RESUMO
Pleistocene glaciations dramatically affected species distribution in regions that were impacted by ice cover and subsequent postglacial range expansion impacted contemporary biodiversity in complex ways. The European whitefish, Coregonus lavaretus, is a widely distributed salmonid fish species on mainland Europe, but in Britain it has only seven native populations, all of which are found on the western extremes of the island. The origins and colonization routes of the species into Britain are unknown but likely contributed to contemporary genetic patterns and regional uniqueness. Here, we used up to 25,751 genome-wide polymorphic loci to reconstruct the history and to discern the demographic and evolutionary forces underpinning divergence between British populations. Overall, we found lower genetic diversity in Scottish populations but high differentiation (FST = 0.433-0.712) from the English/Welsh and other European populations. Differentiation was elevated genome-wide rather than in particular genomic regions. Demographic modelling supported a postglacial colonization into western Scotland from northern refugia and a separate colonization route for the English/Welsh populations from southern refugia, with these two groups having been separated for more than ca. 50 Ky. We found cyto-nuclear discordance at a European scale, with the Scottish populations clustering closely with Baltic population in the mtDNA analysis but not in the nuclear data, and with the Norwegian and Alpine populations displaying the same mtDNA haplotype but being distantly related in the nuclear tree. These findings suggest that neutral processes, primarily drift and regionally distinct pre-glacial evolutionary histories, are important drivers of genomic divergence in British populations of European whitefish. This sheds new light on the establishment of the native British freshwater fauna after the last glacial maximum.
Assuntos
Variação Genética , Salmonidae , Animais , Evolução Biológica , DNA Mitocondrial/genética , Haplótipos , Filogenia , Salmonidae/genéticaRESUMO
Dementia is one of the most disabling non-motor symptoms in Parkinson's disease (PD). Unlike in Alzheimer's disease, the vascular pathology in PD is less documented. Due to the uncertain role of commonly investigated metabolic or vascular factors, e.g., hypertension or diabetes, other factors corresponding to PD dementia have been proposed. Associated dysautonomia and dopaminergic treatment seem to have an impact on diurnal blood pressure (BP) variability, which may presumably contribute to white matter hyperintensities (WMH) development and cognitive decline. We aim to review possible vascular and metabolic factors: Renin-angiotensin-aldosterone system, vascular endothelial growth factor (VEGF), hyperhomocysteinemia (HHcy), as well as the dopaminergic treatment, in the etiopathogenesis of PD dementia. Additionally, we focus on the role of polymorphisms within the genes for catechol-O-methyltransferase (COMT), apolipoprotein E (APOE), vascular endothelial growth factor (VEGF), and for renin-angiotensin-aldosterone system components, and their contribution to cognitive decline in PD. Determining vascular risk factors and their contribution to the cognitive impairment in PD may result in screening, as well as preventive measures.
Assuntos
Disfunção Cognitiva/fisiopatologia , Doença de Parkinson/fisiopatologia , Apolipoproteínas E/genética , Pressão Arterial/fisiologia , Catecol O-Metiltransferase/genética , Catecol O-Metiltransferase/metabolismo , Disfunção Cognitiva/sangue , Humanos , Hiper-Homocisteinemia/metabolismo , Hiper-Homocisteinemia/fisiopatologia , Doença de Parkinson/sangue , Sistema Renina-Angiotensina/fisiologia , Fatores de Risco , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/fisiologia , Substância Branca/patologiaRESUMO
Dementia in advanced Parkinson's Disease (PD) is a fatal milestone resulting in reduced life expectancy and nursing home placement. Cognitive impairment and cardiovascular dysautonomia are common and debilitating non-motor symptoms that frequently coexist in PD since the early stages and progress in subsequent years. In particular, blood pressure (BP) abnormalities, including orthostatic hypotension (OH), supine hypertension (SH) and the loss of nocturnal BP fall (non-dipping) in PD have been associated with cognitive deterioration. They usually have multifactorial aetiology, including neuronal (central and peripheral) mechanisms and concomitant intake of medications. BP abnormalities can influence cognition in many ways, including repeated cerebral hypoperfusion leading to cerebral ischaemic lesions, higher burden of white matter hyperintensities, and possible impact on neurodegenerative process in PD. They are often asymptomatic and remain unrecognised, hence 24-hour ambulatory BP monitoring is recommended in patients with clinical symptoms of dysautonomia. Management is challenging and should address the multifactorial nature of BP disturbances. The aim of this review was to present the state of current knowledge regarding the possible relationship between cardiovascular dysautonomia and cognition in PD, its diagnosis and treatment.
