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Cureus Apr 2024Among the patient population in Basrah, Iraq, prolactinoma is the most commonly found pituitary tumor. Impulse control disorders (ICDs) were reportedly associated with...
BACKGROUND
Among the patient population in Basrah, Iraq, prolactinoma is the most commonly found pituitary tumor. Impulse control disorders (ICDs) were reportedly associated with these patients being treated with cabergoline. This study aimed to assess the prevalence of ICDs in cabergoline-treated prolactinoma patients versus healthy, matched controls.
METHODS
This cross-sectional case-control study was conducted at the Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC) in Basrah, southern Iraq, from January 2023 to May 2023. It included 30 cabergoline-treated prolactinoma patients and 30 healthy, matched controls. The questionnaire for ICDs in Parkinson's disease was used as a screening tool. Following this, positively screened patients were evaluated using validated criteria accordingly to diagnose impulse control disorders.
RESULTS
The ICDs were diagnosed in nine (30%) cabergoline-treated prolactinoma patients versus two (6.7%) in control (p = 0.02). The most frequent ICD types were hypersexuality and binge eating, while no patient reported pathological gambling. Three patients reported multiple types of ICDs. The patients' sociodemographic characteristics, prolactinoma duration and size, and cabergoline dose did not correlate significantly with ICD diagnosis.
CONCLUSIONS
Treatment with cabergoline is associated with the development of ICDs. Therefore, clinicians should be aware of this disabling side effect to ensure its early detection and treatment.
PubMed: 38957818
DOI: 10.7759/cureus.58516 -
Parkinson's Disease 2024The aim of this study was to compare the Sniffin' Sticks 12-identification test (SIT-12), China-modified version of the SIT-12 test (Ch-SIT-12) and brief smell...
China's Modified Version of Sniffin' Sticks 12-Identification Test Used in Chinese Parkinson's Disease and Multiple System Patients: Comparison of Three Olfactory Testing Methods.
OBJECTIVES
The aim of this study was to compare the Sniffin' Sticks 12-identification test (SIT-12), China-modified version of the SIT-12 test (Ch-SIT-12) and brief smell identification test for Chinese (B-SITC) in Chinese population of Parkinson's disease (PD) and multiple system atrophy (MSA).
METHODS
36 patients with PD and 7 patients with MSA were enrolled in this study. Three olfactory testing methods (SIT-12, Ch-SIT-12, and B-SITC) were used to test the olfactory function in all participants. Furthermore, demographic and clinical data were collected.
RESULTS
There was no significant difference between three olfactory tests in patients with PD (B-SITC vs. SIT-12: =0.508; Ch-SIT-12 vs. B-SITC: =0.146; and SIT-12 vs. Ch-SIT-12: =0.375). Tremor-dominant (TD) subtypes have better olfactory function than akinetic-rigid dominant (ARD) subtypes when using Ch-SIT-12 (77.8% vs. 29.6%, =0.019) or B-SITC (55.6% vs. 14.8%, =0.026). There was a statistical difference between the PD and MSA using Ch-SIT-12 to test the olfactory function (=0.046).
CONCLUSIONS
Our results indicated that SIT-12, Ch-SIT-12 and B-SITC can be used for the detection of olfactory dysfunction in Chinese population of PD. TD subtypes may have better olfactory function than ARD subtypes. In addition, Ch-SIT-12 may be used to differentiate PD from MSA, but that should be confirmed in a larger population.
