SynapsePub Date : 2022-04-01Epub Date: 2022-02-25DOI: 10.1002/syn.22227
Vasilii Shteinikov, Konstantin Evlanenkov, Konstantin Bolshakov, Denis Tikhonov
{"title":"Glutamate potentiates heterologously expressed homomeric acid-sensing ion channel 1a.","authors":"Vasilii Shteinikov, Konstantin Evlanenkov, Konstantin Bolshakov, Denis Tikhonov","doi":"10.1002/syn.22227","DOIUrl":"https://doi.org/10.1002/syn.22227","url":null,"abstract":"<p><p>Acid-sensing ion channels (ASICs) participate in synaptic transmission due to the acidic content of synaptic vesicles, but their contribution to postsynaptic currents is small. This has stimulated attempts to find endogenous ASIC potentiators that could enhance ASIC-mediated currents to physiologically relevant values. Here we demonstrate that glutamate, which serves as a neurotransmitter, potentiates recombinant ASIC1a in the submillimolar concentration range. The effect of glutamate is especially interesting as ASIC's presence has been shown in glutamatergic synapses. At pH=6.5 glutamate had maximum potentiation of 87% with an EC<sub>50</sub> value of 0.65 mM. The mechanism of potentiation is due to a shift of pH-dependent activation to less acidic values, with 0.5 mM glutamate increasing pH<sub>50</sub> from 6.04 to 6.43. Due to this mechanism, ASIC1a in glutamatergic synapses might be intrinsically potentiated. Furthermore, this effect could compensate for the inhibition of ionotropic glutamate receptors by extracellular acidification during synaptic transmission.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"76 5-6","pages":"e22227"},"PeriodicalIF":2.3,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39624320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SynapsePub Date : 2022-03-06DOI: 10.1002/syn.22231
A. Avendaño-Estrada, L. Verdugo-Dı́az, M. Ávila-Rodríguez
{"title":"Comparative analysis of striatal [18F]FDOPA uptake in a partial lesion model of Parkinson's disease in rats: Ratio method versus graphical model","authors":"A. Avendaño-Estrada, L. Verdugo-Dı́az, M. Ávila-Rodríguez","doi":"10.1002/syn.22231","DOIUrl":"https://doi.org/10.1002/syn.22231","url":null,"abstract":"Animal models of Parkinson's disease are useful to evaluate new treatments and to elucidate the etiology of the disease. Hence, it is necessary to have methods that allow quantification of their effectiveness. [18F]FDOPA‐PET (FDOPA‐PET) imaging is outstanding for this purpose because of its capacity to measure changes in the dopaminergic pathway noninvasively and in vivo. Nevertheless, PET acquisition and quantification is time‐consuming making it necessary to find faster ways to quantify FDOPA‐PET data. This study evaluated Male Wistar rats by FDOPA, before and after being partially injured with 6‐OHDA unilaterally. MicroPET scans with a duration of 120 min were acquired and Patlak reference plots were created to estimate the influx constant Kc in the striatum using the full dynamic scan data. Additionally, simple striatal‐to‐cerebral ratios (SCR) of short static acquisitions were computed and compared with the Kc values. Good correlation (r > 0.70) was obtained between Kc and SCR, acquired between 80–120 min after FDOPA administration with frames of 10 or 20 min and both methods were able to separate the FDOPA‐uptake of healthy controls from that of the PD model (SCR −28%, Kc −71%). The present study concludes that Kc and SCR can be trustfully used to discriminate partially lesioned rats from healthy controls.","PeriodicalId":22131,"journal":{"name":"Synapse","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2022-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44064652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SynapsePub Date : 2022-03-01Epub Date: 2022-02-14DOI: 10.1002/syn.22224
Nathan Gock, Jordan Follett, Gordon L Rintoul, Timothy V Beischlag, Frank J S Lee
{"title":"Endosomal recycling and dopamine neurotransmission: Exploring the links between the retromer and Parkinson's disease.","authors":"Nathan Gock, Jordan Follett, Gordon L Rintoul, Timothy V Beischlag, Frank J S Lee","doi":"10.1002/syn.22224","DOIUrl":"https://doi.org/10.1002/syn.22224","url":null,"abstract":"<p><p>The retromer complex is an evolutionarily conserved protein complex involved in the endosomal recycling of various cargo proteins. It is ubiquitously expressed in all tissue and is found in both invertebrate as well as mammalian nervous systems, where it recycles various synaptic membrane proteins including the dopamine transporter and dopamine D1 receptor, two proteins implicated in dopamine homeostasis and neurotransmission. The involvement of the retromer complex in dopamine neurobiology is further underscored by its links to Parkinson's disease, a neurodegenerative disorder of the dopamine system. In this article, the existing literature linking the retromer complex to synaptic function and dopamine homeostasis is reviewed. Additional possible links are highlighted by exploring the retromer and other Parkinson's disease-associated proteins and possible relationships to synaptic function and dopamine transmission.