to those on oral antipsychotics (2.2 ± 1.3) ( < 0.05).
CONCLUSIONS
NLR appears promising as a neuroinflammatory biomarker. This study reveals significantly lower NLR values in patients on long-acting antipsychotics, which may signify reduced systemic inflammation and improved adherence.
PubMed: 38928602
DOI: 10.3390/brainsci14060602 -
Brain Sciences May 2024The utility of transcranial sonography (TCS) remains unclarified for the auxiliary diagnosis of Parkinson's disease (PD). We investigated iodine-123...
The utility of transcranial sonography (TCS) remains unclarified for the auxiliary diagnosis of Parkinson's disease (PD). We investigated iodine-123 metaiodobenzylguanidine (MIBG) and TCS during the examination and diagnosis of high-signal-intensity substantia nigra lesion (HSI-SNL) incidence in PD patients previously diagnosed with dopamine transporter scintigraphy (DAT). The subjects were 67 patients with definitively diagnosed PD after DAT evaluation. Patients with midbrain substantia nigra visible during TCS who previously underwent MIBG were analyzed. The SN+ group comprised patients with extensive pathological HSI-SNL of Okawa class III/IV observed during TCS. The MIBG+ group comprised patients with a heart-to-mediastinum ratio of ≤2.2 during MIBG. TCS was performed to divide patients into the SN+ and SN- groups, and patient characteristics and MIBG findings were compared between the groups. PD was definitively diagnosed in 67 patients, among whom midbrain was visualized during TCS in 43 (64.1%) patients and pathological HSI-SNL was observed in 24 (35.8%). The MIBG findings were normal in six patients (27.3%) with HSI-SNL, and abnormal in seven (63.6%) without HSI-SNL. No significant differences were noted by Okawa classification in clinical characteristics based on the presence or absence of HSI-SNL. Multiple patients with normal findings during MIBG may have HSI-SNL. Thus, confirmatory imaging of HSI-SNL with TCS may be useful for diagnosis.
PubMed: 38928525
DOI: 10.3390/brainsci14060524 -
International Journal of Molecular... Jun 2024This study aimed to assess the expression profile of messenger RNA (mRNA) and microRNA (miRNA) related to the dopaminergic system in five types of breast cancer in...
This study aimed to assess the expression profile of messenger RNA (mRNA) and microRNA (miRNA) related to the dopaminergic system in five types of breast cancer in Polish women. Patients with five breast cancer subtypes were included in the study: luminal A ( = 130), luminal B ( = 196, including HER2-, = 100; HER2+, = 96), HER2+ ( = 36), and TNBC ( = 43); they underwent surgery, during which tumor tissue was removed along with a margin of healthy tissue (control material). The molecular analysis included a microarray profile of mRNAs and miRNAs associated with the dopaminergic system, a real-time polymerase chain reaction preceded by reverse transcription for selected genes, and determinations of their concentration using enzyme-linked immunosorbent assay (ELISA). The conducted statistical analysis showed that five mRNAs statistically significantly differentiated breast cancer sections regardless of subtype compared to control samples; these were dopamine receptor 2 (), dopamine receptor 3 (), dopamine receptor 25 (), transforming growth factor beta 2 (), and caveolin 2 (). The predicted analysis showed that hsa-miR-141-3p can regulate the expression of and , whereas hsa-miR-4441 is potentially engaged in the expression regulation of and . In addition, the expression pattern of mRNA can also be regulated by has-miR-16-5p. The overexpression of DRD2 and DRD3, with concomitant silencing of DRD5 expression, confirms the presence of dopaminergic abnormalities in breast cancer patients. Moreover, these abnormalities may be the result of miR-141-3P, miR-16-5p, and miR-4441 activity, regulating proliferation or metastasis.
Topics: Humans; Female; MicroRNAs; Breast Neoplasms; Gene Expression Regulation, Neoplastic; Middle Aged; Dopamine; Adult; Gene Expression Profiling; Aged; RNA, Messenger; Receptors, Dopamine D3; Receptors, Dopamine D2; Transforming Growth Factor beta2
PubMed: 38928253
DOI: 10.3390/ijms25126546 -
International Journal of Molecular... Jun 2024Physiology and behavior are structured temporally to anticipate daily cycles of light and dark, ensuring fitness and survival. Neuromodulatory systems in the...
