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Genes, Brain, and Behavior Sep 2014Mutations in various genes adversely affect locomotion in model organisms, and thus provide valuable clues about the complex processes that control movement. In...
Mutations in various genes adversely affect locomotion in model organisms, and thus provide valuable clues about the complex processes that control movement. In Caenorhabditis elegans, loss-of-function mutations in the Na(+) leak current channel (NALCN) and associated proteins (UNC-79 and UNC-80) cause akinesia and fainting (abrupt freezing of movement during escape from touch). It is not known how defects in the NALCN induce these phenotypes or if they are chronic and irreversible. Here, we report that akinesia and freezing are state-dependent and reversible in NALCN-deficient mutants (nca-1;nca-2, unc-79 and unc-80) when additional cation channels substitute for this protein. Two main measures of locomotion were evaluated: spontaneous movement (traversal of >2 head lengths during a 5 second observation period) and the touch-freeze response (movement greater than three body bends in response to tail touch). Food deprivation for as little as 3 min stimulated spontaneous movement and corrected the touch-freeze response. Conversely, food-deprived animals that moved normally in the absence of bacteria rapidly reverted to uncoordinated movement when re-exposed to food. The effects of food deprivation were mimicked by nicotine, which suggested that acetylcholine mediated the response. Nicotine appeared to act on interneurons or motor neurons rather than directly at the neuromuscular junction because levamisole, which stimulates muscle contraction, did not correct movement. Neural circuits have been proposed to account for the effects of food deprivation and nicotine on spontaneous movement and freezing. The NALCN may play an unrecognized role in human movement disorders characterized by akinesia and freezing gait.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Food Deprivation; Freezing Reaction, Cataleptic; Gait; Ganglionic Stimulants; Interneurons; Levamisole; Locomotion; Motor Neurons; Neuromuscular Junction; Nicotine; Sodium; Sodium Channels
PubMed: 24995777
DOI: 10.1111/gbb.12153 -
Sensors (Basel, Switzerland) Sep 2020In Parkinson's disease (PD), abnormal movements consisting of hypokinetic and hyperkinetic manifestations commonly lead to nocturnal distress and sleep impairment, which... (Review)
Review
In Parkinson's disease (PD), abnormal movements consisting of hypokinetic and hyperkinetic manifestations commonly lead to nocturnal distress and sleep impairment, which significantly impact quality of life. In PD patients, these nocturnal disturbances can reflect disease-related complications (e.g., nocturnal akinesia), primary sleep disorders (e.g., rapid eye movement behaviour disorder), or both, thus requiring different therapeutic approaches. Wearable technologies based on actigraphy and innovative sensors have been proposed as feasible solutions to identify and monitor the various types of abnormal nocturnal movements in PD. This narrative review addresses the topic of abnormal nocturnal movements in PD and discusses how wearable technologies could help identify and assess these disturbances. We first examine the pathophysiology of abnormal nocturnal movements and the main clinical and instrumental tools for the evaluation of these disturbances in PD. We then report and discuss findings from previous studies assessing nocturnal movements in PD using actigraphy and innovative wearable sensors. Finally, we discuss clinical and technical prospects supporting the use of wearable technologies for the evaluation of nocturnal movements.
Topics: Actigraphy; Humans; Hyperkinesis; Hypokinesia; Movement; Parkinson Disease; Quality of Life; Sleep; Sleep Wake Disorders; Wearable Electronic Devices
PubMed: 32927816
DOI: 10.3390/s20185171 -
Parkinsonism & Related Disorders Feb 2023Progressive supranuclear palsy (PSP) is associated with several clinical variants defined based on ocular motor dysfunction, postural instability, akinesia, and...
INTRODUCTION
Progressive supranuclear palsy (PSP) is associated with several clinical variants defined based on ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction, although little is known about how these features progress over time. We aimed to assess the evolution of these core clinical features across variants and assess baseline clinical and neuroimaging predictors of progression.
METHODS
Ninety-three PSP patients were recruited by the Neurodegenerative Research Group, Mayo Clinic, and underwent two visits 1-year apart, with baseline MRI and [F]flortaucipir PET. We compared baseline and annualized rates of clinical change on the PSP Rating Scale (total, ocular motor, gait/midline scores) and Montreal Cognitive Assessment, across PSP-Richardson's, PSP-Cortical and PSP-Subcortical variants and assessed relationships between rates of change and baseline regional imaging.
