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Nature Communications May 2024About half of the neurons in the parabrachial nucleus (PB) that are activated by CO are located in the external lateral (el) subnucleus, express calcitonin gene-related...
About half of the neurons in the parabrachial nucleus (PB) that are activated by CO are located in the external lateral (el) subnucleus, express calcitonin gene-related peptide (CGRP), and cause forebrain arousal. We report here, in male mice, that most of the remaining CO-responsive neurons in the adjacent central lateral (PBcl) and Kölliker-Fuse (KF) PB subnuclei express the transcription factor FoxP2 and many of these neurons project to respiratory sites in the medulla. PBcl neurons show increased intracellular calcium during wakefulness and REM sleep and in response to elevated CO during NREM sleep. Photo-activation of the PBcl neurons increases respiration, whereas either photo-inhibition of PBcl or genetic deletion of PB/KF neurons reduces the respiratory response to CO stimulation without preventing awakening. Thus, augmenting the PBcl/KF response to CO in patients with sleep apnea in combination with inhibition of the PBel neurons may avoid hypoventilation and minimize EEG arousals.
Topics: Animals; Hypercapnia; Neurons; Male; Parabrachial Nucleus; Forkhead Transcription Factors; Mice; Carbon Dioxide; Wakefulness; Respiration; Mice, Inbred C57BL; Calcitonin Gene-Related Peptide; Sleep, REM; Repressor Proteins
PubMed: 38796568
DOI: 10.1038/s41467-024-48773-5 -
Cellular and Molecular Life Sciences :... May 2024Vanishing white matter (VWM) is a leukodystrophy caused by biallelic pathogenic variants in eukaryotic translation initiation factor 2B. To date, it remains unclear...
Vanishing white matter (VWM) is a leukodystrophy caused by biallelic pathogenic variants in eukaryotic translation initiation factor 2B. To date, it remains unclear which factors contribute to VWM pathogenesis. Here, we investigated the basis of VWM pathogenesis using the 2b5 mouse model. We first mapped the temporal proteome in the cerebellum, corpus callosum, cortex, and brainstem of 2b5 and wild-type (WT) mice. Protein changes observed in 2b5 mice were then cross-referenced with published proteomic datasets from VWM patient brain tissue to define alterations relevant to the human disease. By comparing 2b5 mice with their region- and age-matched WT counterparts, we showed that the proteome in the cerebellum and cortex of 2b5 mice was already dysregulated prior to pathology development, whereas proteome changes in the corpus callosum only occurred after pathology onset. Remarkably, protein changes in the brainstem were transient, indicating that a compensatory mechanism might occur in this region. Importantly, 2b5 mouse brain proteome changes reflect features well-known in VWM. Comparison of the 2b5 mouse and VWM patient brain proteomes revealed shared changes. These could represent changes that contribute to the disease or even drive its progression in patients. Taken together, we show that the 2b5 mouse brain proteome is affected in a region- and time-dependent manner. We found that the 2b5 mouse model partly replicates the human disease at the protein level, providing a resource to study aspects of VWM pathogenesis by highlighting alterations from early to late disease stages, and those that possibly drive disease progression.
Topics: Animals; Proteomics; Mice; Humans; Proteome; Leukoencephalopathies; Disease Models, Animal; White Matter; Corpus Callosum; Eukaryotic Initiation Factor-2B; Brain; Mice, Inbred C57BL; Cerebellum
PubMed: 38789799
DOI: 10.1007/s00018-024-05258-4 -
Experimental Neurology Aug 2024Cerebral Palsy (CP) is the main motor disorder in childhood resulting from damage to the developing brain. Treatment perspectives are required to reverse the primary...
Neonatal resveratrol treatment in cerebral palsy model recovers neurodevelopment impairments by restoring the skeletal muscle morphology and decreases microglial activation in the cerebellum.
