Navigating the Neurobiology of Parkinson's: The Impact and Potential of α-Synuclein.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide; therefore, since its initial description, significant progress has been made, yet a mystery remains regarding its pathogenesis and elusive root cause. The widespread distribution of pathological α-synuclein (αSyn) aggregates throughout the body raises inquiries regarding the etiology, which has prompted several hypotheses, with the most prominent one being αSyn-associated proteinopathy. The identification of αSyn protein within Lewy bodies, coupled with genetic evidence linking αSyn locus duplication, triplication, as well as point mutations to familial Parkinson's disease, has underscored the significance of αSyn in initiating and propagating Lewy body pathology throughout the brain. In monogenic and sporadic PD, the presence of early inflammation and synaptic dysfunction leads to αSyn aggregation and neuronal death through mitochondrial, lysosomal, and endosomal functional impairment. However, much remains to be understood about αSyn pathogenesis, which is heavily grounded in biomarkers and treatment strategies. In this review, we provide emerging new evidence on the current knowledge about αSyn's pathophysiological impact on PD, and its presumable role as a specific disease biomarker or main target of disease-modifying therapies, highlighting that this understanding today offers the best potential of disease-modifying therapy in the near future.

Effects of itaconic acid on neuronal viability and brain mitochondrial functions.

Recent studies have identified that under stimulation by bacterial lipopolysaccharide mammalian macrophages produce itaconic acid. Yet, it is unknown whether itaconate has any effect on viability of brain cells. Here we used extracellularly added itaconate to investigate its effects on viability of cerebellar granule cells (CGC) in cultures and respiratory functions of these cells and isolated brain mitochondria. We found that 3-5 mM itaconate had no effect on the viability of neurons, but 10 mM itaconate was toxic and induced neuronal apoptosis. Removal of itaconate after 24 h incubation resulted in further decrease in viability and number of neurons. Respiration of intact neurons was not affected by itaconate, but permeabilized cells as well as isolated brain mitochondria demonstrated decreased rates of respiration in the presence of itaconate. Using isolated adult rat brain mitochondria we found that itaconate decreased mitochondrial phosphorylating respiration, mitochondrial calcium retention capacity, production of reactive oxygen species with Complex I and Complex II substrates as well as inhibition of Complex I, Complex IV and ATP synthase. In conclusion, the results suggest that itaconic acid at millimolar concentrations affects mitochondrial functions and viability of neurons.

Ultrasonography of the Vagus Nerve in the Diagnosis of Parkinson's Disease.

BACKGROUND: It is currently impossible to diagnose Parkinson's disease (PD) in the premotor phase even though at the time of motor symptom onset the number of already degenerated dopaminergic substantia nigra neurons is considerable. Degeneration of the dorsal nucleus of the vagus nerve (VN) has been reported early in the disease course, and it could lead to impaired function of the VN, resulting in certain nonmotor symptoms of PD. Therefore, we raised a hypothesis that the loss of VN neurons could result in a smaller diameter of the VN among PD patients. METHODS: 20 PD patients and 20 age- and gender-matched individuals without any neurodegenerative disease were enrolled in a pilot study. The diameters of the right and left VNs were measured using ultrasonography, their average was calculated, and the narrower VN diameter was noted separately. RESULTS: No difference was found between the PD and control groups neither in the average VN diameter (mean 1.17; 95% confidence interval (CI) 1.10-1.24 vs. 1.13; 1.07-1.18, mm; p=0.353) nor in the narrower VN diameter (mean 1.11; 95% confidence interval (CI) 1.02-1.20 vs. 1.07; 1.02-1.13, mm; p=0.421). The narrower VN diameter and the average VN diameter were not able to distinguish between PD patients and controls (area under curve (AUC) = 0.588, 95% CI = 0.408-0.767, and p=0.344; and AUC = 0.578, 95% CI = 0.396-0.759, and p=0.402). CONCLUSIONS: To conclude, no differences were found in VN diameter between the PD and control groups. Therefore, our data do not support the hypothesis that PD could be associated with a smaller diameter of the VN.