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"76 3-4","pages":"e22224"},"PeriodicalIF":2.3,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39737540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Does astrocyte gap junction protein expression differ during development in absence epileptic rats?","authors":"Büşra Köse, Mazhar Özkan, İlknur Sur-Erdem, Safiye Çavdar","doi":"10.1002/syn.22225","DOIUrl":"https://doi.org/10.1002/syn.22225","url":null,"abstract":"<p><p>Intercellular communication via gap junctions (GJs) has a wide variety of complex and essential functions in the CNS. In the present developmental study, we aimed to quantify the number of astrocytic GJs protein connexin 30 (Cx30) of genetic model of absence epilepsy rats from Strasbourg (GAERS) at postnatal P10, P30, and P60 days in the epileptic focal areas involved in the cortico-thalamic circuit. We compared the results with Wistar rats using immunohistochemistry and western blotting. The number of Cx30 immunopositive astrocytes per unit area were quantified for the somatosensory cortex (SSCx), ventrobasal (VB), and lateral geniculate (LGN) thalamic nuclei of the two strains and Cx30 western blot was applied to the tissue samples from the same regions. Both immunohistochemical and western blot results revealed the presence of Cx30 in all regions studied at P10 in both Wistar and GAERS animals. The SSCx, VB, and LGN of Wistar animals showed progressive increase in the number of Cx30 immunopositive labeled astrocytes from P10 to P30 and reached a peak at P30; then a significant decline was observed from P30 to P60 for the SSCx and VB. However, in GAERS Cx30 immunopositive labeled astrocytes showed a progressive increase from P10 to P60 for all brain regions studied. The immunohistochemical data highly corresponded with western blotting results. We conclude that the developmental disproportional expression of Cx30 in the epileptic focal areas in GAERS may be related to the onset of absence seizures or may be related to the neurogenesis of absence epilepsy.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"76 3-4","pages":"e22225"},"PeriodicalIF":2.3,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39598913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SynapsePub Date : 2022-02-01Epub Date: 2022-02-14DOI: 10.1002/syn.22223
Kyoungjune Pak, Seongho Seo, Keunyoung Kim, Myung Jun Lee, In Joo Kim
{"title":"SLC6A3 gene polymorphisms are associated with striatal dopamine transporter changes after glucose loading.","authors":"Kyoungjune Pak, Seongho Seo, Keunyoung Kim, Myung Jun Lee, In Joo Kim","doi":"10.1002/syn.22223","DOIUrl":"https://doi.org/10.1002/syn.22223","url":null,"abstract":"<p><p>We investigated the association between SLC6A3 gene polymorphisms and changes in dopamine transporter (DAT) availability after glucose loading in humans. An intravenous injection of <sup>18</sup> F-FP-CIT was administered after infusion of glucose or placebo, and the emission data were acquired over 90 min in 38 healthy male participants. DAT availability expressed in terms of binding potential (BP<sub>ND</sub> ) was recorded. The 40-bp variable number of tandem repeats (VNTR) in the 3' untranslated region and two single nucleotide polymorphisms (SNPs), rs2652511 and rs2937639, in the SLC6A3 gene were genotyped. Among the 38 participants, those with a VNTR other than 10R/10R (n = 7) were excluded. The alleles of the two SNPs (rs2652511 and rs2937639) appeared to be inherited together in two fixed combinations (C-G or T-A) in 29 of 31 individuals. The BP<sub>ND</sub> in the ventral striatum (VST), caudate nucleus, and putamen was not significantly different after glucose or placebo loading according to genotype. However, BP<sub>ND</sub> s from the caudate nucleus and putamen of all participants with rs2652511 CT/rs2937639 AG (n = 6) were higher after glucose loading. In conclusion, the SLC6A3 gene polymorphism is associated with the changes in DAT availability after glucose loading. DAT availability after glucose or placebo loading in the VST, caudate nucleus, and putamen did not differ according to the SLC6A3 genotype.