Motor neurone

Hemorrhage-induced injury of the corticospinal tract (CST) in the internal capsule (IC) causes severe neurological dysfunction in both human patients and rodent models of intracerebral hemorrhage (ICH). A nuclear receptor Nurr1 (NR4A2) is known to exert anti-inflammatory and neuroprotective effects in several neurological disorders. Previously we showed that Nurr1 ligands prevented CST injury and alleviated neurological deficits after ICH in mice. To prove direct effect of Nurr1 on CST integrity, we examined the effect of Nurr1 overexpression in neurons of the primary motor cortex on pathological consequences of ICH in mice...

Parkinson's Disease is a progressive neurodegenerative disorder characterized by motor symptoms resulting from the loss of nigrostriatal dopaminergic neurons. Kisspeptins (KPs) are a family of neuropeptides that are encoded by the Kiss-1 gene, which exert their physiological effects through interaction with the GPR54 receptor. In the current investigation, we investigated the prospective protective effects of central KP-54 treatments on nigrostriatal dopaminergic neurons and consequent motor performance correlates in 6-hydroxydopamine (6-OHDA)-lesioned rats...

Mutations in SOD1 cause amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by motor neuron (MN) loss. We previously discovered that macrophage migration inhibitory factor (MIF), whose levels are extremely low in spinal MNs, inhibits mutant SOD1 misfolding and toxicity. In this study, we show that a single peripheral injection of adeno-associated virus (AAV) delivering MIF into adult SOD1G37R mice significantly improves their motor function, delays disease progression, and extends survival...

OBJECTIVE: To evaluate the associations between motor unit number index (MUNIX) and disease progression and prognosis in amyotrophic lateral sclerosis (ALS) in a large-scale longitudinal study. METHODS: MUNIX was performed at the patient's first visit, at 3, 6, and 12 months in 4 muscles. MUNIX data from the patients were compared with those from 38 age-matched healthy controls. Clinical data included the revised ALS functional rating scale (ALSFRS-R), the forced vital capacity (FVC), and the survival of the patients...

Pathogenic variants in the UBQLN2 gene cause X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia characterised by ubiquilin 2 aggregates in neurons of the motor cortex, hippocampus, and spinal cord. However, ubiquilin 2 neuropathology is also seen in sporadic and familial amyotrophic lateral sclerosis and/or frontotemporal dementia cases not caused by UBQLN2 pathogenic variants, particularly C9orf72-linked cases. This makes the mechanistic role of mutant ubiquilin 2 protein and the value of ubiquilin 2 pathology for predicting genotype unclear...

Cell transplantation is a promising treatment option for spinal cord injury (SCI). However, there is no consensus on the choice of carrier scaffolds to host the cells. This study aims to evaluate the efficacy of different material scaffold-mediated cell transplantation in treating SCI in rats. According to PRISMA's principle, Embase, PubMed, Web of Science, and Cochrane databases were searched, and relevant literature was referenced. Only original research on cell transplantation plus natural or synthetic scaffolds in SCI rats was included...

INTRODUCTION: Microglia are the main phagocytes in the brain and can induce neuroinflammation. Moreover, they are critical to alpha-synuclein (α-syn) aggregation and propagation. Plasma exosomes derived from patients diagnosed with Parkinson's disease (PD-exo) reportedly evoked α-syn aggregation and inflammation in microglia. In turn, microglia internalized and released exosomal α-syn, enhancing α-syn propagation. However, the specific mechanism through which PD-exo influences α-syn degradation remains unknown...

Selectively focusing on a behaviorally relevant stimulus while ignoring irrelevant stimuli improves perception. Enhanced neuronal response gain is thought to support attention-related improvements in detection and discrimination. However, understanding of the neuronal pathways regulating perceptual sensitivity remains limited. Here, we report that responses of norepinephrine (NE) neurons in the locus coeruleus (LC) of non-human primates to behaviorally relevant sensory stimuli promote visual discrimination in a spatially selective way...

INTRODUCTION: Anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease is a rare autoimmune encephalitis that can mimic progressive supranuclear palsy or corticobasal syndrome. Moreover, anti-IgLON5 disease can present with symptoms characteristic of multiple system atrophy (MSA), such as cerebellar ataxia and autonomic dysfunction. However, the clinical features of anti-IgLON5 disease resembling MSA have not been well established. METHODS: We enrolled 35 patients with suspected MSA for whom anti-IgLON5 antibody tests were requested...

Wireless activation of the enteric nervous system (ENS) in freely moving animals with implantable optogenetic devices offers a unique and exciting opportunity to selectively control gastrointestinal (GI) transit in vivo, including the gut-brain axis. Programmed delivery of light to targeted locations in the GI-tract, however, poses many challenges not encountered within the central nervous system (CNS). We report here the development of a fully implantable, battery-free wireless device specifically designed for optogenetic control of the GI-tract, capable of generating sufficient light over large areas to robustly activate the ENS, potently inducing colonic motility ex vivo and increased propulsion in vivo...