Cerebral Palsy (CP) is the main motor disorder in childhood resulting from damage to the developing brain. Treatment perspectives are required to reverse the primary damage caused by the early insult and consequently to recover motor skills. Resveratrol has been shown to act as neuroprotection with benefits to skeletal muscle. This study aimed to investigate the effects of neonatal resveratrol treatment on neurodevelopment, skeletal muscle morphology, and cerebellar damage in CP model. Wistar rat pups were allocated to four experimental groups (n = 15/group) according CP model and treatment: Control+Saline (CS), Control+Resveratrol (CR), CP + Saline (CPS), and CP + Resveratrol (CPR). CP model associated anoxia and sensorimotor restriction. CP group showed delay in the disappearance of the palmar grasp reflex (p < 0.0001) and delay in the appearance of reflexes of negative geotaxis (p = 0.01), and free-fall righting (p < 0.0001), reduced locomotor activity and motor coordination (p < 0.05) than CS group. These motor skills impairments were associated with a reduction in muscle weight (p < 0.001) and area and perimeter of soleus end extensor digitorum longus muscle fibers (p < 0.0001), changes in muscle fibers typing pattern (p < 0.05), and the cerebellum showed signs of neuroinflammation due to elevated density and percentage of activated microglia in the CPS group compared to CS group (p < 0.05). CP animals treated with resveratrol showed anticipation of the appearance of negative geotaxis and free-fall righting reflexes (p < 0.01), increased locomotor activity (p < 0.05), recovery muscle fiber types pattern (p < 0.05), and reversal of the increase in density and the percentage of activated microglia in the cerebellum (p < 0.01). Thus, we conclude that neonatal treatment with resveratrol can contribute to the recovery of the delay neurodevelopment resulting from experimental CP due to its action in restoring the skeletal muscle morphology and reducing neuroinflammation from cerebellum.
Topics: Resveratrol; Animals; Rats, Wistar; Cerebellum; Rats; Animals, Newborn; Microglia; Cerebral Palsy; Muscle, Skeletal; Disease Models, Animal; Stilbenes; Male; Recovery of Function; Female
PubMed: 38789024
DOI: 10.1016/j.expneurol.2024.114835 -
Medicine May 2024Subacute combined degeneration of the spinal cord is a degenerative disease of the central and peripheral nervous systems caused by vitamin B12 deficiency, mainly...
RATIONALE
Subacute combined degeneration of the spinal cord is a degenerative disease of the central and peripheral nervous systems caused by vitamin B12 deficiency, mainly involving the spinal cord posterior, lateral, and peripheral nerves, but rarely involving the cerebellum.
PATIENT CONCERNS
A 41-year-old woman presented with a 2-year history of walking unsteadily. Her hematologic examination revealed megaloblastic anemia and vitamin B12 deficiency. Electromyography showed multiple peripheral nerve damage (sensory fibers and motor fibers were involved). Imaging examination showed long T2 signal in the cervical, thoracic and lumbar spinal cord and cerebellum. Gastroscopy revealed autoimmune gastritis.
DIAGNOSES
Subacute combined degeneration of the spinal cord.
INTERVENTIONS
By supplementing with vitamin B12.
OUTCOMES
The patient's symptoms of limb weakness, diet, and consciousness were improved, and the muscle strength of both lower limbs recovered to grade IV.
LESSONS
The symptomatic people should seek medical treatment in time to avoid further deterioration of the disease. When esophagogastroduodenoscopy is performed as part of routine physical examination in asymptomatic people, it should be checked for the presence of autoimmune gastritis. Early diagnosis can prevent irreversible neuropathy.
Topics: Humans; Female; Adult; Subacute Combined Degeneration; Vitamin B 12 Deficiency; Gastritis; Vitamin B 12; Cerebellum; Magnetic Resonance Imaging
PubMed: 38788012
DOI: 10.1097/MD.0000000000037605 -
No Shinkei Geka. Neurological Surgery May 2024The basilar artery(BA)is formed by the fusion of two longitudinal arteries, and incomplete development may lead to BA fenestration. The BA provides many short... (Review)
Review
The basilar artery(BA)is formed by the fusion of two longitudinal arteries, and incomplete development may lead to BA fenestration. The BA provides many short perforating arteries and long lateral pontine arteries to the brain stem. The anterior inferior cerebellar artery(AICA)usually branches from the proximal third of the BA and primarily perfuses the ventral, inferior and lateral aspect of the cerebellum and inner ear organ. However, there are many variations to the AICA that depend on the degree of posterior inferior cerebellar artery development. The superior cerebellar artery(SCA)branches into not only to the rostral, ventral aspect of the cerebellar hemisphere, but also to the deeper cerebellar nucleus and brain stem. Duplications within this vessel are frequently identified, but it is not missing.
