Alpha-synuclein-induced stress sensitivity renders the Parkinson’s disease brain susceptible to neurodegeneration

Acta Neuropathologica Communications, Год журнала: 2024, Номер 12(1)

Опубликована: Июнь 17, 2024

Abstract A link between chronic stress and Parkinson’s disease (PD) pathogenesis is emerging. Ample evidence demonstrates that the presynaptic neuronal protein alpha-synuclein (asyn) closely tied to PD pathogenesis. However, it not known whether system dysfunction present in PD, if asyn involved, if, together, they contribute neurodegeneration. To address these questions, we assess axis function transgenic rats overexpressing full-length wildtype human (asyn BAC rats) perform multi-level phenotyping following corticosterone administration. Stress signaling, namely corticotropin-releasing factor, glucocorticoid mineralocorticoid receptor gene expression, also examined post-mortem patient brains. Overexpression of leads HPA dysregulation rats, while administration significantly aggravates nigrostriatal degeneration, serine129 phosphorylated (pS129) expression neuroinflammation, leading phenoconversion from a prodromal an overt motor phenotype. Interestingly, induces robust, twofold increase pS129 hypothalamus, master regulator response, hippocampus, both target elevated levels altered markers signalling. Finally, defective hippocampal signalling mirrored brains correlates with levels. Taken our results brain provide circulating glucocorticoids can asyn-induced neurodegeneration, ultimately triggering PD.

Язык: Английский

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Psychological stress associated with prognostic uncertainties in recently diagnosed Parkinson’s disease patients: A qualitative study

PLoS ONE, Год журнала: 2025, Номер 20(3), С. e0319576 - e0319576

Опубликована: Март 11, 2025

Background Parkinson’s disease (PD) is a common neurodegenerative disorder that negatively impacts thousands of patients in Canada. The unexpected nature PD associated with decline mental health. highest level psychological stress occurs during the early years following diagnosis. Objectives To understand prognostic uncertainties recently diagnosed patients, uncover gaps current support systems, and recommend areas for improvement services aim to decrease receiving Methods An exploratory qualitative study was conducted using semi-structured interviews 13 more than 6 months less 5 years. Participants were recruited from Toronto Western Hospital Movement Disorders Clinic, Toronto, Ontario, Canada until saturation key themes reached. Results Five major identified capturing lived experiences diagnosis: 1) circumstances diagnosis its impact on 2) intrapersonal factors journey, 3) role social relationships patient’s life, 4) interaction different elements healthcare system, 5) available patients. Conclusions This uncovers burden faced by due insufficient systems. It emphasizes importance patient-centered approach improving their quality life through personalized services.

Язык: Английский

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DRN-SNc serotonergic circuit drives stress-induced motor deficits and Parkinson’s disease vulnerability

Neuropsychopharmacology, Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

Язык: Английский

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Study protocol for the MIND-PD study: a randomized controlled trial to investigate clinical and biological effects of mindfulness-based cognitive therapy in people with Parkinson’s disease

BMC Neurology, Год журнала: 2024, Номер 24(1)

Опубликована: Июнь 25, 2024

Abstract Background People with Parkinson’s disease (PD) are very sensitive to the effects of stress. The prevalence stress-related neuropsychiatric symptoms is high, and acute stress worsens motor symptoms. Animal studies suggest that chronic may accelerate progression, but evidence for this in humans lacking. Mindfulness-based interventions (MBIs) train participants focus on present moment, purpose without judgement. Previous MBIs alleviate reduce depression anxiety PD. We aim demonstrate efficacy Mindfulness-Based Cognitive Therapy (MBCT) as a non-pharmacologic treatment strategy (and motor) PD, identify mechanisms underlying reduction Methods In prospective randomized controlled trial (RCT), we investigate whether 8 weeks MBCT, compared care usual, can people include 124 PD patients, who experience mild-moderate depression, eligible magnetic resonance imaging (MRI) naïve mindfulness, have duration ≤ 10 years. Every participant followed 12 months. Clinical biochemical assessments take place at baseline (T0), after 2 months (T1), (T2); MRI T0 T2. Our primary outcome total score Hospital Anxiety Depression Scale (HADS) T1, while correcting HADS T0, age, gender. Beyond testing MBCT explore MBCT: (1) has an effect symptom severity, (2) influences cerebral markers stress, (3) leads change biomarkers progression. Discussion MIND-PD one first RCTs 1-year follow-up possible Insight into these pave way new methods future. Trial registration ClinicalTrials.gov, NCT05779137. Registered January 2023.

