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Journal of Parkinson's Disease 2024Previous studies have demonstrated the importance of the locus coeruleus (LC) in sleep-wake regulation. Both essential tremor (ET) and Parkinson's disease (PD) share...
BACKGROUND
Previous studies have demonstrated the importance of the locus coeruleus (LC) in sleep-wake regulation. Both essential tremor (ET) and Parkinson's disease (PD) share common sleep disorders, such as poor quality of sleep (QoS). LC pathology is a feature of both diseases. A question arises regarding the contribution of LC degeneration to the occurrence of poor QoS.
OBJECTIVE
To evaluate the association between LC impairment and sleep disorders in ET and PD patients.
METHODS
A total of 83 patients with ET, 124 with PD, and 83 healthy individuals were recruited and divided into ET/PD with/without poor QoS (Sle/NorET and Sle/NorPD) subgroups according to individual Pittsburgh Sleep Quality Index (PSQI) score. Neuromelanin-sensitive magnetic resonance imaging (NM-MRI) and free-water imaging derived from diffusion MRI were performed. Subsequently, we evaluated the association between contrast-to-noise ratio of LC (CNRLC) and free-water value of LC (FWLC) with PSQI scores in ET and PD groups.
RESULTS
CNRLC was significantly lower in ET (p = 0.047) and PD (p = 0.018) than in healthy individuals, whereas no significant difference was found in FWLC among the groups. No significant differences were observed in CNR/FWLC between patients with/without sleep disorders after multiple comparison correction. No correlation was identified between CNR/FWLC and PSQI in ET and PD patients.
CONCLUSIONS
LC degeneration was observed in both ET and PD patients, implicating its involvement in the pathophysiology of both diseases. Additionally, no significant association was observed between LC integrity and PSQI, suggesting that LC impairment might not directly relate to overall QoS.
Topics: Humans; Essential Tremor; Locus Coeruleus; Female; Male; Parkinson Disease; Aged; Middle Aged; Sleep Wake Disorders; Magnetic Resonance Imaging; Nerve Degeneration; Sleep Quality; Melanins
PubMed: 38728202
DOI: 10.3233/JPD-240001 -
Scientific Reports May 2024Homeostatic plasticity, the ability of neurons to maintain their averaged activity constant around a set point value, is thought to account for the central hyperactivity...
Homeostatic plasticity, the ability of neurons to maintain their averaged activity constant around a set point value, is thought to account for the central hyperactivity after hearing loss. Here, we investigated the putative role of GABAergic neurotransmission in this mechanism after a noise-induced hearing loss larger than 50 dB in high frequencies in guinea pigs. The effect of GABAergic inhibition is linked to the normal functioning of K + -Cl- co-transporter isoform 2 (KCC2) which maintains a low intracellular concentration of chloride. The expression of membrane KCC2 were investigated before and after noise trauma in the ventral and dorsal cochlear nucleus (VCN and DCN, respectively) and in the inferior colliculus (IC). Moreover, the effect of gabazine (GBZ), a GABA antagonist, was also studied on the neural activity in IC. We show that KCC2 is downregulated in VCN, DCN and IC 3 days after noise trauma, and in DCN and IC 30 days after the trauma. As expected, GBZ application in the IC of control animals resulted in an increase of spontaneous and stimulus-evoked activity. In the noise exposed animals, on the other hand, GBZ application decreased the stimulus-evoked activity in IC neurons. The functional implications of these central changes are discussed.
Topics: Animals; Symporters; Guinea Pigs; K Cl- Cotransporters; Hearing Loss, Noise-Induced; gamma-Aminobutyric Acid; Male; Cochlear Nucleus; Pyridazines; Neurons
PubMed: 38724641
DOI: 10.1038/s41598-024-60858-1 -
Experimental Brain Research Jun 2024Cerebellar strokes induce coordination disorders that can affect activities of daily living. Evidence-based neurorehabilitation programs are founded on motor learning...
