• Title/Summary/Keyword: Brain plasticity

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Mammalian target of rapamycin inhibitors for treatment in tuberous sclerosis

  • Kim, Won-Seop
    • Clinical and Experimental Pediatrics
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    • v.54 no.6
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    • pp.241-245
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    • 2011
  • Tuberous sclerosis complex (TSC) is a genetic multisystem disorder that results from mutations in the TSC1 or TSC2 genes, and is associated with hamartomas in several organs, including subependymal giant cell tumors. The neurological manifestations of TSC are particularly challenging and include infantile spasms, intractable epilepsy, cognitive disabilities, and autism. The TSC1- and TSC2-encoded proteins modulate cell function via the mammalian target of rapamycin (mTOR) signaling cascade, and are key factors in the regulation of cell growth and proliferation. The mTOR pathway provides an intersection for an intricate network of protein cascades that respond to cellular nutrition, energy levels, and growth factor stimulation. In the brain, TSC1 and TSC2 have been implicated in cell body size, dendritic arborization, axonal outgrowth and targeting, neuronal migration, cortical lamination, and spine formation. The mTOR pathway represents a logical candidate for drug targeting, because mTOR regulates multiple cellular functions that may contribute to epileptogenesis, including protein synthesis, cell growth and proliferation, and synaptic plasticity. Antagonism of the mTOR pathway with rapamycin and related compounds may provide new therapeutic options for TSC patients.

Synapses in neurodegenerative diseases

  • Bae, Jae Ryul;Kim, Sung Hyun
    • BMB Reports
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    • v.50 no.5
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    • pp.237-246
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    • 2017
  • Synapse is the basic structural and functional component for neural communication in the brain. The presynaptic terminal is the structural and functionally essential area that initiates communication and maintains the continuous functional neural information flow. It contains synaptic vesicles (SV) filled with neurotransmitters, an active zone for release, and numerous proteins for SV fusion and retrieval. The structural and functional synaptic plasticity is a representative characteristic; however, it is highly vulnerable to various pathological conditions. In fact, synaptic alteration is thought to be central to neural disease processes. In particular, the alteration of the structural and functional phenotype of the presynaptic terminal is a highly significant evidence for neural diseases. In this review, we specifically describe structural and functional alteration of nerve terminals in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD).

Worldwide national intervention of developmental screening programs in infant and early childhood

  • Kim, Seunghyo
    • Clinical and Experimental Pediatrics
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    • v.65 no.1
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    • pp.10-20
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    • 2022
  • The prevalence of developmental disabilities is increasing worldwide over time. Developmental issues in infancy or early childhood may cause learning difficulties or behavioral problem in school age, further adversely affecting adolescent quality of life, which finally lead to low socioeconomic status in family, increase in medical expenses, and other relevant issues in various ways. Early childhood has brain plasticity, which means there is a high chance of recovering from developmental issues by early detection and timely intervention. Pediatricians are placed an ideal position to meet with young children till 6 years of age, of which age range is the time applicable to early intervention. Determining child's developmental status can be made by 2 pathways such as developmental surveillance and developmental screening tests. For better results, pediatricians should update their knowledge about developmental issues, risk factors, and screening techniques through varying educational program or other relevant educating materials. This paper will update reports on the prevalence of developmental disabilities and review the recent results of the Korean developmental screening test and discuss relevant issues. Finally, it will be addressed the pediatrician's role in early detecting developmental issues and timely intervention.

Beyond Clot Dissolution; Role of Tissue Plasminogen Activator in Central Nervous System