PubMed: 38957659
DOI: 10.1155/2024/3561881 -
Frontiers in Medicine 2024Mild cognitive impairment (MCI) is a heterogeneous condition definable as the intermediate clinical state between normal aging and dementia. As a pre-dementia condition,... (Review)
Review
Mild cognitive impairment (MCI) is a heterogeneous condition definable as the intermediate clinical state between normal aging and dementia. As a pre-dementia condition, there is a recent growing interest in the identification of non-invasive markers able to predict the progression from MCI to a more advanced stage of the disease. Previous evidence showed the close link between gut microbiota and neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's disease (PD). Conversely, the actual relationship between gut microbiota and MCI is yet to be clarified. In this work, we provide an overview about the current knowledge regarding the role of gut microbiota in the context of MCI, also assessing the potential for microbiota-targeted therapies. Through the review of the most recent studies focusing on this topic, we found evidence of an increase of Bacteroidetes at phylum level and Bacteroides at genus level in MCI subjects with respect to healthy controls and patients with AD. Despite such initial evidence, the definitive identification of a typical microbiota profile associated with MCI is still far from being achieved. These preliminary results, however, are growingly encouraging research on the role of gut microbiota modulation in improving the cognitive status of pre-dementia subjects. To date, few studies evaluated the role of probiotics in MCI subjects, and they showed favorable results, although still biased by small sample size, heterogeneity of study design and short follow-up.
PubMed: 38957302
DOI: 10.3389/fmed.2024.1410246 -
Frontiers in Neuroscience 2024The incidence of neurological disorders, particularly age-related neurodegenerative pathologies, exhibits an alarming upward trend, while current pharmacological... (Review)
Review
The incidence of neurological disorders, particularly age-related neurodegenerative pathologies, exhibits an alarming upward trend, while current pharmacological interventions seldom achieve curative outcomes. Despite their diverse clinical presentations, neurological diseases often share a common pathological thread: the aberrant accumulation of misfolded proteins within the endoplasmic reticulum (ER). This phenomenon, known as ER stress, arises when the cell's intrinsic quality control mechanisms fail to cope with the protein-folding burden. Consequently, misfolded proteins accumulate in the ER lumen, triggering a cascade of cellular stress responses. Recognizing this challenge, researchers have intensified their efforts over the past two decades to explore natural compounds that could potentially slow or even reverse these devastating pathologies. Flavonoids constitute a vast and heterogeneous class of plant polyphenols, with over 10,000 identified from diverse natural sources such as wines, vegetables, medicinal plants, and organic products. Flavonoids are generally divided into six different subclasses: anthocyanidins, flavanones, flavones, flavonols, isoflavones, and flavonols. The diverse family of flavonoids, featuring a common phenolic ring backbone adorned with varying hydroxyl groups and additional modifications, exerts its antioxidant activity by inhibiting the formation of ROS, as evidenced by research. Also, studies suggest that polyphenols such as flavonoids can regulate ER stress through apoptosis and autophagy. By understanding these mechanisms, we can unlock the potential of flavonoids as novel therapeutic agents for neurodegenerative disorders. Therefore, this review critically examines the literature exploring the modulatory effects of flavonoids on various steps of the ER stress in neurological disorders.
PubMed: 38957188
DOI: 10.3389/fnins.2024.1348151 -
Brain and Behavior Jul 2024High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor...
The protective effects of repetitive transcranial magnetic stimulation with different high frequencies on motor functions in MPTP/probenecid induced Parkinsonism mouse models.
BACKGROUND
High-frequency repeated transcranial magnetic stimulation (rTMS) stimulating the primary motor cortex (M1) is an alternative, adjunctive therapy for improving the motor symptoms of Parkinson's disease (PD). However, whether the high frequency of rTMS positively correlates to the improvement of motor symptoms of PD is still undecided. By controlling for other parameters, a disease animal model may be useful to compare the neuroprotective effects of different high frequencies of rTMS.
OBJECTIVE
The current exploratory study was designed to compare the protective effects of four common high frequencies of rTMS (5, 10, 15, and 20 Hz) and iTBS (a special form of high-frequency rTMS) and explore the optimal high-frequency rTMS on an animal PD model.
METHODS
Following high frequencies of rTMS application (twice a week for 5 weeks) in a MPTP/probenecid-induced chronic PD model, the effects of the five protocols on motor behavior as well as dopaminergic neuron degeneration levels were identified. The underlying molecular mechanisms were further explored.
