• Applied Microscopy
• /
• v.25 no.1
• /
• pp.1-14
• /
• 1995

The purpose of this study was to investigate the main sensory trigeminal nucleus in the aging rat brain by means of electron microscope. Male Sprague-Dawley rats, two (control group) and thirty six (aging group) months of age, were used. These animals were sacrificed by perfusion fixation with 2.5% glutaraldehyde-2.0% paraformaldehyde (0.1M phosphate buffer, pH 7.4) under sodium pentobarbital. The objective area was punched out with a sharp-edged metal cylinder of 0.8 mm in diameter. These blocks of tissue were then washed in 0.1M phosphate buffer, postfixed in 2% osmium tetroxide, dehydrated in a graded series of ethyl alcohol, and embedded in Epon 812. Thin sections were cut with Super Nova ultramicrotome, pick up on grids and double stained with lead citrate and uranyl acetate, and observed in JEOL 100B electron microscope. The results were as follows: 1. In the control group, the neuronal cell body of the main sensory trigeminal nucleus was filled with nucleus, Golgi complex, Nissl substance, mitochondria, microfilaments and microtubules. However, few Nissl substances are seen in neuronal cell body. Axoaxonic synapse, axodendritic synapse, axosomatic synapse, axospinous synapse, myelinated and unmyelinated nerve fibers were well organized around cell bodies. Neurons with abnormal changes were not seen. 2. In the aging group, the neuronal cell body of the main sensory trigeminal nucleus contained large number of lipofuscin granules, dense body and swollen mitochondria. Terminal boutons contained glycogen, crystal-like vesicle and membranous indicating first signs of degeneration. The dendrites were found to be in synaptic contact with altered axon terminals. Frequently axons filled with dark axoplasn and splitted myelin sheath were noticed.

• Journal of Educational Research in Mathematics
• /
• v.20 no.1
• /
• pp.21-43
• /
• 2010

In this article three types of neuro-biological epistemology have been studied and applied to mathematics. Nativism or innatism is favored by many evolutionary psychologists and some mathematicians. They believe domain specific brain functions or modules, particularly language faculty and number instinct in infants. Number/mathematical cognition is a new research area and scientists try to localize areas related with mathematics. Selectionism has adopted Darwinism to synapse growth and supports neuronal regression. Mathematical creativity can be explained using selectionism. Neural constructivism has originated from J. Piaget and supports neuronal/synapse growth in children or adults if adequate exercise and practise is given. Unlike Piaget, neural constructivists accepts the importance of structured experience for the reorganization of brain. Authors opinion is all these theories of epistemology is equally important and they all give insights on how the brain and self is made.

• Molecules and Cells
• /
• v.40 no.7
• /
• pp.485-494
• /
• 2017

Oleanolic acid (OA) has neurotrophic effects on neurons, although its use as a neurological drug requires further research. In the present study, we investigated the effects of OA and OA derivatives on the neuronal differentiation of rat hippocampal neural progenitor cells. In addition, we investigated whether the class II histone deacetylase (HDAC) 5 mediates the gene expression induced by OA. We found that OA and OA derivatives induced the formation of neurite spines and the expression of synapse-related molecules. OA and OA derivatives stimulated HDAC5 phosphorylation, and concurrently the nuclear export of HDCA5 and the expression of HDAC5 target genes, indicating that OA and OA derivatives induce neural differentiation and synapse formation via a pathway that involves HDAC5 phosphorylation.

• Molecules and Cells
• /
• v.37 no.7
• /
• pp.511-517
• /
• 2014

MicroRNAs are non-coding short (~23 nucleotides) RNAs that mediate post-transcriptional regulation through sequence-specific gene silencing. The role of miRNAs in neuronal development, synapse formation and synaptic plasticity has been highlighted. However, the role of neuronal activity on miRNA regulation has been less focused. Neuronal activity-dependent regulation of miRNA may finetune gene expression in response to synaptic plasticity and memory formation. Here, we provide an overview of miRNA regulation by neuronal activity including high-throughput screening studies. We also discuss the possible molecular mechanisms of activity-dependent induction and turnover of miRNAs.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.15 no.4
• /
• pp.281-301
• /
• 1993