  • Kim, Ji-Woon;Lee, Soon-Young;Joo, So-Hyun;Song, Mi-Ryoung;Shin, Chan-Young
    • Biomolecules & Therapeutics
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    • v.15 no.1
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    • pp.16-26
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    • 2007
  • Tissue plasminogen activator (tPA) is a serine protease catalyzing the proteolytic conversion of plasminogen into plasmin, which is involved in thrombolysis. During last two decades, the role of tPA in brain physiology and pathology has been extensively investigated. tPA is expressed in brain regions such as cortex, hippocampus, amygdala and cerebellum, and major neural cell types such as neuron, astrocyte, microglia and endothelial cells express tPA in basal status. After strong neural stimulation such as seizure, tPA behaves as an immediate early gene increasing the expression level within an hour. Neural activity and/or postsynaptic stimulation increased the release of tPA from axonal terminal and presumably from dendritic compartment. Neuronal tPA regulates plastic changes in neuronal function and structure mediating key neurologic processes such as visual cortex plasticity, seizure spreading, cerebellar motor learning, long term potentiation and addictive or withdrawal behavior after morphine discontinuance. In addition to these physiological roles, tPA mediates excitotoxicity leading to the neurodegeneration in several pathological conditions including ischemic stroke. Increasing amount of evidence also suggest the role of tPA in neurodegenerative diseases such as Alzheimer's disease and multiple sclerosis even though beneficial effects was also reported in case of Alzheimer's disease based on the observation of tPA-induced degradation of $A{\beta}$ aggregates. Target proteins of tPA action include extracellular matrix protein laminin, proteoglycans and NMDA receptor. In addition, several receptors (or binding partners) for tPA has been reported such as low-density lipoprotein receptor-related protein (LRP) and annexin II, even though intracellular signaling mechanism underlying tPA action is not clear yet. Interestingly, the action of tPA comprises both proteolytic and non-proteolytic mechanism. In case of microglial activation, tPA showed non-proteolytic cytokine-like function. The search for exact target proteins and receptor molecules for tPA along with the identification of the mechanism regulating tPA expression and release in the nervous system will enable us to better understand several key neurological processes like teaming and memory as well as to obtain therapeutic tools against neurodegenerative diseases.

Comparisons of the Plastic Changes in the Central Nervous System in the Processing of Neuropathic Pain (신경병증성 통증의 처리 과정에 있어 중추신경계의 가소성 변화 비교)

  • Kwon, Minjee
    • Science of Emotion and Sensibility
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    • v.24 no.2
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    • pp.39-48
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    • 2021
  • According to International Associating for the Study of Pain (IASP) definition, neuropathic pain is a disorder characterized by dysfunction of the nervous system that, under normal conditions, mediates virulent information to the central nervous system (CNS). This pain can be divided into a disease with provable lesions in the peripheral or central nervous system and states with an incorporeal lesion of any nerves. Both conditions undergo long-term and chronic processes of change, which can eventually develop into chronic pain syndrome, that is, nervous system is inappropriately adapted and difficult to heal. However, the treatment of neuropathic pain itself is incurable from diagnosis to treatment process, and there is still a lack of notable solutions. Recently, several studies have observed the responses of CNS to harmful stimuli using image analysis technologies, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and optical imaging. These techniques have confirmed that the change in synaptic-plasticity was generated in brain regions which perceive and handle pain information. Furthermore, these techniques helped in understanding the interaction of learning mechanisms and chronic pain, including neuropathic pain. The study aims to describe recent findings that revealed the mechanisms of pathological pain and the structural and functional changes in the brain. Reflecting on the definition of chronic pain and inspecting the latest reports will help develop approaches to alleviate pain.

Developmental Switch of the Serotonergic Role in the Induction of Synaptic Long-term Potentiation in the Rat Visual Cortex

  • Park, Sung-Won;Jang, Hyun-Jong;Cho, Kwang-Hyun;Kim, Myung-Jun;Yoon, Shin-Hee;Rhie, Duck-Joo
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.1
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    • pp.65-70
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    • 2012
  • Synaptic long-term potentiation (LTP) and long-term depression (LTD) have been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. Serotonin (5-hydroxytryptamine, 5-HT) inhibits the induction of LTP and LTD during the critical period of the rat visual cortex (postnatal 3~5 weeks). However, in adult rats, the increase in 5-HT level in the brain by the administration of the selective serotonin reuptake inhibitor (SSRI) fluoxetine reinstates ocular dominance plasticity and LTP in the visual cortex. Here, we investigated the effect of 5-HT on the induction of LTP in the visual cortex obtained from 3- to 10-week-old rats. Field potentials in layer 2/3, evoked by the stimulation of underlying layer 4, was potentiated by theta-burst stimulation (TBS) in 3- and 5-weekold rats, then declined to the baseline level with aging to 10 weeks. Whereas 5-HT inhibited the induction of LTP in 5-week-old rats, it reinstated the induction of N-methyl-D-aspartate receptor (NMDA)-dependent LTP in 8- and 10-week-old rats. Moreover, the selective SSRI citalopram reinstated LTP. The potentiating effect of 5-HT at 8 weeks of age was mediated by the activation of 5-$HT_2$ receptors, but not by the activation of either 5-$HT_{1A}$ or 5-$HT_3$ receptors. These results suggested that the effect of 5-HT on the induction of LTP switches from inhibitory in young rats to facilitatory in adult rats.