Physiology and behavior are structured temporally to anticipate daily cycles of light and dark, ensuring fitness and survival. Neuromodulatory systems in the brain-including those involving serotonin and dopamine-exhibit daily oscillations in neural activity and help shape circadian rhythms. Disrupted neuromodulation can cause circadian abnormalities that are thought to underlie several neuropsychiatric disorders, including bipolar mania and schizophrenia, for which a mechanistic understanding is still lacking. Here, we show that genetically depleting serotonin in knockout mice promotes manic-like behaviors and disrupts daily oscillations of the dopamine biosynthetic enzyme tyrosine hydroxylase (TH) in midbrain dopaminergic nuclei. Specifically, while TH mRNA and protein levels in the Substantia Nigra (SN) and Ventral Tegmental Area (VTA) of wild-type mice doubled between the light and dark phase, TH levels were high throughout the day in knockout mice, suggesting a hyperdopaminergic state. Analysis of TH expression in striatal terminal fields also showed blunted rhythms. Additionally, we found low abundance and blunted rhythmicity of the neuropeptide cholecystokinin (Cck) in the VTA of knockout mice, a neuropeptide whose downregulation has been implicated in manic-like states in both rodents and humans. Altogether, our results point to a previously unappreciated serotonergic control of circadian dopamine signaling and propose serotonergic dysfunction as an upstream mechanism underlying dopaminergic deregulation and ultimately maladaptive behaviors.
Topics: Animals; Serotonin; Mice; Mice, Knockout; Circadian Rhythm; Dopamine; Tyrosine 3-Monooxygenase; Tryptophan Hydroxylase; Ventral Tegmental Area; Cholecystokinin; Dopaminergic Neurons; Male; Substantia Nigra; Mice, Inbred C57BL; Bipolar Disorder
PubMed: 38928178
DOI: 10.3390/ijms25126475 -
International Journal of Molecular... Jun 2024It seems that BDNF has a direct influence on the brain pathways and is typically engaged during the processing of rewards. A surge in BDNF levels in the ventral...
It seems that BDNF has a direct influence on the brain pathways and is typically engaged during the processing of rewards. A surge in BDNF levels in the ventral tegmental area (the region from which the dopaminergic neurons of the mesocorticolimbic dopamine system originate and extend to the dorsolateral and ventromedial striatum) triggers a state of reward similar to that produced by opiates in animal studies. The aims of the study were (1) to analyze the association of the gene rs6265 polymorphism with AUD (alcohol use disorder) in women, (2) analyze personality and anxiety in alcohol-dependent and control woman, and (3) conduct an interaction analysis of rs6265 on personality, anxiety, and alcohol dependence. Our study found a notable interaction between the anxiety (trait and state), neuroticism, rs6265, and AUD. The alcohol AUD G/A genotype carriers revealed higher level of the anxiety trait ( < 0.0001) and neuroticism ( < 0.0001) compared to the control group with G/A and G/G genotypes. The alcohol use disorder subjects with the G/A genotype displayed higher levels of an anxiety state than the control group with G/A ( < 0.0001) and G/G ( = 0.0014) genotypes. Additionally, the alcohol use disorder subjects with the G/G genotype obtained lower levels of agreeability compared to the controls with G/A ( < 0.0001) and G/G ( < 0.0001) genotypes. Our study indicates that anxiety (trait and state) and neuroticism are interacting with the gene rs6265 polymorphism in alcohol-dependent women. Characteristics like anxiety (both as a trait and a state) and neuroticism could have a significant impact on the mechanism of substance dependency, particularly in females who are genetically susceptible. This is regardless of the reward system that is implicated in the emotional disruptions accompanying anxiety and depression.
Topics: Humans; Brain-Derived Neurotrophic Factor; Female; Alcoholism; Adult; Polymorphism, Single Nucleotide; Personality; Middle Aged; Anxiety; Genetic Predisposition to Disease; Genotype; Neuroticism; Case-Control Studies
PubMed: 38928154
DOI: 10.3390/ijms25126448 -
Genes Jun 2024Multiple sclerosis (MS) is a common chronic autoimmune disease of the central nervous system. In MS, disability progresses unpredictably. Dopamine (DA) is a modulator of...
