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The International Journal of... 2005The brain vesicles that are formed at an early stage of neural development are the fundamentals of the brain plan. Heterotopic transplantation revealed that the... (Review)
Review
The brain vesicles that are formed at an early stage of neural development are the fundamentals of the brain plan. Heterotopic transplantation revealed that the diencephalon could change its fate when juxtaposed to the isthmus (mes-metencephalic boundary), which indicated that the isthmus functions as an organizer for the mesencephalon and metencephalon. Fgf8 is identified as an isthmus organizing signal. Misexpression of Fgf8a and Fgf8b indicated that a strong Fgf8 signal organizes cerebellar development. The transcription factors define the fate of the region. Overlapping expression of Otx2, En1 and Pax2 may define the mesencephalic region and additional expression of Pax3/7 may instruct the mesencephalic region to differentiate into the tectum. The di-mesencephalic boundary is determined by repressive interaction between Pax6 and En1/Pax2 and the mes-metencephalic boundary is defined by repressive interaction between Otx2 and Gbx2. Fgf8 is induced at the border of the Otx2 and Gbx2 expression domain, overlapping with Gbx2 expression.
Topics: Animals; Body Patterning; Brain; Gene Expression Regulation, Developmental; Gene Silencing; Gene Transfer Techniques; Mesencephalon; Metencephalon; Organizers, Embryonic
PubMed: 15906236
DOI: 10.1387/ijdb.041964hn -
Journal of Neurophysiology Dec 2022A hedge fund billionaire's children are suffering from cerebellar disease. He invited a group of neuroscientists to plan a search for therapies. What resulted is the... (Review)
Review
A hedge fund billionaire's children are suffering from cerebellar disease. He invited a group of neuroscientists to plan a search for therapies. What resulted is the outline of an implantable neural emulator that might electronically replace the damaged part of the brain.
Topics: Male; Child; Humans; Purkinje Cells; Cerebellum; Cerebellar Diseases
PubMed: 36350062
DOI: 10.1152/jn.00437.2022 -
Cells Sep 2022The cerebellar reserve is defined as the capacity of the cerebellum for compensation and restoration following injury. This unique cerebellar ability is attributed to...
The cerebellar reserve is defined as the capacity of the cerebellum for compensation and restoration following injury. This unique cerebellar ability is attributed to various forms of synaptic plasticity that incorporate multimodal and redundant cerebellar inputs, two major features of the cerebellar circuitry. It is assumed that the cerebellar reserve is acquired from the age of 12 years after the maturation of both the cerebellar adaptative behaviors and cerebellar functional connectivity. However, acquiring the cerebellar reserve is also affected by two other factors: vulnerability and growth potential in the developing cerebellum. First, cerebellar injury during the critical period of neural circuit formation (especially during fetal and neonatal life and infancy) leads to persistent dysfunction of the cerebellum and its targets, resulting in the limitation of the cerebellar reserve. Secondly, growth potential appears to facilitate cerebellar reserve during the stage when the cerebellar reserve is still immature. Based on these findings, the present mini-review proposes a possible developmental trajectory underlying the acquisition of cerebellar reserve. We highlight the importance of studies dedicated to the understanding of the cerebellar resilience to injuries.
Topics: Cerebellum; Neuronal Plasticity
PubMed: 36230975
DOI: 10.3390/cells11193013 -
International Journal of Molecular... Feb 2024Although more than 30 different types of neuropeptides have been identified in various cell types and circuits of the cerebellum, their unique functions in the... (Review)
Review
Although more than 30 different types of neuropeptides have been identified in various cell types and circuits of the cerebellum, their unique functions in the cerebellum remain poorly understood. Given the nature of their diffuse distribution, peptidergic systems are generally assumed to exert a modulatory effect on the cerebellum via adaptively tuning neuronal excitability, synaptic transmission, and synaptic plasticity within cerebellar circuits. Moreover, cerebellar neuropeptides have also been revealed to be involved in the neurogenetic and developmental regulation of the developing cerebellum, including survival, migration, differentiation, and maturation of the Purkinje cells and granule cells in the cerebellar cortex. On the other hand, cerebellar neuropeptides hold a critical position in the pathophysiology and pathogenesis of many cerebellar-related motor and psychiatric disorders, such as cerebellar ataxias and autism. Over the past two decades, a growing body of evidence has indicated neuropeptides as potential therapeutic targets to ameliorate these diseases effectively. Therefore, this review focuses on eight cerebellar neuropeptides that have attracted more attention in recent years and have significant potential for clinical application associated with neurodegenerative and/or neuropsychiatric disorders, including brain-derived neurotrophic factor, corticotropin-releasing factor, angiotensin II, neuropeptide Y, orexin, thyrotropin-releasing hormone, oxytocin, and secretin, which may provide novel insights and a framework for our understanding of cerebellar-related disorders and have implications for novel treatments targeting neuropeptide systems.
