scholarly journals Loss of p21-activated kinase Mbt/PAK4 causes Parkinson-like phenotypes in Drosophila

2021 ◽  
Author(s):  
Stephanie M Pütz ◽  
Jette Kram ◽  
Elisa Rauh ◽  
Sophie Kaiser ◽  
Romy Toews ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Life Expectancy ◽  
Emotional Behavior ◽  
Stressful Situation ◽  
Causative Role ◽  
Motor Impairments ◽  
Age Dependent ◽  
Negative Effect ◽  
P21 Activated Kinase

Parkinson's disease (PD) provokes bradykinesia, resting tremor, rigidity and postural instability but also non-motor symptoms such as depression, anxiety, sleep and cognitive impairments. Similar phenotypes can be induced in Drosophila melanogaster through modification of PD-relevant genes or the administration of PD-inducing toxins. Recent studies correlated deregulation of human p21-activated kinase PAK4 with PD, leaving open the question of a causative relationship of mutations in this gene for manifestation of PD symptoms. To figure out whether flies lacking the PAK4 homolog Mushroom bodies tiny (Mbt) show PD-like phenotypes, we tested for a variety of PD criteria. Here we demonstrate that mbt mutant flies show PD-like phenotypes including age-dependent movement deficits, reduced life expectancy and fragmented sleep. They also react to a stressful situation with higher immobility, indicating an influence of Mbt on emotional behavior. Loss of Mbt function has a negative effect on the number of dopaminergic protocerebral anterior medial (PAM) neurons, most likely caused by a proliferation defect of neural progenitors. The age-dependent movement deficits are not accompanied by a corresponding further loss of PAM neurons. Previous studies highlighted the importance of a small PAM subgroup for age-dependent PD motor impairments. We show that impaired motor skills are caused by lack of Mbt in this PAM subgroup. In addition, a broader re-expression of Mbt in PAM neurons improves life expectancy. Conversely, selective Mbt knockout in the same cells shortens life span. We conclude that mutations in Mbt/PAK4 can play a causative role in the development of Parkinson's disease phenotypes.

scholarly journals Acute dopamine boost has a negative effect on plasticity of the primary motor cortex in advanced Parkinson's disease

Brain ◽  
2012 ◽  
Vol 135 (7) ◽  
pp. 2074-2088 ◽  
Author(s):  
A. Kishore ◽  
T. Popa ◽  
B. Velayudhan ◽  
T. Joseph ◽  
A. Balachandran ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Advanced Parkinson’S Disease ◽  
Negative Effect

scholarly journals Cav2.3 channels contribute to dopaminergic neuron loss in a model of Parkinson’s disease

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Julia Benkert ◽  
Simon Hess ◽  
Shoumik Roy ◽  
Dayne Beccano-Kelly ◽  
Nicole Wiederspohn ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Neuronal Viability ◽  
Age Dependent ◽  
Human Ipsc ◽  
Reduced Activity ◽  
Dopaminergic Neuron Loss ◽  
Full Protection

Abstract Degeneration of dopaminergic neurons in the substantia nigra causes the motor symptoms of Parkinson’s disease. The mechanisms underlying this age-dependent and region-selective neurodegeneration remain unclear. Here we identify Cav2.3 channels as regulators of nigral neuronal viability. Cav2.3 transcripts were more abundant than other voltage-gated Ca2+ channels in mouse nigral neurons and upregulated during aging. Plasmalemmal Cav2.3 protein was higher than in dopaminergic neurons of the ventral tegmental area, which do not degenerate in Parkinson’s disease. Cav2.3 knockout reduced activity-associated nigral somatic Ca2+ signals and Ca2+-dependent after-hyperpolarizations, and afforded full protection from degeneration in vivo in a neurotoxin Parkinson’s mouse model. Cav2.3 deficiency upregulated transcripts for NCS-1, a Ca2+-binding protein implicated in neuroprotection. Conversely, NCS-1 knockout exacerbated nigral neurodegeneration and downregulated Cav2.3. Moreover, NCS-1 levels were reduced in a human iPSC-model of familial Parkinson’s. Thus, Cav2.3 and NCS-1 may constitute potential therapeutic targets for combatting Ca2+-dependent neurodegeneration in Parkinson’s disease.

scholarly journals Editorial for the Special Issue “Animal Models of Parkinson’s Disease and Related Disorders”

2020 ◽  
Vol 21 (12) ◽  
pp. 4250
Author(s):  
Yuzuru Imai
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Motor Dysfunction ◽  
Special Issue ◽  
Midbrain Dopaminergic Neurons ◽  
Age Dependent ◽  
Common Neurodegenerative Disorder

Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by age-dependent motor dysfunction and degeneration of the midbrain dopaminergic neurons [...]

scholarly journals Paired-Pulse Inhibition in the Auditory Cortex in Parkinson's Disease and Its Dependence on Clinical Characteristics of the Patients