BACKGROUND
Multiple sclerosis (MS) is a common chronic autoimmune disease of the central nervous system. In MS, disability progresses unpredictably. Dopamine (DA) is a modulator of immune functions, and compelling evidence supports its involvement in both pathogenesis and treatment of MS. Although single nucleotide polymorphisms (SNPs) in dopaminergic receptor (DR) genes have been extensively studied, their role in MS progression remains unexplored. Therefore, the aim of this explorative study is to investigate the potential association between functional SNPs in DR genes and MS progression.
METHODS
Caucasian patients with relapsing-remitting (RR) MS were enrolled, and disease progression assessed by the Multiple Sclerosis Severity Score (MSSS).
RESULTS
Out of the 59 RRMS patients enrolled, those with the G/G genotype for rs6280 and rs1800828 SNPs in DRD3 showed significantly higher MSSSs compared to those with ancestral and heterozygous genotypes.
CONCLUSIONS
If confirmed in a larger prospective study, the reported findings could contribute to a better understanding of MS pathophysiological mechanisms, opening the way for the identification of marker(s) for assessing MS progression as well as novel therapeutic strategies. A personalized approach to MS management has the potential to improve the overall well-being of MS patients and alleviate the burden on their caregivers.
Topics: Humans; Multiple Sclerosis, Relapsing-Remitting; Female; Male; Polymorphism, Single Nucleotide; Adult; Receptors, Dopamine D3; Disease Progression; Middle Aged; Genotype; Genetic Predisposition to Disease
PubMed: 38927672
DOI: 10.3390/genes15060736 -
Biomedicines Jun 2024This study aimed to test the hypothesis that the postactivation effect (PAE, involuntary normal muscle tone) is modified by dopaminergic mechanisms. The PAE was tested...
This study aimed to test the hypothesis that the postactivation effect (PAE, involuntary normal muscle tone) is modified by dopaminergic mechanisms. The PAE was tested with surface electromyography (sEMG) in the "off medication" phase in participants with Parkinson's disease (PD) and in the "on medication" state in participants with schizophrenia (SZ), which modeled hypodopaminegic conditions, and in participants with PD "on medication" (PD) and in participants with SZ "off medication" (SZ) state which modeled the hyperdopaminergic conditions. Healthy age-matched participants constituted the control group (HC, = 11). In hyperdopaminergic models, PAE was triggered in 71.3% of participants in SZ and in 35.7% in PD conditions. In the hypodopaminergic models, PAE was triggered in 12% in SZ and in 21.4% in PD conditions. In the HC group, PAE was present in 91% of participants. In the HC and PD groups, the mean frequency and correlation dimension of sEMG at PAE was higher than that during voluntary isometric contraction. In conclusion, in hypodopaminergic models, PAE triggering was inhibited. The manifestations and EMG characteristics of PAE in people with PD or SZ may indicate dopaminergic dysfunction.
PubMed: 38927545
DOI: 10.3390/biomedicines12061338 -
Biomedicines Jun 2024Playing a key role in the organization of striatal motor output, the dopamine (DA)-ergic system regulates both innate and complex learned behaviors. Growing evidence...
Playing a key role in the organization of striatal motor output, the dopamine (DA)-ergic system regulates both innate and complex learned behaviors. Growing evidence clearly indicates the involvement of the DA-ergic system in different forms of repetitive (perseverative) behavior. Some of these behaviors accompany such disorders as obsessive-compulsive disorder (OCD), Tourette's syndrome, schizophrenia, and addiction. In this study, we have traced how the inflexibility of repetitive reactions in the recently developed animal model of hyper-DA-ergia, dopamine transporter knockout rats (DAT-KO rats), affects the realization of innate behavior (grooming) and the learning of spatial (learning and reversal learning in T-maze) and non-spatial (extinction of operant reaction) tasks. We found that the microstructure of grooming in DAT-KO rats significantly differed in comparison to control rats. DAT-KO rats more often demonstrated a fixed syntactic chain, making fewer errors and very rarely missing the chain steps in comparison to control rats. DAT-KO rats' behavior during inter-grooming intervals was completely different to the control animals. During learning and reversal learning in the T-maze, DAT-KO rats displayed pronounced patterns of hyperactivity and perseverative (stereotypical) activity, which led to worse learning and a worse performance of the task. Most of the DAT-KO rats could not properly learn the behavioral task in question. During re-learning, DAT-KO rats demonstrated rigid perseverative activity even in the absence of any reinforcement. In operant tasks, the mutant rats demonstrated poor extinction of operant lever pressing: they continued to perform lever presses despite no there being reinforcement. Our results suggest that abnormally elevated DA levels may be responsible for behavioral rigidity. It is conceivable that this phenomenon in DAT-KO rats reflects some of the behavioral traits observed in clinical conditions associated with endogenous or exogenous hyper-DA-ergia, such as schizophrenia, substance abuse, OCD, patients with Parkinson disease treated with DA mimetics, etc. Thus, DAT-KO rats may be a valuable behavioral model in the search for new pharmacological approaches to treat such illnesses.
