1.KIF17 Modulates Epileptic Seizures and Membrane Expression of the NMDA Receptor Subunit NR2B.
Yan LIU ; Xin TIAN ; Pingyang KE ; Juan GU ; Yuanlin MA ; Yi GUO ; Xin XU ; Yuanyuan CHEN ; Min YANG ; Xuefeng WANG ; Fei XIAO
Neuroscience Bulletin 2022;38(8):841-856
Epilepsy is a common and severe brain disease affecting >65 million people worldwide. Recent studies have shown that kinesin superfamily motor protein 17 (KIF17) is expressed in neurons and is involved in regulating the dendrite-targeted transport of N-methyl-D-aspartate receptor subtype 2B (NR2B). However, the effect of KIF17 on epileptic seizures remains to be explored. We found that KIF17 was mainly expressed in neurons and that its expression was increased in epileptic brain tissue. In the kainic acid (KA)-induced epilepsy mouse model, KIF17 overexpression increased the severity of epileptic activity, whereas KIF17 knockdown had the opposite effect. In electrophysiological tests, KIF17 regulated excitatory synaptic transmission, potentially due to KIF17-mediated NR2B membrane expression. In addition, this report provides the first demonstration that KIF17 is modified by SUMOylation (SUMO, small ubiquitin-like modifier), which plays a vital role in the stabilization and maintenance of KIF17 in epilepsy.
Animals
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Epilepsy/metabolism*
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Kinesins/metabolism*
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Mice
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Neurons/metabolism*
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Receptors, N-Methyl-D-Aspartate/metabolism*
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Seizures/metabolism*
2.Forebrain NMDA receptor 2B subunit over-expression has no influence on anxiety behaviors of mice..
Shi-Jia LI ; Min-Hua XU ; Chun-Xia LI ; Tian-Shu ZHOU ; Bo MENG ; Bing MEI
Acta Physiologica Sinica 2009;61(3):272-278
It has been known that the glutamate transmission system and N-methyl-D-aspartate receptor (NMDA-R) were possibly related to anxiety processes. Although anxiety symptom can be relieved by NMDA-R antagonists and partial agonists treatment, the functions of NMDA-R and its subunits in anxiety behaviors remain unclear. We used forebrain specific NR2B over-expression mice to examine whether the increase of NR2B subunit level would induce anxiety behaviors. The results indicated that the juvenile (3-5 months old), middle-aged (8-10 months old) and old (19-22 months old ) NR2B transgenic mice showed no significant difference in open field test and elevated plus maze test as compared with the control mice. Capillary electrophoresis of monoamine neurotransmitter in subregions of forebrain revealed no significant difference between transgenic and control mice of 16-18 months age. These results suggest that the increase of NR2B expression and followed NR1 and NR2A expression augmentations in the forebrain have no significant effect on anxiety-related behaviors in mice.
Animals
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Anxiety
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metabolism
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Mice
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Mice, Transgenic
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Prosencephalon
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metabolism
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Receptors, N-Methyl-D-Aspartate
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metabolism
3.The roles of GluN3-containing N-methyl-D-aspartate receptor in central nerve system.
Qi SUN ; Wei CAO ; Jianhong LUO
Journal of Zhejiang University. Medical sciences 2021;50(5):651-658
The N-methyl-D-aspartate receptor (NMDAR) in central nerve system is mostly composed of GluN1 and GluN2 subunits. The classical NMDAR has been intensively studied. However, GluN3‑containing NMDAR is much less expressed and have atypical channel properties. Recently, accumulating evidences have revealed two types of GluN3‑containing NMDAR: glutamate-gated GluN1/GluN2/GluN3 NMDAR and glycine-gated GluN1/GluN3 NMDAR. The former may play important roles in regulating synapse maturation and pruning non-used synapses, and its elevated expression at the adult stage may alter synaptic reorganization in some neuropsychiatric disorders. The latter is expressed in the medial habenula and involves in control of aversion. This article reviews the recent progresses on the expression, functional properties of GluN3‑containing atypical NMDARs and the physiological and pathological relevance.