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Elena Lukhanina ◽  
Natalia Berezetskaya ◽  
Irina Karaban
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Auditory Cortex ◽  
Healthy Subjects ◽  
Clinical Characteristics ◽  
Auditory Evoked Potentials ◽  
Disease Onset ◽  
Paired Pulse ◽  
Age Dependent ◽  
State Examination

We aimed to determine the value of the paired-pulse inhibition (PPI) in the auditory cortex in patients with Parkinson's disease (PD) and analyze its dependence on clinical characteristics of the patients. The central (Cz) auditory evoked potentials were recorded in 58 patients with PD and 22 age-matched healthy subjects. PPI of the N1/P2 component was significantly(P<.001)reduced for interstimulus intervals 500, 700, and 900 ms in patients with PD compared to control subjects. The value of PPI correlated negatively with the age of the PD patients(P<.05), age of disease onset(P<.05), body bradykinesia score(P<.01), and positively with the Mini Mental State Examination (MMSE) cognitive score(P<.01). Negative correlation between value of PPI and the age of the healthy subjects(P<.05)was also observed. Thus, results show that cortical inhibitory processes are deficient in PD patients and that the brain's ability to carry out the postexcitatory inhibition is age-dependent.

MORTALITY IN PARKINSON'S DISEASE AND ATYPICAL PARKINSONIAN DISORDERS

2015 ◽  
Vol 86 (11) ◽  
pp. e4.88-e4
Author(s):  
Angus Macleod ◽  
Carl Counsell
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Life Expectancy ◽  
Median Survival ◽  
Lewy Body Dementia ◽  
Mortality Data ◽  
Kaplan Meier ◽  
Central Register ◽  
Population Mortality ◽  
Incident Cohort

BackgroundWe evaluated the mortality associated with Parkinson's disease (PD), Lewy body dementia (LBD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and vascular parkinsonism (VP) using a community-based incident cohort.MethodsAll incident parkinsonism cases identified over 4.5 years (2002-4, 2006-9) were tagged to the NHS central register for regular death notifications. Kaplan-Meier survival probabilities were plotted. Standardised mortality ratios (SMRs) and life expectancy, adjusted for age, sex and calendar year, were calculated using regional mortality data.ResultsUntil June 2014, 90 deaths occurred in 198 PD patients, and 107 deaths in 117 patients with other syndromes. Median survival in PD, LBD, PSP, MSA, and VP was 7.8 (6.7–9.4), 3.3 (2.3–4.1), 2.6 (1.1–3.8), 5.1 (1.3–NA), 2.1 (1.5–3.4) years, respectively. SMRs were 1.5 (1.2–1.9), 4.2 (3.0–5.9), 3.8 (2.6–5.5), 1.8 (0.9–3.4), 4.2 (3.0–6.0) respectively. In PD, median survival was lower than life expectancy, but more so in under 65s.ConclusionsMortality in PD was increased by 50% over expected population mortality. Younger patients have proportionally more to lose. Survival was much poorer in other syndromes.

scholarly journals Dopamine Alters Tactile Perception in Parkinson's Disease

2012 ◽  
Vol 39 (1) ◽  
pp. 52-57 ◽  
Author(s):  
Aimee J. Nelson ◽  
Azra Premji ◽  
Navjot Rai ◽  
Tasnuva Hoque ◽  
Mark Tommerdahl ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Temporal Order ◽  
Temporal Order Judgment ◽  
Tactile Perception ◽  
Somatosensory Processing ◽  
Motor Impairments ◽  
Tactile Acuity ◽  
Tactile Stimuli ◽  
The Right

Background:Abnormal somatosensory processing may contribute to motor impairments observed in Parkinson's disease (PD). Dopaminergic medications have been shown to alter somatosensory processing such that tactile perception is improved. In PD, it remains unclear whether the temporal sequencing of tactile stimuli is altered and if dopaminergic medications alter this perception.Methods:Somatosensory tactile perception was investigated using temporal order judgment in patients with Parkinson's disease on and off dopaminergic medications and in aged-matched healthy controls. Measures of temporal order judgment were acquired using computer controlled stimulation to digits 2 and 3 on the right hand and subjects were required to determine which stimuli occurred first. Two experimental tasks were compared, temporal order judgment without and with synchronization whereby digits 2 and 3 were vibrated synchronously in advance of the temporal order judgment sequence of stimuli.Results:Temporal order judgment in PD patients off and on medications were similar to controls. Temporal order judgment preceded by synchronous vibration impaired tactile acuity in controls and in PD off medications to similar degrees, but this perceptual impairment by synchronous vibration was not present in PD patients on medications.Conclusions:These findings suggest that dopamine in PD reduces cortico-cortical connectivity within SI and this leads to changes in tactile sensitivity.

Sign in / Sign up

Export Citation Format

Share Document