PubMed: 38927477
DOI: 10.3390/biomedicines12061270 -
Biomedicines Jun 2024Depression is a common mental illness of great concern. Current therapy for depression is only suitable for 80% of patients and is often associated with unwanted side... (Review)
Review
Depression is a common mental illness of great concern. Current therapy for depression is only suitable for 80% of patients and is often associated with unwanted side effects. In this regard, the search for and development of new antidepressant agents remains an urgent task. In this review, we discuss the current available evidence indicating that G protein-coupled trace amine-associated receptors (TAARs) might represent new targets for depression treatment. The most frequently studied receptor TAAR1 has already been investigated in the treatment of schizophrenia, demonstrating antidepressant and anxiolytic properties. In fact, the TAAR1 agonist Ulotaront is currently undergoing phase 2/3 clinical trials testing its safety and efficacy in the treatment of major depressive disorder and generalized anxiety disorder. Other members of the TAAR family (TAAR2, TAAR5, TAAR6, TAAR8, and TAAR9) are not only involved in the innate olfaction of volatile amines, but are also expressed in the limbic brain areas. Furthermore, animal studies have shown that TAAR2 and TAAR5 regulate emotional behaviors and thus may hold promise as potential antidepressant targets. Of particular interest is their connection with the dopamine and serotonin systems of the brain and their involvement in the regulation of adult neurogenesis, known to be affected by the antidepressant drugs currently in use. Further non-clinical and clinical studies are necessary to validate TAAR1 (and potentially other TAARs) as novel therapeutic targets for the treatment of depression.
PubMed: 38927470
DOI: 10.3390/biomedicines12061263 -
Biomedicines May 2024Graphitic carbon nitride (g-CN) is an intriguing nanomaterial that exhibits photoconductive fluorescence properties under UV-visible light. Dopamine (DA) coating of g-CN...
Graphitic carbon nitride (g-CN) is an intriguing nanomaterial that exhibits photoconductive fluorescence properties under UV-visible light. Dopamine (DA) coating of g-CN prepared from melamine was accomplished via self-polymerization of DA as polydopamine (PDA). The g-CN was coated with PDA 1, 3, and 5 times repeatedly as (PDA@g-CN) in tris buffer at pH 8.5. As the number of PDA coatings was increased on g-CN, the peak intensity at 1512 cm for N-H bending increased. In addition, the increased weight loss values of PDA@g-CN structures at 600 °C from TGA thermograms confirmed that the coating was accomplished. The band gap of g-CN, 2.72 eV, was reduced to 0.87 eV after five coatings with PDA. A pristine g-CN was found to have an isoelectric point (IEP) of 4.0, whereas the isoelectric points of 1PDA@g-CN and 3PDA@g-CN are close to each other at 3.94 and 3.91, respectively. On the other hand, the IEP of 5PDA@g-CN was determined at pH 5.75 assuming complete coating with g-CN. The biocompatibility of g-CN and PDA@g-CN against L929 fibroblast cell lines revealed that all PDA@g-CN coatings were found to be biocompatible up to a 1000 mg/mL concentration, establishing that PDA coatings did not adversely affect the biocompatibility of the composite materials. In addition, PDA@g-CN was screened for antioxidant potential via total phenol content (TPC) and total flavonoid content assays and it was found that PDA@g-CN has recognizable TPC values and increased linearly with an increased number of PDA coatings. Furthermore, blood compatibility of pristine g-CN is enhanced considerably upon PDA coating, affirmed by hemolysis and the blood clotting index%. Additionally, α-glucosidase inhibitory properties of PDA@g-CN structures revealed that 67.6 + 9.8% of this enzyme was evenly inhibited by 3PDA@g-CN structure.
PubMed: 38927358
DOI: 10.3390/biomedicines12061151