OBJECTIVE: To clarify the functional effects of differential expression of ring finger and tryptophan-aspartic acid 2 (RFWD2) on dendritic development and formation of dendritic spines in cerebral cortex neurons of mice. METHODS: Immunofluorescent staining was used to identify the location and global expression profile of RFWD2 in mouse brain and determine the co-localization of RFWD2 with the synaptic proteins in the cortical neurons. We also examined the effects of RFWD2 over-expression (RFWD2-Myc) and RFWD2 knockdown (RFWD2-shRNA) on dendritic development, dendritic spine formation and synaptic function in cultured cortical neurons. RESULTS: RFWD2 is highly expressed in the cerebral cortex and hippocampus of mice, and its expression level was positively correlated with the development of cerebral cortex neurons and dendrites. RFWD2 expression was detected on the presynaptic membrane and postsynaptic membrane of the neurons, and its expression levels were positively correlated with the length, number of branches and complexity of the dendrites. In cultured cortical neurons, RFWD2 overexpression significantly lowered the expressions of the synaptic proteins synaptophysin (P < 0.01) and postsynapic density protein 95 (P < 0.01), while RFWD2 knockdown significantly increased their expressions (both P < 0.05). Compared with the control and RFWD2-overexpressing cells, the neurons with RFWD2 knockdown showed significantly reduced number of dendritic spines (both P < 0.05). CONCLUSION RFWD2 can regulate the expression of the synaptic proteins, the development of the dendrites, the formation of the dendritic spines and synaptic function in mouse cerebral cortex neurons through ubiquitination of Pea3 family members and c-Jun, which may serve as potential treatment targets for neurological diseases.
Animals ; Aspartic Acid/metabolism* ; Cerebral Cortex ; Dendritic Spines/metabolism* ; Mice ; Neurons/metabolism* ; Synapses ; Tryptophan/metabolism*

Volume transmission (VT) is a widespread mode of intercellular communication that occurs in the extracellular fluid (ECF) and in the cerebrospinal fluid (CSF) of the brain with VT signals moving from source to target cells via energy gradients leading to diffusion and convection (flow). The VT channels are diffuse forming a plexus in the extracellular space, while in wiring transmission (WT) the channels (axons, terminals) are private. The speed is slow (seconds-minutes) in VT while rapid in the millisecond range in WT. The extracellular space is the substrate for VT, which is modulated by the extracellular matrix. Extrasynaptic VT is linked to synaptic transmission and likely often takes place due to incomplete diffusion barriers with the synaptic transmitter reaching extrasynaptic domains of the pre-and post-synaptic membrane of the synapse, the astroglia, and even adjacent synapses. Indications exist for the existence of striatal D2-like receptor-mediated extrasynaptic form of dopamine (DA) VT at the local circuit level in vivo in the human striatum. Synaptic glutamate via extrasynaptic VT can act on extrasynaptic metabotropic glutamate receptors located on the astroglia leading to Ca(2+) mediated astrocytic glutamate release into the extracellular space (ECS). Long distance peptide VT and CSF VT is the major long distance VT with distances more than 1 mm and flow in the CSF. Indications for long distance VT of beta-endorphin and oxytocin are obtained. We propose that monogamy in the female prairie vole may take place through an increase in oxytocin VT, especially in nucleus accumbens. Release of extracellular vesicles containing receptors, proteins, RNAs and mtDNA from cellular networks in the central nervous system (CNS) into the ECF and CSF may be a fundamental communication in the CNS. It represents a special form of volume transmission, the Roamer subtype of VT. It may greatly contribute to dynamic events of synaptic plasticity but also to spread of pathological proteins in protein conformational disorders. VT also occurs in the peripheral nervous system and associated cells. Short and long distance VT may take place in meridian channels via diffusion and flow in the interstitial fluid. Acupuncture can produce VT signals by releasing transmitters and modulators from nerve terminals and mast cells.
Animals ; Cell Communication ; Central Nervous System ; cytology ; Extracellular Space ; metabolism ; Humans ; Synapses ; metabolism

Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell (IHC). This feature is believed to be critical for audition over a wide dynamic range, but whether the spatial gradient of ribbon morphology is fine-tuned in each IHC and how the mitochondrial network is organized to meet local energy demands of synaptic transmission remain unclear. By means of three-dimensional electron microscopy and artificial intelligence-based algorithms, we demonstrated the cell-wide structural quantification of ribbons and mitochondria in mature mid-cochlear IHCs of mice. We found that adjacent IHCs in staggered pairs differ substantially in cell body shape and ribbon morphology gradient as well as mitochondrial organization. Moreover, our analysis argues for a location-specific arrangement of correlated ribbon and mitochondrial function at the basolateral IHC pole.
Animals ; Artificial Intelligence ; Cochlea/metabolism* ; Hair Cells, Auditory, Inner ; Mice ; Mitochondria ; Synapses/metabolism*