Язык: Английский

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Evidence for a causal-mechanistic role for positive appraisal style in stress resilience

Опубликована: Май 20, 2024

Stress resilience is the maintenance of mental health despite adversity. We have predicted that a tendency to appraise stressors in realistic slightly unrealistically positive fashion (positive appraisal style, PAS) prospectively associated with more resilient outcomes; PAS proximal and integrative factor, mediating pro-resilience effects other protective factors (e.g., social support); modifiable, changes leading corresponding resilience. In two independent observational samples (N=132 N=1034), we find predict over three years mediate support. Analyzing multi-component intervention (N=232) targets broad set factors, increases this mediates intervention-induced This establishes as plastic factor likely causal on

Язык: Английский

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The MIND-PD study: a randomized controlled trial to investigate clinical and biological effects of Mindfulness-Based Cognitive Therapy in people with Parkinson’s disease

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Июнь 26, 2024

Background People with Parkinson’s disease (PD) are very sensitive to the effects of stress. The prevalence stress-related neuropsychiatric symptoms is high, and acute stress worsens motor symptoms. Animal studies suggest that chronic may accelerate progression, but evidence for this in humans lacking. Mindfulness-based interventions (MBIs) train participants focus on present moment, purpose without judgement. Previous MBIs alleviate reduce depression anxiety PD. We aim demonstrate efficacy Mindfulness-Based Cognitive Therapy (MBCT) as a non-pharmacologic treatment strategy (and motor) PD, identify mechanisms underlying reduction Methods In prospective randomized controlled trial (RCT), we investigate whether 8 weeks MBCT, compared care usual, can people include 124 PD patients, who experience mild-moderate depression, eligible magnetic resonance imaging (MRI) naïve mindfulness, have duration ≤ 10 years. Every participant followed 12 months. Clinical biochemical assessments take place at baseline (T0), after 2 months (T1), (T2); MRI T0 T2. Our primary outcome total score Hospital Anxiety Depression Scale (HADS) T1, while correcting HADS T0, age, gender. Beyond testing MBCT explore MBCT: (1) has an effect symptom severity, (2) influences cerebral markers stress, (3) leads change biomarkers progression. Discussion MIND-PD one first RCTs 1-year follow-up possible Insight into these pave way new methods future. Trial registration: ClinicalTrials.gov, NCT05779137. Registered January 2023.

Язык: Английский

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Experiences of Living With the Nonmotor Symptoms of Parkinson's Disease: A Photovoice Study

Health Expectations, Год журнала: 2024, Номер 27(3)

Опубликована: Июнь 1, 2024

Nonmotor symptoms (NMSs) are frequently experienced by people with Parkinson's disease (PD) and often perceived as their most bothersome symptoms. However, these remain poorly understood suboptimal clinical management. These unmet needs an important determinant of health-related quality life (QoL) in PD.

Язык: Английский

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Survey on Parkinson’s Disease Diagnosis Impact: Patients, Caregivers and Health Care Professionals’ Perspectives

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(14), С. 4118 - 4118

Опубликована: Июль 14, 2024

Background: The announcement of Parkinson’s disease (PD) diagnosis may provoke negative feelings that impact the ability to cope with and all life changes related this new condition. There are scarce data on how improve communication about PD which factors influence outcome. Methods: We performed a national French survey, investigating large population people living (PwPD), who recently received (≤1 year since diagnosis), caregivers health care professionals (HCPs), from tertiary community-based hospitals. Results: A total 397 PwPD (45% female 82% > 50 years old), 192 120 HCPs (69% neurologists) completed questionnaire. was not expected by 60% induced in majority (82%) them. Negative experience moment were male gender [OR = 2.034, CI 95% 1.09–3.78; p 0.025] older age 1.05, 1.01–1.08; 0.004], while tremor as first symptom had threshold significance 1.78, 0.994–3.187; 0.052]. Half considered they did receive enough information one third short-term appointment rediscuss diagnosis. expressed willingness have multidisciplinary follow-up (PD nurse, psychologists). Only 24% been trained for announcement. Conclusions: way is delivered represents pivotal journey caregivers. This process requires improvement addressing gaps PwPD, caregivers, through participatory approach.

Язык: Английский

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The PRIME-NL study: evaluating a complex healthcare intervention for people with Parkinson’s disease in a dynamic environment

BMC Neurology, Год журнала: 2024, Номер 24(1)

Опубликована: Авг. 3, 2024

An innovative, integrative care model for people with Parkinson (PRIME Parkinson) has gradually been implemented in a selected region of the Netherlands since 2021. A prospective evaluation this (PRIME-NL study) was initiated parallel, spanning year prior to implementation (baseline) and period. Following publication original study protocol, COVID-19 crisis delayed full PRIME by two years hampered recruitment participants.

Язык: Английский

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A systematic review of the factors associated with the psychological wellbeing of people with Parkinson’s in the COVID-19 pandemic

Disability and Rehabilitation, Год журнала: 2024, Номер unknown, С. 1 - 12

Опубликована: Сен. 11, 2024

The lockdown and social distancing measures introduced as a result of the COVID-19 pandemic impacted ability people with Parkinson's to engage in normal health management practices. This led documented reductions psychological wellbeing. aim present review was identify factors associated wellbeing during acute stage pandemic.

Язык: Английский

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