RESULTS
Ocular motor scores differed across groups at baseline and follow-up, with lowest scores observed in PSP-subcortical, but no differences were observed in rate of change across groups. PSP Rating Scale total and gait/midline scores differed across groups at follow-up and in rates of change, with PSP-subcortical showing the least impairment and slowest progression. Greatest cognitive impairment was observed in PSP-Cortical. Sample size estimates for treatment trials differed across PSP variants. Greater baseline flortaucipir uptake, but not volume, of midbrain and motor cortex correlated with faster rates of clinical decline.
CONCLUSION
The PSP Rating Scale and its subscores might be useful markers for the prognostic stratification of PSP variants. Flortaucipir imaging at baseline may help predict rate of decline.
Topics: Humans; Supranuclear Palsy, Progressive; Neuroimaging; Magnetic Resonance Imaging; Mesencephalon; Eye Movements
PubMed: 36682219
DOI: 10.1016/j.parkreldis.2023.105290 -
Trends in Neurosciences Nov 2011Multiple system atrophy (MSA) is a neurodegenerative disease involving motor abnormalities that include akinesia, rigidity and postural instability. While improved... (Review)
Review
Multiple system atrophy (MSA) is a neurodegenerative disease involving motor abnormalities that include akinesia, rigidity and postural instability. While improved diagnostic criteria have aided the accurate diagnosis of MSA, our understanding of the neuropathological aspects underlying MSA was bolstered by the identification of α-synuclein (α-syn) as the primary constituent of the abnormal protein aggregates observed in the brains of MSA patients. The generation of transgenic animal models of MSA coupled with an increasing understanding of the biochemical structure and function of α-syn has highlighted a number of key pathological pathways thought to underlie the neurodegeneration observed in MSA. This review summarizes key findings in the field, discusses current areas of debate, and describes current experimental approaches towards disease-modifying therapies.
Topics: Animals; Animals, Genetically Modified; Brain; Disease Models, Animal; Humans; Multiple System Atrophy; Oligodendroglia; alpha-Synuclein
PubMed: 21962754
DOI: 10.1016/j.tins.2011.08.003 -
Journal of Anatomy May 2000Models of basal ganglia function are described which encapsulate the principal pathophysiological mechanisms underlying parkinsonian akinesia on the one hand and... (Review)
Review
Models of basal ganglia function are described which encapsulate the principal pathophysiological mechanisms underlying parkinsonian akinesia on the one hand and abnormal involuntary movement disorders (dyskinesias) on the other. In Parkinson's disease, degeneration of the nigrostriatal dopamine system leads to overactivity of the 'indirect' striatopallidal projection to the lateral (external) segment of the globus pallidus. This causes inhibition of lateral pallidal neurons, which in turn project to the subthalamic nucleus. Disinhibition of the subthalamic nucleus leads to abnormal subthalamic overactivity and, as a consequence, overactivity of medial (internal) pallidal output neurons. Dyskinesias, such as are observed in Huntington's disease, levodopa-induced dyskinesia and ballism, share mechanistic features in common and are associated with decreased neuronal activity in both the subthalamic nucleus and the medial globus pallidus.
Topics: Animals; Basal Ganglia; Dyskinesias; Humans; Movement Disorders; Neural Pathways; Neurotransmitter Agents; Parkinson Disease
PubMed: 10923984
DOI: 10.1046/j.1469-7580.2000.19640519.x -
Annals of Indian Academy of Neurology 2022Levodopa (L-dopa) is the gold standard in the management of Parkinson's disease (PD). It dates back to 1500 to 1000 BC when it was used in the Indian Ayurvedic and...