Cerebellar strokes induce coordination disorders that can affect activities of daily living. Evidence-based neurorehabilitation programs are founded on motor learning principles. The cerebellum is a key neural structure in motor learning. It is unknown whether and how well chronic cerebellar stroke individuals (CCSIs) can learn to coordinate their upper limbs through bimanual motor skill learning. The aim was to determine whether CCSIs could achieve bimanual skill learning through a serious game with the REAplan robot and to compare CCSIs with healthy individuals (HIs). Over three consecutive days, sixteen CCSIs and eighteen HIs were trained on an asymmetric bimanual coordination task ("CIRCUIT" game) with the REAplan robot, allowing quantification of speed, accuracy and coordination. The primary outcomes were the bimanual speed/accuracy trade-off (BiSAT) and bimanual coordination factor (BiCo). They were also evaluated on a bimanual REACHING task on Days 1 and 3. Correlation analyses between the robotic outcomes and clinical scale scores were computed. Throughout the sessions, BiSAT and BiCo improved during the CIRCUIT task in both HIs and CCSIs. On Day 3, HIs and CCSIs showed generalization of BiSAT, BiCo and transferred to the REACHING task. There was no significant between-group difference in progression. Four CCSIs and two HIs were categorized as "poor learners" according to BiSAT and/or BiCo. Increasing age correlated with reduced BiSAT but not BiCo progression. Over three days of training, HIs and CCSIs improved, retained, generalized and transferred a coordinated bimanual skill. There was no between-group difference, suggesting plastic compensation in CCSIs. Clinical trial NCT04642599 approved the 24th of November 2020.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Cerebellar Diseases; Cerebellum; Chronic Disease; Learning; Motor Skills; Psychomotor Performance; Robotics; Stroke; Stroke Rehabilitation; Prospective Studies; Adolescent; Aged, 80 and over
PubMed: 38722346
DOI: 10.1007/s00221-024-06830-x -
Environmental Pollution (Barking, Essex... Jul 2024Lead (Pb) is a heavy metal that has been recognized as a neurotoxin, meaning it can cause harmful effects on the nervous system. However, the neurotoxicology of Pb to...
Lead induced cerebellar toxicology of developmental Japanese quail (Coturnix japonica) via oxidative stress-based Nrf2/Keap1 pathway inhibition and glutathione-mediated apoptosis signaling activation.
Lead (Pb) is a heavy metal that has been recognized as a neurotoxin, meaning it can cause harmful effects on the nervous system. However, the neurotoxicology of Pb to birds still needs further study. In this study, we examined the neurotoxic effects of Pb exposure on avian cerebellum by using an animal model-Japanese quail (Coturnix japonica). The one-week old male chicks were exposed to 50, 200 and 500 mg/kg Pb of environmental relevance in the feed for five weeks. The results showed Pb caused cerebellar microstructural damages charactered by deformation of neuroglia cells, granule cells and Purkinje cells with Nissl body changes. Moreover, cerebellar neurotransmission was disturbed by Pb with increasing acetylcholine (ACh) and decreasing acetylcholinesterase (AChE), dopamine (DA), γ-Aminobutyric Acid (GABA) and Na/K ATPase. Meanwhile, cerebellar oxidative stress was caused by Pb exposure represented by increasing reactive oxygen species (ROS) and malondialdehyde (MDA) as well as decreasing catalase (CAT), glutathione peroxidase (GPX), glutathione (GSH) and superoxide dismutase (SOD). Moreover, RNA-Seq analysis showed that molecular signaling pathways in the cerebellum were disrupted by Pb exposure. In particular, the disruption of nuclear factor erythroid-2-related factor 2 (Nfr2)/kelch-like ECH-associated protein 1 (Keap1) pathway and glutathione metabolism pathway indicated increasing cell apoptosis and functional disorder in the cerebellum. The present study revealed that Pb induced cerebellar toxicology through structural injury, oxidative stress, neurotransmission interference and abnormal apoptosis.
Topics: Animals; Lead; Coturnix; Oxidative Stress; Apoptosis; Cerebellum; NF-E2-Related Factor 2; Male; Kelch-Like ECH-Associated Protein 1; Glutathione; Signal Transduction; Environmental Pollutants; Reactive Oxygen Species
PubMed: 38718965
DOI: 10.1016/j.envpol.2024.124114 -
Annals of Clinical and Translational... Jun 2024Mitochondrial impairments have been implicated in the pathogenesis of Fragile X-associated tremor/ataxia syndrome (FXTAS) based on analysis of mitochondria in peripheral...
OBJECTIVE
Mitochondrial impairments have been implicated in the pathogenesis of Fragile X-associated tremor/ataxia syndrome (FXTAS) based on analysis of mitochondria in peripheral tissues and cultured cells. We sought to assess whether mitochondrial abnormalities present in postmortem brain tissues of patients with FXTAS are also present in plasma neuron-derived extracellular vesicles (NDEVs) from living carriers of fragile X messenger ribonucleoprotein1 (FMR1) gene premutations at an early asymptomatic stage of the disease continuum.