RESULTS
We found that all the high frequencies of rTMS had protective effects on the motor functions of PD models to varying degrees. Among them, the 10, 15, and 20 Hz rTMS interventions induced comparable preservation of motor function through the protection of nigrostriatal dopamine neurons. The enhancement of brain-derived neurotrophic factor (BDNF), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT-2) and the suppression of TNF-α and IL-1β in the nigrostriatum were involved in the process. The efficacy of iTBS was inferior to that of the above three protocols. The effect of 5 Hz rTMS protocol was weakest.
CONCLUSIONS
Combined with the results of the present study and the possible side effects induced by rTMS, we concluded that 10 Hz might be the optimal stimulation frequency for preserving the motor functions of PD models using rTMS treatment.
Topics: Animals; Transcranial Magnetic Stimulation; Mice; Male; Disease Models, Animal; Probenecid; Parkinsonian Disorders; Mice, Inbred C57BL; Brain-Derived Neurotrophic Factor; Motor Cortex; Dopaminergic Neurons; Dopamine Plasma Membrane Transport Proteins; Interleukin-1beta; Substantia Nigra; Corpus Striatum; Vesicular Monoamine Transport Proteins; MPTP Poisoning; Motor Activity; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
PubMed: 38956819
DOI: 10.1002/brb3.3605 -
Military Medical Research Jul 2024
Topics: Parkinson Disease; Gastrointestinal Microbiome; Humans
PubMed: 38956717
DOI: 10.1186/s40779-024-00545-4 -
Acta Neuropathologica Communications Jul 2024The genetic architecture of Parkinson's disease (PD) is complex and multiple brain cell subtypes are involved in the neuropathological progression of the disease. Here...
The genetic architecture of Parkinson's disease (PD) is complex and multiple brain cell subtypes are involved in the neuropathological progression of the disease. Here we aimed to advance our understanding of PD genetic complexity at a cell subtype precision level. Using parallel single-nucleus (sn)RNA-seq and snATAC-seq analyses we simultaneously profiled the transcriptomic and chromatin accessibility landscapes in temporal cortex tissues from 12 PD compared to 12 control subjects at a granular single cell resolution. An integrative bioinformatic pipeline was developed and applied for the analyses of these snMulti-omics datasets. The results identified a subpopulation of cortical glutamatergic excitatory neurons with remarkably altered gene expression in PD, including differentially-expressed genes within PD risk loci identified in genome-wide association studies (GWAS). This was the only neuronal subtype showing significant and robust overexpression of SNCA. Further characterization of this neuronal-subpopulation showed upregulation of specific pathways related to axon guidance, neurite outgrowth and post-synaptic structure, and downregulated pathways involved in presynaptic organization and calcium response. Additionally, we characterized the roles of three molecular mechanisms in governing PD-associated cell subtype-specific dysregulation of gene expression: (1) changes in cis-regulatory element accessibility to transcriptional machinery; (2) changes in the abundance of master transcriptional regulators, including YY1, SP3, and KLF16; (3) candidate regulatory variants in high linkage disequilibrium with PD-GWAS genomic variants impacting transcription factor binding affinities. To our knowledge, this study is the first and the most comprehensive interrogation of the multi-omics landscape of PD at a cell-subtype resolution. Our findings provide new insights into a precise glutamatergic neuronal cell subtype, causal genes, and non-coding regulatory variants underlying the neuropathological progression of PD, paving the way for the development of cell- and gene-targeted therapeutics to halt disease progression as well as genetic biomarkers for early preclinical diagnosis.