Topics: Humans; Cerebellum; Purkinje Cells; Neurons; Cerebellar Cortex; Neuropeptides; Cerebellar Diseases
PubMed: 38397008
DOI: 10.3390/ijms25042332 -
Journal of Integrative Neuroscience Jan 2022Apoptosis, autophagy and necrosis are the three main types of programmed cell death. One or more of these types of programmed cell death may take place in neurons... (Review)
Review
Apoptosis, autophagy and necrosis are the three main types of programmed cell death. One or more of these types of programmed cell death may take place in neurons leading to their death in various neurodegenerative disorders in humans. Purkinje neurons (PNs) are among the most highly vulnerable population of neurons to cell death in response to intrinsic hereditary diseases or extrinsic toxic, hypoxic, ischemic, and traumatic injury. In this review, we will describe the three main types of programmed cell death, including the molecular mechanisms and the sequence of events in each of them, and thus illustrating the intracellular proteins that mediate and regulate each of these types. Then, we will discuss the role of Ca2+ in PN function and increased vulnerability to cell death. Additionally, PN death will be described in animal models, namely lurcher mutant mouse and shaker mutant rat, in order to illustrate the potential therapeutic implications of programmed cell death in PNs by reviewing the previous studies that were carried out to interfere with the programmed cell death in an attempt to rescue PNs from death.
Topics: Animals; Apoptosis; Autophagy; Cerebellum; Humans; Mice; Necrosis; Neurodegenerative Diseases; Purkinje Cells; Rats
PubMed: 35164466
DOI: 10.31083/j.jin2101030 -
Neuroscience Dec 2020Dexterous forelimb movements like reaching, grasping, and manipulating objects are fundamental building blocks of the mammalian motor repertoire. These behaviors are... (Review)
Review
Dexterous forelimb movements like reaching, grasping, and manipulating objects are fundamental building blocks of the mammalian motor repertoire. These behaviors are essential to everyday activities, and their elaboration underlies incredible accomplishments by human beings in art and sport. Moreover, the susceptibility of these behaviors to damage and disease of the nervous system can lead to debilitating deficits, highlighting a need for a better understanding of function and dysfunction in sensorimotor control. The cerebellum is central to coordinating limb movements, as defined in large part by Joseph Babinski and Gordon Holmes describing motor impairment in patients with cerebellar lesions over 100 years ago (Babinski, 1902; Holmes, 1917), and supported by many important human and animal studies that have been conducted since. Here, with a focus on output pathways of the cerebellar nuclei across mammalian species, we describe forelimb movement deficits observed when cerebellar circuits are perturbed, the mechanisms through which these circuits influence motor output, and key challenges in defining how the cerebellum refines limb movement.