Long-range glutamatergic inputs originating from the cortex and thalamus are indispensable for striatal development, providing the foundation for motor and cognitive functions. Despite their significance, transcriptional regulation governing these inputs remains largely unknown. We investigated the role of a transcription factor encoded by a high-risk autism-associated gene, FOXP1 , in sculpting glutamatergic inputs onto spiny projection neurons (SPNs) within the striatum. We find a neuron subtype-specific role of FOXP1 in strengthening and maturing glutamatergic inputs onto dopamine receptor 2-expressing SPNs (D2 SPNs)...

Neuromodulators have been shown to alter the temporal profile of short-term synaptic plasticity (STP); however, the computational function of this neuromodulation remains unexplored. Here, we propose that the neuromodulation of STP provides a general mechanism to scale neural dynamics and motor outputs in time and space. We trained recurrent neural networks that incorporated STP to produce complex motor trajectories-handwritten digits-with different temporal (speed) and spatial (size) scales. Neuromodulation of STP produced temporal and spatial scaling of the learned dynamics and enhanced temporal or spatial generalization compared to standard training of the synaptic weights in the absence of STP...

BACKGROUND: Spinal muscular atrophy (SMA), a genetic neuromuscular disease caused by lack of survival of motor neuron (SMN) protein, is characterized by muscular atrophy and respiratory and bulbar dysfunction. While swallowing disorders are common, they remain poorly studied. OBJECTIVES: Our study aimed to explore 1) intraoral pressure measurements with the Iowa Oral Performance Instrument system and the reliability of a Swallowing Function Assessment Questionnaire (SFAQ) in healthy controls, and 2) evaluate their use as swallowing function biomarkers and the evolution of swallowing function over time in children with SMA...

Cholecystokinin (CCK) is an essential modulator for neuroplasticity in sensory and emotional domains. Here, we investigated the role of CCK in motor learning using a single pellet reaching task in mice. Mice with a knockout of Cck gene ( Cck-/- ) or blockade of CCK-B receptor (CCKBR) showed defective motor learning ability; the success rate of retrieving reward remained at the baseline level compared to the wildtype mice with significantly increased success rate. We observed no long-term potentiation upon high-frequency stimulation in the motor cortex of Cck-/- mice, indicating a possible association between motor learning deficiency and neuroplasticity in the motor cortex...

Parkinson's disease (PD) is a severe, progressive, neurological disorder. PD is not a single disease, but rather resembles a syndrome. PD includes two types of pathogenesis (i.e., classical PD and new PD). Clinically, PD patients present with a range of motor symptoms including decreased spontaneous movement, bradykinesia, muscle rigidity, changes in speech, and resting tremors. PD patients also often exhibit non-motor symptoms such as fatigue, sleep disorders, and emotional and mental health disturbances. Deep brain stimulation (DBS) performed in clinical neurosurgery has demonstrated considerable efficacy in the treatment of dyskinesia that occurs in PD patients...

The pedunculopontine tegmental nucleus of the brainstem (PPTg) has extensive interconnections and neuronal-behavioural correlates. It is implicated in movement control and sensorimotor integration. We investigated whether single neuron activity in freely moving rats is correlated with components of skilled forelimb movement, and whether individual neurons respond to both motor and sensory events. We found that individual PPTg neurons showed changes in firing rate at different times during the reach. This type of temporally specific modulation is like activity seen elsewhere in voluntary movement control circuits, such as the motor cortex, and suggests that PPTg neural activity is related to different specific events occurring during the reach...

BACKGROUND: Motor Neurone Disease (MND) leads to muscle weakening, affecting movement, speech, and breathing. Home mechanical ventilation, particularly non-invasive ventilation (NIV), is used to alleviate symptoms and support breathing in people living with MND. While home mechanical ventilation can alleviate symptoms and improve survival, it does not slow the progression of MND. This study addresses gaps in understanding end-of-life decision-making in those dependent on home mechanical ventilation, considering the perspectives of patients, family members, and bereaved families...

β-Thalassaemia is one of the most common genetic diseases worldwide. During the past few decades, life expectancy of patients has increased significantly owing to advance in medical treatments. Cognitive impairment, once has been neglected, has gradually become more documented. Cognitive impairment in β-thalassaemia patients is associated with natural history of the disease and socioeconomic factors. Herein, to determined effect of β-thalassaemia intrinsic factors, 22-month-old β-thalassaemia mouse was used as a model to assess cognitive impairment and to investigate any aberrant brain pathology in β-thalassaemia...

Resilience in neuroscience generally refers to an individual's capacity to counteract the adverse effects of a neuropathological condition. While resilience mechanisms in Alzheimer's disease are well-investigated, knowledge regarding its quantification, neurobiological underpinnings, network adaptations, and long-term effects in Parkinson's disease is limited. Our study involved 151 Parkinson's patients from the Parkinson's Progression Marker Initiative Database with available Magnetic Resonance Imaging, Dopamine Transporter Single-Photon Emission Computed Tomography scans, and clinical information...

Amyotrophic Lateral Sclerosis (ALS), like many other neurodegenerative diseases, is highly heritable, but with only a small fraction of cases explained by monogenic disease alleles. To better understand sporadic ALS, we report epigenomic profiles, as measured by ATAC-seq, of motor neuron cultures derived from a diverse group of 380 ALS patients and 80 healthy controls. We find that chromatin accessibility is heavily influenced by sex, the iPSC cell type of origin, ancestry, and the inherent variance arising from sequencing...