It was revealed that the morphology and projection pattern of terminal arbors from single primary afferent are different among distinct fiber types, functional types and the different subdivision of trigeminal sensory nucleus complex(TSNC). But it was not identified the ultrastructural morphology and synaptic connections of terminal arbors from each primary afferent within TSNC. So we employed the intra-axonal horseradish peroxidase(HRP) injection technique to define the terminal arbors of primary afferent fiber from slowly adapting mechanoreceptors in the periodontal ligament of the cat, and examined 66 labeled terminal arbors within the rostrodorsomedial part(Vo.r) of the trigeminal nucleus oralis, electromicroscopically with 90nm serial sections. All the boutons labelled with HRP contained clear, spherical and uniform sized synaptic vesicles(diameter : $47.66{\pm}3.58nm$ ). Most of the labelled boutons were boutons en passant type and they were connected by unmyelinated axonal strand. In which neurofilament and microtubule was not developed but occasionally contained synaptic vesicle in contrast to the myelinated axon. The size of the labelled bouton was relatively small(long diameter : $1.46{\pm}0.24{\mu}m$, short diameter $0.85{\pm}0.26{\mu}m$, average diameter $1.15{\pm}0.24{\mu}m$) and the shape of which varied from dome to elongated shape, but scalloped glomerulus shape was not developed. Each primary ending in Vo.r made synapse with one or two neuronal propiles(average : $1.11{\pm}0.31$), of which, 89.4% of labelled boutons made synapse with only one neuronal pro pile, the remainder, 10.6% of labelled boutons, made synapse with two neuronal propile. So characteristically they made very simple synapse. Most of labelled boutons(80.03%) made asymmetrical synapse only with dendritic shaft or spine, and 6.1% of labelled boutons received symmetrical synapse from pleomorphic vesicle containing axonal ending(p-ending). So presynaptic inhibiton was relatively scarce. Synaptic triad, in which a p-ending is presynaptic both pre-and post-synaptic element of the axo-dendritic contact from the labelled primary ending was not observed.

• BMB Reports
• /
• v.48 no.5
• /
• pp.249-255
• /
• 2015

PTPRT/RPTPρ is the most recently isolated member of the type IIB receptor-type protein tyrosine phosphatase family and its expression is restricted to the nervous system. PTPRT plays a critical role in regulation of synaptic formation and neuronal development. When PTPRT was overexpressed in hippocampal neurons, synaptic formation and dendritic arborization were induced. On the other hand, knockdown of PTPRT decreased neuronal transmission and attenuated neuronal development. PTPRT strengthened neuronal synapses by forming homophilic trans dimers with each other and heterophilic cis complexes with neuronal adhesion molecules. Fyn tyrosine kinase regulated PTPRT activity through phosphorylation of tyrosine 912 within the membrane-proximal catalytic domain of PTPRT. Phosphorylation induced homophilic cis dimerization of PTPRT and resulted in the inhibition of phosphatase activity. BCR-Rac1 GAP and Syntaxin-binding protein were found as new endogenous substrates of PTPRT in rat brain. PTPRT induced polymerization of actin cytoskeleton that determined the morphologies of dendrites and spines by inhibiting BCR-Rac1 GAP activity. Additionally, PTPRT appeared to regulate neurotransmitter release through reinforcement of interactions between Syntaxin-binding protein and Syntaxin, a SNARE protein. In conclusion, PTPRT regulates synaptic function and neuronal development through interactions with neuronal adhesion molecules and the dephosphorylation of synaptic molecules. [BMB Reports 2015; 48(5): 249-255]