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"76 1-2","pages":"e22223"},"PeriodicalIF":2.3,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39874061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Asymmetrical organization of oral structures in the primary and secondary somatosensory cortices in rats: An optical imaging study.","authors":"Yuki Kirihara, Manabu Zama, Satoshi Fujita, Shouhei Ogisawa, Shuichi Nishikubo, Morio Tonogi, Masayuki Kobayashi","doi":"10.1002/syn.22222","DOIUrl":"https://doi.org/10.1002/syn.22222","url":null,"abstract":"<p><p>In rodents, the representation of the body surface in the primary somatosensory cortex (S1) forms a mirror image along the ventral border of the S1 in the secondary somatosensory cortex (S2). Sensory information from the oral region is processed in the S1 and the border region between the S2 and insular oral region (IOR). We examined the relationship between somatosensory representations in the S1 and S2/IOR using optical imaging with a voltage-sensitive dye in urethane-anesthetized rats. In reference to the rhinal fissure and middle cerebral artery, we made a somatosensory map by applying electrical or air puff stimulation. The initial neural excitation in the S1 to facial structures, including the eyebrow, cornea, pinna, whisker pad, nasal tip, and nasal mucosa, spread toward the ventral area, putatively the S2. The initial cortical responses in the S1 to oral structures, including the lower lip, tongue, and teeth, were spatially separated from those in the S2/IOR. The representation of the tongue center, tongue tip, mandibular molar pulp, mandibular incisor pulp, and mandibular incisor periodontal ligament were almost linearly arranged from caudal to rostral in both S1 and S2/IOR. The lower lip was represented in the dorsal area from the representation of teeth and tongue in both S1 and S2/IOR. The representations of maxillary teeth were caudal and dorsal to the representations of mandibular teeth in the S1 and S2/IOR, respectively. These results suggest that the representation of oral structures in the S1 formed a non-mirror image, not a mirror image, in the S2/IOR.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"76 1-2","pages":"e22222"},"PeriodicalIF":2.3,"publicationDate":"2022-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39824033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of Stat3 in NLRP3/caspase-1-mediated hippocampal neuronal pyroptosis in epileptic mice.","authors":"Qian Jiang, Guo Tang, Xue-Min Zhong, Dan-Rui Ding, Hui Wang, Jia-Ni Li","doi":"10.1002/syn.22221","DOIUrl":"https://doi.org/10.1002/syn.22221","url":null,"abstract":"<p><p>Epilepsy, a fairly common neurological disorder, is linked to various sequelae and greatly impairs the quality of life. Meanwhile, there is evidence to suggest an association between pyroptosis and epilepsy. Accordingly, the current study sought to determine the role of signal transduction activator of transcription 3 (Stat3) in pyroptosis in epileptic mice. First, epileptic mouse models were induced by lithium chloride, atropine, and pilocarpine, and HT22 cells were treated with lipopolysaccharide (LPS) to establish in vitro hippocampal neuronal inflammation models. Subsequently, Stat3, NOD-like receptor protein 3 (NLRP3), cleaved-caspase-1, gasdermin D (GSDMD)-N, activated Stat3 (p-Stat3), and H3K9Ac levels were detected in the mouse hippocampus and HT22 cells. Morris water maze test was further performed to detect changes in the learning and memory abilities of epileptic mice, and hematoxylin-eosin staining and Nissl staining were conducted to detect the pathological injury. HT22 cell proliferation and apoptosis were also detected using a cell counting kit-8 assay and flow cytometry. An enzyme-linked immunosorbent assay was adopted to detect Interleukin (IL)-1β and IL-18 concentrations in the mouse hippocampus and HT22 cells. Furthermore, the enrichment of H3K9Ac and p-Stat3 in the NLRP3 promoter region was detected with the help of a chromatin immunoprecipitation assay. The obtained findings revealed that Stat3 was highly expressed in the hippocampus of epileptic mice and LPS-treated HT22 cells. Meanwhile, Stat3 silencing brought about improvements in the learning and memory abilities of the mice, in addition to alleviation of hippocampal neuronal damage and pyroptosis-related factors in hippocampal tissue and HT22 cells. We also observed that Stat3 bound to the NLRP3 promoter to promote H3K9 acetylation and NLRP3 transcription. Moreover, increasing H3K9Ac in cells annulled the inhibition of silencing Stat3 on neuronal pyroptosis. To conclude, our findings revealed that Stat3 bound to the NLRP3 promoter to augment H3K9 acetylation, NLRP3 transcription, and NLRP3/caspase-1-mediated neuronal pyroptosis, resulting in aggravation of neuronal damage in epileptic mice.</p>","PeriodicalId":22131,"journal":{"name":"Synapse","volume":"75 12","pages":"e22221"},"PeriodicalIF":2.3,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39767441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}