METHODS
We utilized postmortem frozen cerebellar and frontal cortex samples from a cohort of eight patients with FXTAS and nine controls and measured the quantity and activity of the mitochondrial proteins complex IV and complex V. In addition, we evaluated the same measures in isolated plasma NDEVs by selective immunoaffinity capture targeting L1CAM from a separate cohort of eight FMR1 premutation carriers and four age-matched controls.
RESULTS
Lower complex IV and V quantity and activity were observed in the cerebellum of FXTAS patients compared to controls, without any differences in total mitochondrial content. No patient-control differences were observed in the frontal cortex. In NDEVs, FMR1 premutation carriers compared to controls had lower activity of Complex IV and Complex V, but higher Complex V quantity.
INTERPRETATION
Quantitative and functional abnormalities in mitochondrial electron transport chain complexes IV and V seen in the cerebellum of patients with FXTAS are also manifest in plasma NDEVs of FMR1 premutation carriers. Plasma NDEVs may provide further insights into mitochondrial pathologies in this syndrome and could potentially lead to the development of biomarkers for predicting symptomatic FXTAS among premutation carriers and disease monitoring.
Topics: Humans; Fragile X Syndrome; Tremor; Extracellular Vesicles; Ataxia; Male; Aged; Female; Fragile X Mental Retardation Protein; Middle Aged; Mitochondria; Cerebellum; Aged, 80 and over; Brain; Frontal Lobe
PubMed: 38717724
DOI: 10.1002/acn3.52040 -
Current Biology : CB May 2024The posterior cerebellum is emerging as a key structure for social cognition. A new study causally demonstrates its early involvement during emotion perception and...
The posterior cerebellum is emerging as a key structure for social cognition. A new study causally demonstrates its early involvement during emotion perception and functional connectivity with the posterior superior temporal sulcus, a cortical hub of the social brain.
Topics: Humans; Cerebellum; Social Perception; Emotions; Social Cognition; Temporal Lobe
PubMed: 38714159
DOI: 10.1016/j.cub.2024.03.028 -
Developmental Cognitive Neuroscience Jun 2024The human cerebellum emerges as a posterior brain structure integrating neural networks for sensorimotor, cognitive, and emotional processing across the lifespan....
INTRODUCTION
The human cerebellum emerges as a posterior brain structure integrating neural networks for sensorimotor, cognitive, and emotional processing across the lifespan. Developmental studies of the cerebellar anatomy and function are scant. We examine age-dependent MRI morphometry of the anterior cerebellar vermis, lobules I-V and posterior neocortical lobules VI-VII and their relationship to sensorimotor and cognitive functions.
METHODS
Typically developing children (TDC; n=38; age 9-15) and healthy adults (HAC; n=31; 18-40) participated in high-resolution MRI. Rigorous anatomically informed morphometry of the vermis lobules I-V and VI-VII and total brain volume (TBV) employed manual segmentation computer-assisted FreeSurfer Image Analysis Program [http://surfer.nmr.mgh.harvard.edu]. The neuropsychological scores (WASI-II) were normalized and related to volumes of anterior, posterior vermis, and TBV.
RESULTS
TBVs were age independent. Volumes of I-V and VI-VII were significantly reduced in TDC. The ratio of VI-VII to I-V (∼60%) was stable across age-groups; I-V correlated with visual-spatial-motor skills; VI-VII with verbal, visual-abstract and FSIQ.
CONCLUSIONS
In TDC neither anterior I-V nor posterior VI-VII vermis attained adult volumes. The "inverted U" developmental trajectory of gray matter peaking in adolescence does not explain this finding. The hypothesis of protracted development of oligodendrocyte/myelination is suggested as a contributor to TDC's lower cerebellar vermis volumes.
Topics: Humans; Adolescent; Child; Female; Male; Magnetic Resonance Imaging; Cognition; Adult; Young Adult; Cerebellar Vermis; Cerebellum
PubMed: 38713999
DOI: 10.1016/j.dcn.2024.101385 -
Alzheimer's Research & Therapy May 2024The locus coeruleus (LC) and the nucleus basalis of Meynert (NBM) are altered in early stages of Alzheimer's disease (AD). Little is known about LC and NBM alteration in...