A Case Report of a patient with hemiplegia ipsilateral to affected cerebral hemisphere (대뇌반구의 병변과 동측에 반신마비 발생한 중풍 환자의 1례)

  • Cho, Seung-yeon;Gwak, Ja-young;Hong, Jin-woo;Na, Byong-jo;Park, seong-uk;Jung, Woo-sang;Moon, Sang-kwan;Park, Jung-mi;Ko, Chang-nam
    • The Journal of the Society of Stroke on Korean Medicine
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    • v.8 no.1
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    • pp.48-57
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    • 2007
  • Stroke is a disease which results in impairment of body functions and affects everyday life. The ability of cerebral neurons to become reorganized and restore function after damage is called plasticity. Motor impairment typically appears contralateral to the affected cerebral hemisphere in patients with cerebral lesions. The authors report a case of a patient with hemiplegia ipsilateral to affected cerebral hemisphere, along with its conjectured mechanism.

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How does stereology help to inform translation from neuroscience to OT? (입체해석학을 통해 신경과학의 정보를 작업치료학에 어떻게 전달할수 있을까?)

  • Park, Ji-Hyuk;Lee, Joo-Hyun;Park, Jin-Hyuck
    • Therapeutic Science for Rehabilitation
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    • v.3 no.2
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    • pp.5-48
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    • 2014
  • Introduction : One of the important domains in OT is performance skills which include sensory perceptual skills, motor and praxis skills, emotional regulation skills, cognitive skills, and communication/social skills. All of these skills are support ed by integrated neurological processes. Body : Stereology robust tool when employed to investigate morphological changes in neurons, cortex area, and specific parts of brain involved in special brain function. Stereology is an interdisciplinary field focused or analyzing biological tissue with the three-dimensional interpretation of planer sections by using estimating method and mathematically unbiased sampling. With the unbiased stereological method based on probability theory, researchers can estimate morphological and anatomical changes in biological reference areas accurately and efficiently. Changes in anatomical and cytoarchitectural parameters, such as volume, number, and length, affect specific brain function related to the brain area. Occupational therapists provide treatment to improve functions for participation of occupation in neurological disorder. The functional improvements in neurological disorder reflect neurobiological changes because functional difficulties, such as motor cognitive disorder, are due to neurological disturbances. Thus, combination of two kinds of evidence, neurological changes and functional improvement, provide fundamental evidence for OT intervention in neurological disorder. Even though most of stereological studies are in animal model and in postmortem human because of practical and ethical issues, stereology provides fundamental knowledge to support OT theory and practice. Conclusion : Therefore, stereology informs translation from neuroscience to OT based on structure-function relationship in performance skills and experience-dependent neural plasticity.

The Evaluation of Cerebral Executive Function Using Functional MRI (기능적 자기공명영상기법을 이용한 대뇌의 집행기능 평가)

  • Eun, Sung Jong;Gook, Jin Seon;Kim, Jeong Jae
    • Journal of the Korean Society of Radiology
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    • v.7 no.5
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    • pp.305-311
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    • 2013
  • This study involves an experiment using functional magnetic resonance imaging(fMRI) to delineate brain activation for execution functional performance. Participates to this experiment of the normal adult (man 4, woman 6) of 10 people, is not inserts the metal all closed phobia and 24.5 year-old average ages which the operating surgeon experience which are not they were. The subject for a functional MRI experiment word -color test prosecuting attorney subject rightly at magnetic pole presentation time of 30 first editions and after presenting, uses SPM 99 programs and the image realignment, after executing a standardization (nomalization), a difference which the signal burglar considers the timely order as lattice does, pixel each image will count there probably is, in order to examine rest and active crossroad dividing independence sample t-test (p<.05). Overlapped in this standard anatomic image and got a brain activation image from level of significance 95%. With functional MRI resultant execution function inside being relation, the prefrontal lobe, anterior cingulate gyrus, parietal lobe, orbitofrontal gyrus, temporal lobe, parietal lobe was activated. The execution function promotes a recovery major role from occupational therapy, understanding about the damage mechanism is important. When confirms the brain active area which accomplishes an execution function brain plasticity develops the cognitive therapeutic method which is effective increases usefully very, will be used.