Central Nervous System/metabolism*
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Protein Subunits/metabolism*
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Receptors, N-Methyl-D-Aspartate
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Synapses
4.Mechanism of NMDA receptor-dependent neuronal survival and neuroprotection.
Song DO ; Jian-hong LUO ; Shuang QIU
Journal of Zhejiang University. Medical sciences 2011;40(4):440-445
NMDA (N-methyl-D-aspartate) receptors are a subtype of glutamate receptor, and play an important role in both synaptic transmission and synaptic plasticity. When excessively excited, NMDA receptors can cause cell death in many neuropathological scenarios such as OGD (oxygen and glucose deprivation) and brain injury. However, recent studies have revealed that under the physical and some pathological conditions, NMDA receptor could promote neuronal survival and protect neurons from damage.
Neurons
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metabolism
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physiology
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Receptors, N-Methyl-D-Aspartate
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metabolism
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physiology
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Synaptic Transmission
5.Advances in N-methyl-D-aspartate Receptor Signaling Pathway and Mechanism of the Pathway-mediated Apoptosis.
Yi-Xiao HAN ; Ya-Zhu HOU ; Hai-Feng YAN ; Shuai WANG ; Xian-Liang WANG ; Jing-Yuan MAO
Acta Academiae Medicinae Sinicae 2022;44(1):149-157
N-methyl-D-aspartate receptor (NMDAR),an important ionic glutamate receptor and a ligand and voltage-gated ion channel characterized by complex composition and functions and wide distribution,plays a key role in the pathological and physiological process of diseases or stress states.NMDAR can mediate apoptosis through different pathways such as mitochondrial and endoplasmic reticulum damage,production of reactive oxygen species and peroxynitrite,and activation of mitogen-activated protein kinase and calpain.This paper reviews the structure,distribution,and biological characteristics of NMDAR and the mechanisms of NMDAR-mediated apoptosis.
Apoptosis
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Humans
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Mitogen-Activated Protein Kinases/metabolism*
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Reactive Oxygen Species/metabolism*
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Receptors, N-Methyl-D-Aspartate/metabolism*
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Signal Transduction
6.Effects of chronic hypoxic hypercapnia on spatial learning-memory and expression of NMDAR1 in rats.
Song-fang CHEN ; Sheng-min SHAO ; Zhi-pen WU ; Han-jin HUANG ; Xiao-tong WANG ; Li-yong ; Yong-sheng GONG ; Guo-qing ZHENG
Chinese Journal of Applied Physiology 2007;23(4):434-437
AIMTo explore the effect of chronic hypoxic hypercapnia on learning-memory and the possible mechanisms involved.
METHODSFifty-eight male SD rats were randomly divided into three groups: Normal control group (NC, n=18), 2-week (2HH, n=18), and 4-week hypoxic hypercapnia (4HH, n=20) group. The rats, spatial learning-memory tasks were assessed by the Morris water maze. The expression of NMDAR1mRNA was determined by hybridization in situ.
RESULTSCompared with NC group, rats exposed to chronic hypoxic hypercapnia displayed significant impairment in their performance assessed by two measures: mean escape latencies (2HH: 38.59 +/- 8.35 s, 4HH: 60.59 +/- 17.28 s) and swim path distances(2HH: 9893.45 +/- 1958.16 mm, 4HH: 18077.57 +/- 6878.85 mm). The expression level of NMDAR1mRNA in the hippocampus and cortex were lower than those in the NC group, especially, the NMDAR1mRNA expression of hippocampus CA1 in 4HH decreased by 21.4% (P < 0.01).
CONCLUSIONChronic hypoxic hypercapnia could impair the rat spatial learning-memory and the decrease in expression of NMDAR1mRNA might be involved in.
Animals ; Hypercapnia ; metabolism ; Hypoxia ; metabolism ; Male ; Maze Learning ; Memory ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism
7.Roles and expressions of the NMDA receptor subunits (NR2A and NR2B) in visual cortex area of kittens with the normal visual development and anisometropic amblyopia.