BACKGROUND
The locus coeruleus (LC) and the nucleus basalis of Meynert (NBM) are altered in early stages of Alzheimer's disease (AD). Little is known about LC and NBM alteration in limbic-predominant age-related TDP-43 encephalopathy (LATE) and frontotemporal dementia (FTD). The aim of the present study is to investigate in vivo LC and NBM integrity in patients with suspected-LATE, early-amnestic AD and FTD in comparison with controls.
METHODS
Seventy-two participants (23 early amnestic-AD patients, 17 suspected-LATE, 17 FTD patients, defined by a clinical-biological diagnosis reinforced by amyloid and tau PET imaging, and 15 controls) underwent neuropsychological assessment and 3T brain MRI. We analyzed the locus coeruleus signal intensity (LC-I) and the NBM volume as well as their relation with cognition and with medial temporal/cortical atrophy.
RESULTS
We found significantly lower LC-I and NBM volume in amnestic-AD and suspected-LATE in comparison with controls. In FTD, we also observed lower NBM volume but a slightly less marked alteration of the LC-I, independently of the temporal or frontal phenotype. NBM volume was correlated with the global cognitive efficiency in AD patients. Strong correlations were found between NBM volume and that of medial temporal structures, particularly the amygdala in both AD and FTD patients.
CONCLUSIONS
The alteration of LC and NBM in amnestic-AD, presumed-LATE and FTD suggests a common vulnerability of these structures to different proteinopathies. Targeting the noradrenergic and cholinergic systems could be effective therapeutic strategies in LATE and FTD.
Topics: Humans; Frontotemporal Dementia; Male; Locus Coeruleus; Alzheimer Disease; Female; Aged; Magnetic Resonance Imaging; Basal Nucleus of Meynert; Middle Aged; Neuropsychological Tests; Amnesia; Positron-Emission Tomography
PubMed: 38702802
DOI: 10.1186/s13195-024-01466-z -
Communications Biology May 2024An organism's ability to accurately anticipate the sensations caused by its own actions is crucial for a wide range of behavioral, perceptual, and cognitive functions....
An organism's ability to accurately anticipate the sensations caused by its own actions is crucial for a wide range of behavioral, perceptual, and cognitive functions. Notably, the sensorimotor expectations produced when touching one's own body attenuate such sensations, making them feel weaker and less ticklish and rendering them easily distinguishable from potentially harmful touches of external origin. How the brain learns and keeps these action-related sensory expectations updated is unclear. Here we employ psychophysics and functional magnetic resonance imaging to pinpoint the behavioral and neural substrates of dynamic recalibration of expected temporal delays in self-touch. Our psychophysical results reveal that self-touches are less attenuated after systematic exposure to delayed self-generated touches, while responses in the contralateral somatosensory cortex that normally distinguish between delayed and nondelayed self-generated touches become indistinguishable. During the exposure, the ipsilateral anterior cerebellum shows increased activity, supporting its proposed role in recalibrating sensorimotor predictions. Moreover, responses in the cingulate areas gradually increase, suggesting that as delay adaptation progresses, the nondelayed self-touches trigger activity related to cognitive conflict. Together, our results show that sensorimotor predictions in the simplest act of touching one's own body are upheld by a sophisticated and flexible neural mechanism that maintains them accurate in time.
Topics: Humans; Somatosensory Cortex; Male; Magnetic Resonance Imaging; Cerebellum; Female; Adult; Young Adult; Touch Perception; Touch
PubMed: 38702520
DOI: 10.1038/s42003-024-06188-4 -
BioEssays : News and Reviews in... Jun 2024Despite its uniform appearance, the cerebellar cortex is highly heterogeneous in terms of structure, genetics and physiology. Purkinje cells (PCs), the principal and... (Review)
Review
Despite its uniform appearance, the cerebellar cortex is highly heterogeneous in terms of structure, genetics and physiology. Purkinje cells (PCs), the principal and sole output neurons of the cerebellar cortex, can be categorized into multiple populations that differentially express molecular markers and display distinctive physiological features. Such features include action potential rate, but also their propensity for synaptic and intrinsic plasticity. However, the precise molecular and genetic factors that correlate with the differential physiological properties of PCs remain elusive. In this article, we provide a detailed overview of the cellular mechanisms that regulate PC activity and plasticity. We further perform a pathway analysis to highlight how molecular characteristics of specific PC populations may influence their physiology and plasticity mechanisms.
Topics: Purkinje Cells; Animals; Neuronal Plasticity; Humans; Action Potentials; Synapses; Cerebellar Cortex
PubMed: 38697917
DOI: 10.1002/bies.202400008