Topics: Humans; Parkinson Disease; Neurons; Gene Regulatory Networks; Male; Female; alpha-Synuclein; Aged; YY1 Transcription Factor; Genome-Wide Association Study; Transcriptome; Single-Cell Analysis; Temporal Lobe; Middle Aged; Gene Expression Regulation; Multiomics
PubMed: 38956662
DOI: 10.1186/s40478-024-01803-1 -
BMC Microbiology Jul 2024
PubMed: 38956499
DOI: 10.1186/s12866-024-03404-3 -
Scientific Reports Jul 2024Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists...
Ferroptosis is an iron-dependent cell death form characterized by reactive oxygen species (ROS) overgeneration and lipid peroxidation. Myricetin, a flavonoid that exists in numerous plants, exhibits potent antioxidant capacity. Given that iron accumulation and ROS-provoked dopaminergic neuron death are the two main pathological hallmarks of Parkinson's disease (PD), we aimed to investigate whether myricetin decreases neuronal death through suppressing ferroptosis. The PD models were established by intraperitoneally injecting 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into rats and by treating SH-SY5Y cells with 1-methyl-4-phenylpyridinium (MPP), respectively. Ferroptosis was identified by assessing the levels of Fe, ROS, malondialdehyde (MDA), and glutathione (GSH). The results demonstrated that myricetin treatment effectively mitigated MPTP-triggered motor impairment, dopamine neuronal death, and α-synuclein (α-Syn) accumulation in PD models. Myricetin also alleviated MPTP-induced ferroptosis, as evidenced by decreased levels of Fe, ROS, and MDA and increased levels of GSH in the substantia nigra (SN) and serum in PD models. All these changes were reversed by erastin, a ferroptosis activator. In vitro, myricetin treatment restored SH-SY5Y cell viability and alleviated MPP-induced SH-SY5Y cell ferroptosis. Mechanistically, myricetin accelerated nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and subsequent glutathione peroxidase 4 (Gpx4) expression in MPP-treated SH-SY5Y cells, two critical inhibitors of ferroptosis. Collectively, these data demonstrate that myricetin may be a potential agent for decreasing dopaminergic neuron death by inhibiting ferroptosis in PD.
Topics: Ferroptosis; Animals; Flavonoids; Rats; Disease Models, Animal; Male; Reactive Oxygen Species; Dopaminergic Neurons; Humans; Parkinson Disease; Cell Line, Tumor; Iron; alpha-Synuclein; Rats, Sprague-Dawley; Glutathione; Lipid Peroxidation; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NF-E2-Related Factor 2
PubMed: 38956066
DOI: 10.1038/s41598-024-62910-6 -
Nature Communications Jul 2024Iron plays a fundamental role in multiple brain disorders. However, the genetic underpinnings of brain iron and its implications for these disorders are still lacking....
Iron plays a fundamental role in multiple brain disorders. However, the genetic underpinnings of brain iron and its implications for these disorders are still lacking. Here, we conduct an exome-wide association analysis of brain iron, measured by quantitative susceptibility mapping technique, across 26 brain regions among 26,789 UK Biobank participants. We find 36 genes linked to brain iron, with 29 not being previously reported, and 16 of them can be replicated in an independent dataset with 3,039 subjects. Many of these genes are involved in iron transport and homeostasis, such as FTH1 and MLX. Several genes, while not previously connected to brain iron, are associated with iron-related brain disorders like Parkinson's (STAB1, KCNA10), Alzheimer's (SHANK1), and depression (GFAP). Mendelian randomization analysis reveals six causal relationships from regional brain iron to brain disorders, such as from the hippocampus to depression and from the substantia nigra to Parkinson's. These insights advance our understanding of the genetic architecture of brain iron and offer potential therapeutic targets for brain disorders.
Topics: Humans; Iron; Brain; Exome Sequencing; Male; Female; Mendelian Randomization Analysis; Genome-Wide Association Study; Parkinson Disease; Middle Aged; Genetic Predisposition to Disease; Aged; Nerve Tissue Proteins; Adult; Alzheimer Disease
PubMed: 38956042
DOI: 10.1038/s41467-024-49702-2