Use of combined oral contraceptives and headaches.

OBJECTIVE: The study was designed to examine the certain patterns of combined oral contraceptive use in women of childbearing potential and evaluate the relationship between the use of combined oral contraceptives and headaches, bad habits, type of work, and concomitant diseases. MATERIAL AND METHODS: In total, 194 randomly selected women aged 18 to 40 years who visited a gynecologist for preventive gynecological examination were surveyed. Respondents were categorized as combined oral contraceptive users (n=116; study group) and nonusers (n=78; control group). An anonymous questionnaire developed by the authors of this study and a standardized scale called the Migraine Disability Assessment Scale (MIDAS) were used for the survey. RESULTS: A multivariate logistic regression analysis demonstrated a significantly higher prevalence of combined oral contraceptive use in women older than 20 years (odds ratio, 6.0; 95% CI, 2.6-14), better educated women (odds ratio, 5.7; 95% CI, 2.1-15.2), and women reporting a steady sexual partner (odds ratio, 4.0; 95% CI, 1.5-11.0). Relationship between headaches and use of combined oral contraceptives as well as other factors were analyzed in a group of 178 respondents; the rest 16 respondents reported not having headaches at all. The prevalence of reported minimal-to-mild and moderate-to-severe impact of headaches on daily activities did not differ significantly between the study and control groups, women with and without bad habits, and white-collar and blue-collar groups (P>0.05). However, women with concomitant diseases significantly more often reported moderate-to-severe impact on daily activities due to headaches (P<0.01). Differences in impact of headaches on daily activities between women using combined oral contraceptives containing 20 or less µg of ethinylestradiol and 30 or more µg of ethinylestradiol did not differ significantly. CONCLUSIONS: The prevalence of combined oral contraceptive use was higher in women older than 20 years, better educated women, and women reporting a steady sexual partner. The impact of headaches on daily activities did not differ significantly between the combined oral contraceptive users and nonusers.

Do the quality of health care services provided at personal health care institutions of Kaunas city and access to it meet expectations of pregnant women.

OBJECTIVES: To evaluate if the quality of services provided by family physicians and obstetricians/gynecologists at primary personal health care institutions of Kaunas city and access to it meet the needs and expectations of pregnant women. MATERIAL AND METHODS: Pregnant women visiting the selected health care institutions at their third trimester of pregnancy were asked to fill in the anonymous questionnaire. The study was conducted at two randomly selected maternity centers of Kaunas city and two family practices of Kaunas city where antenatal care was provided by family physicians. The questionnaires were given to 106 patients visiting family physicians (response rate was 88.7%) and to 202 patients visiting obstetricians/gynecologists (response rate was 81.7%). RESULTS: Health services provided by family physicians and obstetricians/gynecologists met the expectations of pregnant women in respect of providing with information and communication. The patients of obstetricians/gynecologists significantly more often stated that they were very satisfied with patient-physician communication (P<0.05), they significantly more often understood explanations given by the physician (P<0.001) and claimed having sufficient knowledge about pregnancy (P<0.05), while the patients of family physicians significantly more often asserted that the physician helped them in preparation for childbirth (P<0.05). The patients of obstetricians/gynecologists significantly more often did not face any problems with access to services as compared to the patients of family physicians (z=3.0). Most of pregnant women stated that they were satisfied or very satisfied with the quality of health care at the health care facility providing them with antenatal care irrespective of the physician's specialty. CONCLUSIONS: The quality of antenatal health care provided by both family physicians and obstetricians/gynecologists and access to it satisfied the needs and expectations of the surveyed women. Correction of the limitations noticed, e.g., closer communication, more understandable explanations, more attention to preparation for childbirth, better work planning, could improve the quality of antenatal care provided by the family physicians.