• BMB Reports
• /
• v.52 no.5
• /
• pp.304-311
• /
• 2019

The cytoplasmic FMR1-interacting protein family (CYFIP1 and CYFIP2) are evolutionarily conserved proteins originally identified as binding partners of the fragile X mental retardation protein (FMRP), a messenger RNA (mRNA)-binding protein whose loss causes the fragile X syndrome. Moreover, CYFIP is a key component of the heteropentameric WAVE regulatory complex (WRC), a critical regulator of neuronal actin dynamics. Therefore, CYFIP may play key roles in regulating both mRNA translation and actin polymerization, which are critically involved in proper neuronal development and function. Nevertheless, compared to CYFIP1, neuronal function and dysfunction of CYFIP2 remain largely unknown, possibly due to the relatively less well established association between CYFIP2 and brain disorders. Despite high amino acid sequence homology between CYFIP1 and CYFIP2, several in vitro and animal model studies have suggested that CYFIP2 has some unique neuronal functions distinct from those of CYFIP1. Furthermore, recent whole-exome sequencing studies identified de novo hot spot variants of CYFIP2 in patients with early infantile epileptic encephalopathy (EIEE), clearly implicating CYFIP2 dysfunction in neurological disorders. In this review, we highlight these recent investigations into the neuronal function and dysfunction of CYFIP2, and also discuss several key questions remaining about this intriguing neuronal protein.

• Molecules and Cells
• /
• v.43 no.6
• /
• pp.551-571
• /
• 2020

Nuclear receptor-related 1 (Nurr1) protein has been identified as an obligatory transcription factor in midbrain dopaminergic neurogenesis, but the global set of human NURR1 target genes remains unexplored. Here, we identified direct gene targets of NURR1 by analyzing genome-wide differential expression of NURR1 together with NURR1 consensus sites in three human neural stem cell (hNSC) lines. Microarray data were validated by quantitative PCR in hNSCs and mouse embryonic brains and through comparison to published human data, including genome-wide association study hits and the BioGPS gene expression atlas. Our analysis identified ~40 NURR1 direct target genes, many of them involved in essential protein modules such as synapse formation, neuronal cell migration during brain development, and cell cycle progression and DNA replication. Specifically, expression of genes related to synapse formation and neuronal cell migration correlated tightly with NURR1 expression, whereas cell cycle progression correlated negatively with it, precisely recapitulating midbrain dopaminergic development. Overall, this systematic examination of NURR1-controlled regulatory networks provides important insights into this protein's biological functions in dopamine-based neurogenesis.

• Korean Journal of Biological Psychiatry
• /
• v.17 no.3
• /
• pp.119-126
• /
• 2010

Synaptic adhesion molecules mediate synapse formation, maturation and maintenance. These proteins are localized at synaptic sites in neuronal axons and dendrites. These proteins function as a bridge of synaptic cleft via interaction with another synaptic adhesion molecules in the opposite side. They can interact with scaffold proteins via intracellular domain and recruit many synaptic proteins, signaling proteins and synaptic vesicles. Scaffold proteins function as a platform in dendritic spines or axonal terminals. Recently, many genetic studies have revealed that synaptic adhesion molecules and scaffold proteins are important in neurodevelopmental disorders, psychotic disorders, mood disorders and anxiety disorders. In this review, fundamental mechanisms of synapse formation and maturation related with synaptic adhesion molecules and scaffold proteins are introduced and their psychiatric implications addressed.

• The Korean Journal of Pain
• /
• v.22 no.1
• /
• pp.1-15
• /
• 2009

Neuropathic pain is often refractory to intervention because of the complex etiology and an incomplete understanding of the mechanisms behind this type of pain. Glial cells, specifically microglia and astrocytes, are powerful modulators of pain and new targets of drug development for neuropathic pain. Glial activation could be the driving force behind chronic pain, maintaining the noxious signal transmission even after the original injury has healed. Glia express chemokine, purinergic, toll-like, glutaminergic and other receptors that enable them to respond to neural signals, and they can modulate neuronal synaptic function and neuronal excitability. Nerve injury upregulates multiple receptors in spinal microglia and astrocytes. Microglia influence neuronal communication by producing inflammatory products at the synapse, as do astrocytes because they completely encapsulate synapses and are in close contact with neuronal somas through gap junctions. Glia are the main source of inflammatory mediators in the central nervous system. New therapeutic strategies for neuropathic pain are emerging such as targeting the glial cells, novel pharmacologic approaches and gene therapy. Drugs targeting microglia and astrocytes, cytokine production, and neural structures including dorsal root ganglion are now under study, as is gene therapy. Isoform-specific inhibition will minimize the side effects produced by blocking all glia with a general inhibitor. Enhancing the anti-inflammatory cytokines could prove more beneficial than administering proinflammatory cytokine antagonists that block glial activation systemically. Research on therapeutic gene transfer to the central nervous system is underway, although obstacles prevent immediate clinical application.