Autonomic dysfunction in Parkinson disease and animal models

Metzger, Jeanette M.; Emborg, Marina E.

doi:10.1007/s10286-018-00584-7

Cited by 34 publications

(37 citation statements)

References 199 publications

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“…These neurotoxins alter mitochondrial function in DA neurons and increase oxidative stress and neuroinflammation 21 , 22 . Toxin-induced models are invaluable in studying certain aspects of the disease and some of the findings on vascular damage and BBB leakage have been shown in these models 23 – 25 , however, these models rarely form α-syn aggregates 26 – 28 , and only partially reflect the age-dependent slowly progressive nature of the PD pathology 29 .…”

Section: Introductionmentioning

confidence: 99%

Human α-synuclein overexpression in a mouse model of Parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation

Elabi

Gaceb

Carlsson

et al. 2021

Sci Rep

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The pathological hallmark of Parkinson’s disease (PD) is the formation of Lewy bodies containing aggregated alpha-synuclein (α-syn). Although PD is associated with these distinct histological changes, other pathological features such as microvascular alterations have been linked to neurodegeneration. These changes need to be investigated as they create a hostile brain microenvironment and may contribute to the development and progression of the disease. We use a human α-syn overexpression mouse model that recapitulates some of the pathological features of PD in terms of progressive aggregation of human α-syn, impaired striatal dopamine fiber density, and an age-dependent motor deficit consistent with an impaired dopamine release. We demonstrate for the first time in this model a compromised blood–brain barrier integrity and dynamic changes in vessel morphology from angiogenesis at earlier stages to vascular regression at later stages. The vascular alterations are accompanied by a pathological activation of pericytes already at an early stage without changing overall pericyte density. Our data support and further extend the occurrence of vascular pathology as an important pathophysiological aspect in PD. The model used provides a powerful tool to investigate disease-modifying factors in PD in a temporal sequence that might guide the development of new treatments.

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Section: Introductionmentioning

confidence: 99%

Human α-synuclein overexpression in a mouse model of Parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation

Elabi

Gaceb

Carlsson

et al. 2021

Sci Rep

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“…Autonomic dysfunctions have incited great clinical interest since they frequently appear as PD nonmotor symptoms, afflicting up to 90% of PD individuals and imposing considerable burden in terms of morbimortality [ 7 ]. Autonomic dysfunctions may precede the onset of motor symptoms, and signs of cardiovascular dysautonomia commonly occur in PD patients [ 8 , 9 ]. Recently, a prospective epidemiological study revealed the association between reduced HRV measures in subjects without PD and augmented risk of developing the disease [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Propolis as a Potential Disease-Modifying Strategy in Parkinson’s disease: Cardioprotective and Neuroprotective Effects in the 6-OHDA Rat Model

et al. 2020

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Patients with Parkinson’s disease (PD) manifest nonmotor and motor symptoms. Autonomic cardiovascular dysregulation is a common nonmotor manifestation associated with increased morbimortality. Conventional clinical treatment alleviates motor signs but does not change disease progression and fails in handling nonmotor features. Nutrition is a key modifiable determinant of chronic disease. This study aimed to assess the effects of propolis on cardiological features, heart rate (HR) and heart rate variability (HRV) and on nigrostriatal dopaminergic damage, detected by tyrosine hydroxylase (TH) immunoreactivity, in the 6-hydroxydopamine (6-OHDA) rat model of PD. Male Wistar rats were injected bilaterally with 6-OHDA or saline into the striatum and were treated with propolis or water for 40 days. Autonomic function was assessed by time domain parameters (standard deviation of all normal-to-normal intervals (SDNN) and square root of the mean of the squared differences between adjacent normal RR intervals (RMSSD)) of HRV calculated from electrocardiogram recordings. Reductions in HR (p = 1.47 × 10−19), SDNN (p = 3.42 × 10−10) and RMSSD (p = 8.2 × 10−6) detected in parkinsonian rats were reverted by propolis. Propolis attenuated neuronal loss in the substantia nigra (p = 5.66 × 10−15) and reduced striatal fiber degeneration (p = 7.4 × 10−5) in 6-OHDA-injured rats, which also showed significant weight gain (p = 1.07 × 10−5) in comparison to 6-OHDA-lesioned counterparts. Propolis confers cardioprotection and neuroprotection in the 6-OHDA rat model of PD.

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“…The distribution of LBs in the brain region was consistent with the diversity of clinical symptoms in PD patients. These patients first showed nonmotor symptoms, such as olfactory and sleep disorders, and subsequently exhibited motor symptoms at the later stage [17][18][19]. Although Braak found that the pathology of LBs gradually appeared from one brain region to another in PD patients, the frequent appearance of α-syn in specific brain areas, such as the SNc, remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson’s Disease: Synaptic Pathology and Neuronal Aging

et al. 2020

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The motor and nonmotor symptoms of PD involve several brain regions. However, whether α-syn pathology originating from the SNc can directly lead to the pathological changes in distant cerebral regions and induce PD-related symptoms remains unclear. Here, AAV9-synapsin-mCherry-human SNCA (A53T) was injected into the unilateral SNc of mice. Motor function and olfactory sensitivity were evaluated. Our results showed that AAV9-synapsin-mCherry-human SNCA was continuously expressed in SNc. The animals showed mild motor and olfactory dysfunction at 7 months after viral injection. The pathology in SNc was characterized by the loss of dopaminergic neurons accompanied by ER stress. In the striatum, hα-syn expression was high, CaMKβ-2 and NR2B expression decreased, and active synapses reduced. In the olfactory bulb, hα-syn expression was high, and aging cells in the mitral layer increased. The results suggested that hα-syn was transported in the striatum and OB along the nerve fibers that originated from the SNc and induced pathological changes in the distant cerebral regions, which contributed to the motor and nonmotor symptoms of PD.

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Autonomic dysfunction in Parkinson disease and animal models

Cited by 34 publications

References 199 publications

Human α-synuclein overexpression in a mouse model of Parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation

Human α-synuclein overexpression in a mouse model of Parkinson’s disease leads to vascular pathology, blood brain barrier leakage and pericyte activation

Propolis as a Potential Disease-Modifying Strategy in Parkinson’s disease: Cardioprotective and Neuroprotective Effects in the 6-OHDA Rat Model

Noncanonical Roles of hα-syn (A53T) in the Pathogenesis of Parkinson’s Disease: Synaptic Pathology and Neuronal Aging

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