Topics: Humans; Basilar Artery; Cerebellum
PubMed: 38783494
DOI: 10.11477/mf.1436204944 -
No Shinkei Geka. Neurological Surgery May 2024The angioarchitecture of the hindbrain is homologous to that of the spinal cord, and its vascular system can be analyzed at the longitudinal and axial structures. During... (Review)
Review
[Anatomical Variations to the Vertebral Artery and Posterior Inferior Cerebellar Artery are Associated with the Partial Persistence of Primitive Lateral Basirovertebral Anastomosis].
The angioarchitecture of the hindbrain is homologous to that of the spinal cord, and its vascular system can be analyzed at the longitudinal and axial structures. During embryonic development, there are two main longitudinal arteries: the longitudinal neural artery and the primitive lateral basilovertebral anastomosis. Commonly observed variations are formed by the fenestration and duplication of either the vertebrobasilar artery, or cerebellar artery, which can be observed when the primitive lateral basilovertebral anastomosis partially persists. Understanding the pattern and development of blood supply to the hindbrain provides useful information of various anomalies in the vertebrobasilar junction and cerebellar arteries.
Topics: Humans; Vertebral Artery; Cerebellum; Male; Female
PubMed: 38783493
DOI: 10.11477/mf.1436204943 -
Scientific Reports May 2024Repetitive transcranial magnetic stimulation (rTMS) for alleviating negative symptoms and cognitive dysfunction in schizophrenia commonly targets the left dorsolateral...
Repetitive transcranial magnetic stimulation (rTMS) for alleviating negative symptoms and cognitive dysfunction in schizophrenia commonly targets the left dorsolateral prefrontal cortex (LDLPFC). However, the therapeutic effectiveness of rTMS at this site remains inconclusive and increasingly, studies are focusing on cerebellar rTMS. Recently, prolonged intermittent theta-burst stimulation (iTBS) has emerged as a rapid-acting form of rTMS with promising clinical benefits. This study explored the cognitive and neurophysiological effects of prolonged iTBS administered to the LDLPFC and cerebellum in a healthy cohort. 50 healthy participants took part in a cross-over study and received prolonged (1800 pulses) iTBS targeting the LDLPFC, cerebellar vermis, and sham iTBS. Mixed effects repeated measures models examined cognitive and event-related potentials (ERPs) from 2-back (P300, N200) and Stroop (N200, N450) tasks after stimulation. Exploratory non-parametric cluster-based permutation tests compared ERPs between conditions. There were no significant differences between conditions for behavioural and ERP outcomes on the 2-back and Stroop tasks. Exploratory cluster-based permutation tests of ERPs did not identify any significant differences between conditions. We did not find evidence that a single session of prolonged iTBS administered to either the LDLPFC or cerebellum could cause any cognitive or ERP changes compared to sham in a healthy sample.
Topics: Humans; Male; Transcranial Magnetic Stimulation; Female; Adult; Cerebellum; Executive Function; Prefrontal Cortex; Evoked Potentials; Young Adult; Healthy Volunteers; Cross-Over Studies; Theta Rhythm; Cognition; Dorsolateral Prefrontal Cortex
PubMed: 38782921
DOI: 10.1038/s41598-024-61404-9 -
ENeuro Jun 2024The Cre-lox system is an indispensable tool in neuroscience research for targeting gene deletions to specific cellular populations. Here we assess the utility of several...