Topics: Animals; Cerebellar Nuclei; Cerebellum; Forelimb; Hand Strength; Humans; Movement
PubMed: 32652173
DOI: 10.1016/j.neuroscience.2020.06.046 -
PLoS Genetics Apr 2020The cerebellum is a pivotal centre for the integration and processing of motor and sensory information. Its extended development into the postnatal period makes this... (Review)
Review
The cerebellum is a pivotal centre for the integration and processing of motor and sensory information. Its extended development into the postnatal period makes this structure vulnerable to a variety of pathologies, including neoplasia. These properties have prompted intensive investigations that reveal not only developmental mechanisms in common with other regions of the neuraxis but also unique strategies to generate neuronal diversity. How the phenotypically distinct cell types of the cerebellum emerge rests on understanding how gene expression differences arise in a spatially and temporally coordinated manner from initially homogeneous cell populations. Increasingly sophisticated fate mapping approaches, culminating in genetic-induced fate mapping, have furthered the understanding of lineage relationships between early- versus later-born cells. Tracing the developmental histories of cells in this way coupled with analysis of gene expression patterns has provided insight into the developmental genetic programmes that instruct cellular heterogeneity. A limitation to date has been the bulk analysis of cells, which blurs lineage relationships and obscures gene expression differences between cells that underpin the cellular taxonomy of the cerebellum. This review emphasises recent discoveries, focusing mainly on single-cell sequencing in mouse and parallel human studies that elucidate neural progenitor developmental trajectories with unprecedented resolution. Complementary functional studies of neural repair after cerebellar injury are challenging assumptions about the stability of postnatal cellular identities. The result is a wealth of new information about the developmental mechanisms that generate cerebellar neural diversity, with implications for human evolution.
Topics: Animals; Cell Differentiation; Cell Lineage; Cerebellum; Humans; Morphogenesis; Neurons; Single-Cell Analysis
PubMed: 32298260
DOI: 10.1371/journal.pgen.1008630 -
Journal of Neurochemistry Jan 2021The Kölliker-Fuse nucleus (KF) is a functionally distinct component of the parabrachial complex, located in the dorsolateral pons of mammals. The KF has a major role in... (Review)
Review
The Kölliker-Fuse nucleus (KF) is a functionally distinct component of the parabrachial complex, located in the dorsolateral pons of mammals. The KF has a major role in respiration and upper airway control. A comprehensive understanding of the KF and its contributions to respiratory function and dysfunction requires an appreciation for its neurochemical characteristics. The goal of this review is to summarize the diverse neurochemical composition of the KF, focusing on the neurotransmitters, neuromodulators, and neuropeptides present. We also include a description of the receptors expressed on KF neurons and transporters involved in each system, as well as their putative roles in respiratory physiology. Finally, we provide a short section reviewing the literature regarding neurochemical changes in the KF in the context of respiratory dysfunction observed in SIDS and Rett syndrome. By over-viewing the current literature on the neurochemical composition of the KF, this review will serve to aid a wide range of topics in the future research into the neural control of respiration in health and disease.
Topics: Animals; Humans; Kolliker-Fuse Nucleus; Respiration
PubMed: 32396650
DOI: 10.1111/jnc.15041 -
Acta Medica Portuguesa 2010Cerebellar hypoplasias are cerebellar malformations with small but completely formed cerebellum. They can be divided in focal and in diffuse or generalized. It is... (Review)
Review
Cerebellar hypoplasias are cerebellar malformations with small but completely formed cerebellum. They can be divided in focal and in diffuse or generalized. It is sometimes difficult to make distinction between cerebellar atrophy (progressive condition) and hipoplasia (not progressive condition). Focal hypoplasias are restricted to one cerebellar hemisphere or to the vermis. Diffuse hypoplasias refer to both cerebellar hemispheres and vermis. If there is associated IVth ventricle enlargement, hypoplasias occur in the context of Dandy-Walker complex, a continuum of posterior fossa cystic anomalies. A revision of cerebellar hypoplasias and associated pathology is done, illustrated with 22 cases tha include focal and diffuse cerebellar hypoplasias, Dandy-Walker malformations and its variant, persistent Blake's pouch cyst, megacisterna magna, PEHO síndrome (progressive encephalopathy with oedema, hipsarrhythmia and optic atrophy), Joubert syndrome, congenital disorder of glycosylation type Ia, pontocerebellar hipoplasias Barth type I and II, diffuse subcortical heterotopia. The imaging finding of structural cerebellar anomalies frequently leads to diagnostic incertainty as the anomalies are mostly unspecific, implying an extenuating analytical and genetic workup. Their knowledge and classification may be useful to decide the patient adjusted laboratorial workup.
Topics: Abnormalities, Multiple; Cerebellum; Humans; Pons
PubMed: 21144325
DOI: No ID Found -
Cerebellum (London, England) Dec 2016The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes... (Review)
Review
The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum.
Topics: Animals; Cerebellum; Consensus; Humans; Neurogenesis; Neurons
PubMed: 26439486
DOI: 10.1007/s12311-015-0724-2