Haiwei LI ; Longqian LIU ; Xuyang LIU
Journal of Biomedical Engineering 2011;28(2):264-267
In order to understand the roles of the other subunits, we investigated expression of the NMDA receptor subunits (NR2A and NR2B) in visual cortex of normal and anisometropic amblyopia kittens with different ages in the present study. We examined the expressions of NR2A and NR2B in the visual cortex of the kittens by immunohistochemistry with polyclonal anti-NR2A antibody and anti-NR2B antibody, respectively. Using immunohisto-chemical Streptavidin Perosidase (SP) method, we observed the dynamic changes of NR2A and NR2B with microscope and computer-assisted image analyses. We found that NR2A and NR2B remained low expression after the peak of the critical period of kitten visual development; compared with normal group of the same age, NR2A expresses low. However, the difference is not significant for NR2B before maturation period of visual development. NR2B rises after the maturation period of visual development. According to this, the component of NR2A and NR2B can be affected by anisometropia. This research suggests that the difference of NR2A and NR2B expressions may affect the formation of amblyopia.
Amblyopia
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metabolism
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Animals
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Cats
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Female
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Male
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Receptors, N-Methyl-D-Aspartate
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genetics
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metabolism
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Vision, Ocular
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physiology
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Visual Cortex
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metabolism
8.Expression of NR2A in rat auditory cortex after sound insulation and auditory plasticity.
Yin XIA ; Haishan LONG ; Demin HAN ; Shusheng GONG ; Li LEI ; Jinfeng SHI ; Erzhong FAN ; Ying LI ; Qing ZHAO
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2009;23(11):508-512
OBJECTIVE:
To study the changes of N-methyl-D-aspartate (NMDA) receptor subunit 2A (NR2A) expression at local synapses in auditory cortices after early postnatal sound insulation and tone exposure.
METHOD:
We prepared highly purified synaptosomes from primary auditory cortex by Optiprep flotation gradient centrifugations, and compared the differences of NR2A expression in sound insulation PND14, PND28, PND42 and Tone exposure after sound insulation for 7 days by Western blotting.
RESULT:
The results showed that the NR2A protein expression of PND14 and PND28 decreased significantly (P<0.05). Tone exposure after sound insulation for 7 days, mSIe NR2A protein level increased significantly (P<0.05). It showed bidirectional regulation of NR2A protein. No significant effects of sound insulation and lone exposure were found on the relative expression level of NR2A of PND42 (P>0.05).
CONCLUSION
The results indicate that sound insulation and experience can modify the protein expression level of NR2A during the critical period of rat postnatal development. These findings provide important data for the study on the mechanisms of the developmental plasticity of sensory functions.
Acoustic Stimulation
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Animals
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Auditory Cortex
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metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, N-Methyl-D-Aspartate
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metabolism
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Synapses
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metabolism
10.Forebrain NMDA receptors contribute to neuronal spike responses in adult mice.
Acta Physiologica Sinica 2006;58(6):511-520
Glutamate is the major fast excitatory transmitter in the central nervous system. While normal synaptic transmission is mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors, N-methyl-D-aspartate (NMDA) receptors are thought to selectively contribute to plasticity. Genetically enhancing NMDA receptor functions enhances animal behavior in normal physiological learning and enhances their sensitivity in the case of tissue injury. One major mechanism for NMDA receptors is synaptic long-term potentiation (LTP). Here we present evidence that NMDA receptors not only contribute to normal synaptic responses induced by stimulation of local layer V or white matters, but also contribute to generation of action potentials induced by a depolarizing step applied to the soma. Calcium-calmodulin sensitive adenylyl cyclase 1 and cAMP signal pathways likely mediate these effects. Considering the importance of cingulate neurons in nociception and pain, our results provide a new mechanism for NMDA receptor contributing to neuronal synaptic transmission, spiking properties in forebrains, and possible forebrain-related behavioral nociceptive responses and pain.
Action Potentials
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Adenylyl Cyclases
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metabolism
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Animals
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Cyclic AMP
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metabolism
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Mice
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Prosencephalon
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physiology
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Receptors, N-Methyl-D-Aspartate
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physiology