The Cre-lox system is an indispensable tool in neuroscience research for targeting gene deletions to specific cellular populations. Here we assess the utility of several transgenic lines, along with a viral approach, for targeting cerebellar Purkinje cells (PCs) in mice. Using a combination of a fluorescent reporter line () to indicate -mediated recombination and a floxed Dystroglycan line ( ), we show that reporter expression does not always align precisely with loss of protein. The commonly used line exhibits a gradual mosaic pattern of recombination in PCs from Postnatal Day 7 (P7) to P14, while loss of Dag1 protein is not complete until P30. drives recombination in precursor cells that give rise to GABAergic neurons in the embryonic cerebellum, including PCs and molecular layer interneurons. However, due to its transient expression in precursors, results in stochastic loss of Dag1 protein in these neurons. , which is often described as a "pan-neuronal" line for the central nervous system, does not drive -mediated recombination in PCs. We identify a line that drives efficient and complete recombination in embryonic PCs, resulting in loss of Dag1 protein before the period of synaptogenesis. -mediated delivery of at P0 results in gradual transduction of PCs during the second postnatal week, with loss of Dag1 protein not reaching appreciable levels until P35. These results characterize several tools for targeting conditional deletions in cerebellar PCs at different developmental stages and illustrate the importance of validating the loss of protein following recombination.
Topics: Animals; Purkinje Cells; Integrases; Mice, Transgenic; Mice; Recombination, Genetic; Alleles; Gene Deletion; Cerebellum; Mice, Inbred C57BL; Transcription Factors
PubMed: 38777609
DOI: 10.1523/ENEURO.0149-24.2024 -
Revista Da Associacao Medica Brasileira... 2024In this study, the effects of leptin, cannabinoid-1 (CB1) receptor agonist ACEA and antagonist AM251, and the interactions between leptin and CB1 receptor...
OBJECTIVE
In this study, the effects of leptin, cannabinoid-1 (CB1) receptor agonist ACEA and antagonist AM251, and the interactions between leptin and CB1 receptor agonist/antagonist on oxidant and antioxidant enzymes in the cerebrum, cerebellum, and pedunculus cerebri tissue samples were investigated in the penicillin-induced epileptic model.
METHODS
Male Wistar albino rats (n=56) were included in this study. In anesthetized animals, 500 IU penicillin-G potassium was injected into the cortex to induce epileptiform activity. Leptin (1 μg), ACEA (7.5 μg), AM251 (0.25 μg), and the combinations of the leptin+ACEA and leptin+AM251 were administered intracerebroventricularly (i.c.v.) after penicillin injections. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels were measured in the cerebral tissue samples and plasma with the ELISA method.
RESULTS
MDA levels increased, while SOD and GPx levels decreased after penicillin injection in the cerebrum and cerebellum. The efficacy of penicillin on SOD, MDA and GPx levels was further enhanced after leptin or AM251 injections. Whereas, ACEA decreased the MDA levels and increased GPx levels compared with the penicillin group. Administration of AM251+leptin did not change any oxidation parameter compared with the AM251. Furthermore, co-administration of ACEA and leptin significantly increased oxidative stress compared with the ACEA-treated group by increasing MDA and decreasing GPx levels.
CONCLUSION
It was concluded that leptin reversed the effect of ACEA on oxidative stress. Co-administration of AM251 and leptin did not change oxidative stress compared with the AM251-treated group suggesting AM251 and leptin affect oxidative stress using the same pathways.
Topics: Animals; Leptin; Male; Rats, Wistar; Receptor, Cannabinoid, CB1; Epilepsy; Malondialdehyde; Superoxide Dismutase; Piperidines; Pyrazoles; Glutathione Peroxidase; Arachidonic Acids; Rats; Oxidative Stress; Disease Models, Animal; Penicillins; Cerebellum; Cerebrum; Enzyme-Linked Immunosorbent Assay; Cannabinoid Receptor Agonists
PubMed: 38775505
DOI: 10.1590/1806-9282.20231333 -
Neurology Jun 2024
Topics: Humans; Synkinesis; Pons; Male; Demyelinating Diseases; Magnetic Resonance Imaging; Female; Abducens Nerve Diseases; Middle Aged
PubMed: 38771991
DOI: 10.1212/WNL.0000000000209542