Levodopa (L-dopa) is the gold standard in the management of Parkinson's disease (PD). It dates back to 1500 to 1000 BC when it was used in the Indian Ayurvedic and Chinese system of medicine. Certain beans such as and contain L-dopa. The plant (Mp) or velvet bean, cultivated in Eastern India and Southern China, contains L-dopa at a concentration of 5% and was used for the management of PD. Later, workers have documented the neuroprotective, neurorestorative, and immunomodulatory properties of Mp. Double-blind studies conducted in the Western world have proved the efficacy of Mp and reported some toxic side effects as well. In the Western world, the credit for isolating L-dopa from the seeds of or goes to Markus Guggenheim, a biochemist from Sweden in 1913. However, it has been used with success ever since Arvid Carlsson established the reversibility of reserpine-induced akinesia in rabbits in the late 1950s with the use of intravenous dopamine, and Oleh Hornykiewicz demonstrated its deficiency in the striatum in 1960-1961. George Cotzias used it in patients in a low and slow incremental fashion in 1967, and Melvin Yahr and his colleagues performed double-blind study on in-patients with success in 1969. Complications with its long-term use, particularly the on-off phenomenon, and dyskinesias appeared soon, and measures have been undertaken to reduce their incidence. Researches on alternative modes of delivery are carried out in various centers, and others are under investigation in the laboratories.
PubMed: 35342258
DOI: 10.4103/aian.aian_474_21 -
The Application of Clinical Genetics 2018Pena-Shokeir syndrome (PSS) type 1, also known as fetal akinesia deformation sequence, is a rare genetic syndrome that almost always results in intrauterine or early... (Review)
Review
Pena-Shokeir syndrome (PSS) type 1, also known as fetal akinesia deformation sequence, is a rare genetic syndrome that almost always results in intrauterine or early neonatal death. It is characterized by markedly decreased fetal movements, intrauterine growth restriction, joint contractures, short umbilical cord, and features of pulmonary hypoplasia. Antenatal diagnosis can be difficult. Ultrasound features are varied and may overlap with those of Trisomy 18. The poor prognosis of PSS is due to pulmonary hypoplasia, which is an important feature that distinguishes PSS from arthrogryposis multiplex congenital without pulmonary hypoplasia, which has a better prognosis. If diagnosed in the antenatal period, a late termination of pregnancy can be considered following ethical discussion (if the law allows). In most cases, a diagnosis is only made in the neonatal period. Parents of a baby affected with PSS require detailed counseling that includes information on the imprecise recurrence risks and a plan for subsequent pregnancies.
PubMed: 30498368
DOI: 10.2147/TACG.S154643 -
Saudi Pharmaceutical Journal : SPJ :... Dec 2022Parkinson's disease (PD) is the gradual and selective degradation of dopamine-releasing neurons in substantia nigra pars compacta (SNpc) and results in postural...
Parkinson's disease (PD) is the gradual and selective degradation of dopamine-releasing neurons in substantia nigra pars compacta (SNpc) and results in postural instability, stiffness, bradykinesia, and resting tremor. The goal of this research was to see how hibiscetin action on PD in rotenone-treated rats. Rats were administered orally with hibiscetin (10 mg/kg) after 1 h rotenone (0.5 mg/kg, s.c.). This therapy regimen was followed on a daily basis for 28 days. Rats were tested for catalepsy and akinesia on day 29 after the last dosage of rotenone. Biochemical parameters were performed to measure reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), nitrite, neuroinflammatory cytokines, and neurotransmitter and their metabolite levels such as dopamine (DA), norepinephrine (NE), serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA). Rotenone-induced akinesia and catatonia in rats decreased endogenous antioxidant (GSH, CAT, and SOD) levels, increased MDA and nitrite levels, and changed neurotransmitter and metabolite levels. Hibiscetin effectively reduced rotenone-induced akinesia and catatonia, improved endogenous antioxidant (GSH, CAT and SOD) levels, and reduced oxidative and nitrative stress in the treated rats. Moreover, hibiscetin restored altered neurotransmitters and their metabolites to normal levels in rotenone-treated rats. The study results showed that hibiscetin has anti-Parkinson's activity against rotenone-induced PD in rats.