Assuntos
Hipotensão Ortostática , Doença de Parkinson , Disautonomias Primárias , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Cognição , Humanos , Doença de Parkinson/complicações , Disautonomias Primárias/etiologiaRESUMO
INTRODUCTION: Huntington's Disease (HD) is a neurodegenerative disorder of which the main symptoms are motor, cognitive and behavioural problems sometimes including sexual dysfunction. AIM: To review the current knowledge on sexual dysfunction in HD. METHODS: Databases of Pubmed and Scopus were searched. Only original studies performed after 1994 were included (from 1994 a genetic test = proven diagnosis). RESULTS: 162 publications were found, but only nine met our established criteria. The majority of patients with HD suffer from sexual disorders. The most common are: hypoactive sexual disorder (53-83% of patients), hyperactive sexual disorder (6-30%), erectile (48-74%) and ejaculatory dysfunctions (30-65%), lubrication problems (53-83%), and orgasmic dysfunction (35-78%). DISCUSSION: Results may be biased for several reasons e.g.: social taboos regarding sex lives, medications that affect sexual function, impaired self-awareness of patients, small study samples, a lack of standardised questionnaires, and a focus only on the presence of sexual problems without describing them. CONCLUSIONS: Sexual disorders in HD are common. This is a problem that is probably underestimated, both by patients/caregivers and physicians, who should focus more on these symptoms in order to improve patient quality of life.
Assuntos
Doença de Huntington , Disfunções Sexuais Fisiológicas , Disfunções Sexuais Psicogênicas , Humanos , Masculino , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
The prevalence of neurodegenerative diseases (NDs) is increasing due to the aging population and improved longevity. They are characterized by a range of pathological hallmarks, including protein aggregation, mitochondrial dysfunction, and oxidative stress. The aim of this review is to summarize the alterations in brain energy and amino acid metabolism in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Based on our findings, we proposed a group of selected metabolites related to disturbed energy or mitochondrial metabolism as potential indicators or predictors of disease. We also discussed the hidden challenges of metabolomics studies in NDs and proposed future directions in this field. We concluded that biochemical parameters of brain energy metabolism disruption (obtained with metabolomics) may have potential application as a diagnostic tool for the diagnosis, prediction, and monitoring of the effectiveness of therapies for NDs. However, more studies are needed to determine the sensitivity of the proposed candidates. We suggested that the most valuable biomarkers for NDs studies could be groups of metabolites combined with other neuroimaging or molecular techniques. To attain clinically applicable results, the integration of metabolomics with other "omic" techniques might be required.
RESUMO
BACKGROUND: After more than 2 years of the pandemic, effective treatment for COVID-19 is still under research. In recent months, publications hypothesized amantadine's potential beneficial effect on SARS-CoV-2 infection. OBJECTIVE: To compare the groups of Parkinson's Disease (PD) patients who were administered amantadine chronically and those who did not take this medication in the context of the incidence and severity of COVID-19 infection. METHODS: An observational, retrospective, multicenter cohort study was conducted among consecutive patients with idiopathic PD. The structured questionnaires were completed during the patient's follow-up visits at the Outpatient Clinic or during hospitalization. The questionnaire included the following informations: patient's age, duration of PD, Hoehn-Yahr (H-Y) stage, comorbidities, medications, COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR) swab test for SARS-CoV-2 with specified symptoms and their severity (home or hospital treatment). The vaccination status was verified as well. RESULTS: Five hundred fifty-two (n = 552) patients participated in the study - 329 men (60%). The mean H-Y stage was 2.44 (range: 1-4) and the mean duration of PD was 9.6 years (range: 1-34). One hundred four subjects (19%) had confirmed COVID-19 infection. Subjects over 50 years of age had a significantly lower incidence of COVID-19 (17% vs 38%, p = 0.0001) with difference also in mean H-Y stage (2.27 vs 2.49; p = 0.011) and disease duration (8.4 vs 9.9 years, p = 0.007). There were no differences between patients with and without co-morbidities. In the whole analyzed group 219 (40%) subjects were treated with amantadine. Comparing COVID-19 positive and negative patients, amantadine was used by 48/104 (46%) and 171/448 (38%) respectively. 22% of patients on amantadine vs. 17% of patients without amantadine developed COVID-19. These differences were not significant. There were no differences in morbidity and severity of COVID-19 between amantadine users and non-users as well. CONCLUSIONS: COVID-19 was less common in older (>50) with longer duration and more advanced patients. Amantadine did not affect the risk of developing COVID-19 or the severity of infection.