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* ; Protein Subunits/metabolism* ; Receptors, N-Methyl-D-Aspartate ; Synapses

OBJECTIVE: To observe the GluR2 expression in rat inferior colliculus (IC) in different developmental stages, and to investigate its developmental change and relationship with the synapse development. METHOD: The expression of GluR2 and synaptophysin(SYP) in IC were detected by double immunofluorescence method. RESULT: (1) All sorts of neurons in IC expressed GluR2 in every postnatal groups, and the GluR2 expression in P6w groups was higher than that in other groups. (2) The expression of GluR2 were different in different subnucleus of IC. (3) All sorts of neurons in IC expressed SYP in every postnatal groups, and the SYP expression in P6w groups was higher than others. (4) The expressions of GluR2 consistent with the expression of SYP in IC. CONCLUSION The developmental changes of GluR2 and SYP expression in the rat IC may be involved in the development and plasticity of auditory center.
Animals ; Hypothalamus ; cytology ; metabolism ; Inferior Colliculi ; growth & development ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, AMPA ; metabolism ; Synapses ; metabolism ; Synaptophysin ; metabolism

After changing its language from Korean or English to English only in 2010, the journal metrics of Diabetes & Metabolism Journal (DMJ) were analyzed to assess whether this change in the journal policy was successful. The journal metric items that were analyzed were the following: impact factor; total citations; countries of authors; proportion of the articles funded out of the total number of original articles; and Hirsch-index (H-index). A retrospective, descriptive analysis was carried out using various databases, such as KoreaMed, Korean Medical Citation Index (KoMCI), KoreaMed Synapse, Web of Science, and Journal Citation Ranking. The journal's impact factor was 2.054, which corresponds to 83/122 (68.0%) out of the 2012 JCR endocrinology and metabolism category. The number of the journal's total citations was 330 in 2013. In addition to Korean authors, authors from 13 other countries published papers in the journal from 2010 to 2013. The number of funded papers from 2010 to 2013 was 65 out of 148 original articles (43.9%). The journal's H-index from KoreaMed Synapse was 7, and that from Web of Science was 9. It can be concluded that changing the journal's language to English was successful based on journal metrics. DMJ is currently positioned as an international journal based on the international diversity of authors and editors, its sufficiently high proportion of funded articles, its relatively high impact factor, and the number of total citations.
Bibliometrics ; Databases, Bibliographic ; Endocrinology ; Financial Management ; Journal Impact Factor ; Korea ; Metabolism* ; Retrospective Studies ; Synapses

Alzheimer Disease/pathology* ; Animals ; C9orf72 Protein/metabolism* ; Mice ; Microglia/pathology* ; Neuronal Plasticity ; Neurons/pathology* ; Synapses/pathology*

Aging ; Animals ; Brain ; drug effects ; metabolism ; Calcium ; metabolism ; Female ; Isoflavones ; pharmacology ; Male ; Mice ; Mice, Inbred Strains ; Synapses ; drug effects ; metabolism

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 ; Animals ; Auditory Cortex ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Synapses ; metabolism

AIMTo investigate the neuroprotective effect of learning on glutamate-induced neuronal damage.

METHODSSD rats were intraperitoneally injected with monosodium glutamate (MSG) during the period of 3-9 days after born, and were trained to find their food by light-dark discrimination at 1 month old or 2 months old. At 3 months old, all rats were killed and their brains were taken out and cut into sections and ultrathin sections. The survival neurons in hippocampus were counted under light microscope, and under electric microscope, the ultrastructure, the numbers of synapses and the length of synaptic active zone in fields CA1 of hippocampus were observed.

RESULTSThe survival neurons in field CA3 and CA4, the number of synapses and the length of synaptic active zone in field CA1 of hippocampus increased in learning group than non-learning group.

CONCLUSIONThese finding indicate that discriminative learning can alleviate neuronal injury of hippocampus induced by MSG.

Animals ; Cell Death ; Glutamic Acid ; toxicity ; Hippocampus ; drug effects ; metabolism ; Learning ; Male ; Rats ; Rats, Sprague-Dawley ; Synapses ; metabolism