PubMed: 36601498
DOI: 10.1016/j.jsps.2022.09.016 -
Genes Mar 2022Parkinson's disease (PD) is a disorder characterized by a triad of motor symptoms (akinesia, rigidity, resting tremor) related to loss of dopaminergic neurons mainly in... (Review)
Review
Parkinson's disease (PD) is a disorder characterized by a triad of motor symptoms (akinesia, rigidity, resting tremor) related to loss of dopaminergic neurons mainly in the . Diagnosis is often made after a substantial loss of neurons has already occurred, and while dopamine replacement therapies improve symptoms, they do not modify the course of the disease. Although some biological mechanisms involved in the disease have been identified, such as oxidative stress and accumulation of misfolded proteins, they do not explain entirely PD pathophysiology, and a need for a better understanding remains. Neurodegenerative diseases, including PD, appear to be the result of complex interactions between genetic and environmental factors. The latter can alter gene expression by causing epigenetic changes, such as DNA methylation, post-translational modification of histones and non-coding RNAs. Regulation of genes responsible for monogenic forms of PD may be involved in sporadic PD. This review will focus on the epigenetic mechanisms regulating their expression, since these are the genes for which we currently have the most information available. Despite technical challenges, epigenetic epidemiology offers new insights on revealing altered biological pathways and identifying predictive biomarkers for the onset and progression of PD.
Topics: Dopamine; Dopaminergic Neurons; Epigenesis, Genetic; Epigenomics; Humans; Parkinson Disease
PubMed: 35328033
DOI: 10.3390/genes13030479 -
Neurotherapeutics : the Journal of the... Oct 2023Traumatic brain injury (TBI), a neurovascular injury caused by external force, is a common diagnosis among veterans and those experiencing homelessness (HL). There is a... (Review)
Review
Traumatic brain injury (TBI), a neurovascular injury caused by external force, is a common diagnosis among veterans and those experiencing homelessness (HL). There is a significant overlap in the veteran and homeless population, possibly accounting for the two to seven times greater incidence of TBI among those experiencing HL than the general population. Despite these statistics, individuals experiencing HL are often underdiagnosed and ineffectively treated for TBI. We introduced a novel model of HL. Over 5 weeks, adult Sprague-Dawley rats were randomly assigned to one of the following conditions: TBI only, HL only, TBI + HL, or control (n = 9 per group). To emulate HL, animals (2 animals per cage) were exposed to soiled beddings for 5 weeks. Subsequently, animals were introduced to TBI by using the moderate controlled cortical impact model, then underwent 4 consecutive days of behavioral testing (beam walk (BW), elevated body swing test (EBST), forelimb akinesia (FA), paw grasp (PG), Rotorod, and elevated T-maze). Nissl staining was performed to determine the peri-impact cell survival and the integrity of corpus callosum area. Motor function was significantly impaired by TBI, regardless of housing (beam walk or BW 85.0%, forelimb akinesia or FA 104.7%, and paw grasp or PG 100% greater deficit compared to control). Deficits were worsened by HL in TBI rats (BW 93.3%, FA 40.5%, and PG 50% greater deficit). Two-way ANOVA revealed BW (F(4, 160) = 31.69, p < 0.0001), FA (F(4, 160) = 13.71, p < 0.0001), PG (F(4, 160) = 3.873, p = 0.005), Rotorod (F(4, 160), p = 1.116), and EBST (F(4, 160) = 6.929, p < 0.0001) showed significant differences between groups. The Rotorod and EBST tests showed TBI-induced functional deficits when analyzed by day, but these deficits were not exacerbated by HL. TBI only and TBI + HL rats exhibited typical cortical impact damage (F(3,95) = 51.75, p < 0.0001) and peri-impact cell loss compared to control group (F(3,238) = 47.34, p < 0.0001). Most notably, TBI + HL rats showed significant alterations in WM area measured via the corpus callosum (F(3, 95) = 3.764, p = 0.0133). Worsened behavioral outcomes displayed by TBI + HL rats compared to TBI alone suggest HL contributes to TBI functional deficits. While an intact white matter, such as the corpus callosum, may lessen the consequent functional deficits associated with TBI by enhancing hemispheric communications, there are likely alternative cellular and molecular pathways mitigating TBI-associated inflammatory or oxidative stress responses. Here, we showed that the environmental condition of the patient, i.e., HL, participates in white matter integrity and behavioral outcomes, suggesting its key role in the disease diagnosis to aptly treat TBI patients.
Topics: Humans; Adult; Rats; Animals; Rats, Sprague-Dawley; Brain Injuries, Traumatic; White Matter; Ill-Housed Persons; Comorbidity
PubMed: 37639189
DOI: 10.1007/s13311-023-01419-8