Asymmetric accumulation of hippocampal 7S SNARE complexes occurs regardless of kindling paradigm

Matveeva, Elena A.; Vanaman, Thomas C.; Whiteheart, Sidney W.; Slevin, John T.

doi:10.1016/j.eplepsyres.2006.11.003

Cited by 36 publications

(51 citation statements)

References 61 publications

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“…Neither of these sample characteristics had an impact on the group differences observed herein. It is possible that differences in life experience (hospitalization, social interaction, active psychosis) could contribute to SNARE alterations, as SNARE expression and complexes can be modified by neuronal activity (Davis et al, 1998;Matveeva et al, 2007). The SNARE protein-protein interactions, observed in this study, were likely formed in vitro, and the relationship to SNARE mechanisms in living patients is uncertain.…”

Section: Possible Limitationsmentioning

confidence: 83%

A Novel Mechanism and Treatment Target for Presynaptic Abnormalities in Specific Striatal Regions in Schizophrenia

Barakauskas

Beasley

Barr

et al. 2010

Neuropsychopharmacol

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Abnormalities of amount and function of presynaptic terminals may have an important role in the mechanism of illness in schizophrenia. The SNARE proteins (SNAP-25, syntaxin, and VAMP) are enriched in presynaptic terminals, where they interact to form a functional complex to facilitate vesicle fusion. SNARE protein amounts are altered in the cortical regions in schizophrenia, but studies of proteinprotein interactions are limited. We extended these investigations to the striatal regions (such as the nucleus accumbens, ventromedial caudate (VMC), and dorsal caudate) relevant to disease symptoms. In addition to measuring SNARE protein levels, we studied SNARE protein-protein interactions using a novel ELISA method. The possible effect of antipsychotic treatment was investigated in parallel in the striatum of rodents that were administered haloperidol and clozapine. In schizophrenia samples, compared with controls, SNAP-25 was 32% lower (P ¼ 0.015) and syntaxin was 26% lower (P ¼ 0.006) in the VMC. In contrast, in the same region, SNARE protein-protein interactions were higher in schizophrenia (P ¼ 0.008). Confocal microscopy of schizophrenia and control VMC showed qualitatively similar SNARE protein immunostaining. Haloperidol treatment of rats increased levels of SNAP-25 (mean 24%, P ¼ 0.003), syntaxin (mean 18%, P ¼ 0.010), and VAMP (mean 16%, P ¼ 0.001), whereas clozapine increased only the VAMP level (mean 13%, P ¼ 0.004). Neither drug altered SNARE protein-protein interactions. These results indicate abnormalities of amount and interactions of proteins directly related to presynaptic function in the VMC in schizophrenia. SNARE proteins and their interactions may be a novel target for the development of therapeutics.

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Section: Possible Limitationsmentioning

confidence: 83%

A Novel Mechanism and Treatment Target for Presynaptic Abnormalities in Specific Striatal Regions in Schizophrenia

Barakauskas

Beasley

Barr

et al. 2010

Neuropsychopharmacol

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“…As seen previously, there was an ipsilateral increase in 7SC, but there was no significant genotype‐specific difference (note that both ratios are above one in both genotypes suggesting only a kindling effect). Similarly, total levels of SV2 increased and NSF decreased in both kindled Tom +/+ and Tom −/− mice, as previously reported for other kindling models (Matveeva et al., 2007; Ohno et al., 2009). There was no significant genotype‐specific difference as seen by the fact the NSF and SV2 levels for both genotypes are below one and above one, respectively, again suggesting only a kindling effect.…”

Section: Resultsmentioning

confidence: 99%

“…This result was not as robust as our previous findings in several kindling models where we saw changes in these protein complexes in the hippocampi of both kindled rats and mice (Matveeva et al., 2007, 2011, 2012). In mice we observed minor, yet significant, increases in SV2 with minimal changes in NSF while observing more robust alterations in the 7SC (Matveeva et al., 2011).…”

Section: Discussionmentioning

confidence: 99%

“…A random sampling from each group of treated animals was processed for histological analysis to assess electrode placement. Surgery specifics have been described previously (Matveeva, Vanaman, Whiteheart, & Slevin, 2007; Slevin & Ferrara, 1985). …”

Section: Methodsmentioning

confidence: 99%

“…If no changes in protein level occur, then the ratio should be one. Note these methods are based on the previously published work (Matveeva et al., 2007). …”

Section: Methodsmentioning

confidence: 99%

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Linking kindling to increased glutamate release in the dentate gyrus of the hippocampus through the STXBP5/tomosyn‐1 gene

et al. 2017

Self Cite

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IntroductionIn kindling, repeated electrical stimulation of certain brain areas causes progressive and permanent intensification of epileptiform activity resulting in generalized seizures. We focused on the role(s) of glutamate and a negative regulator of glutamate release, STXBP5/tomosyn‐1, in kindling.MethodsStimulating electrodes were implanted in the amygdala and progression to two successive Racine stage 5 seizures was measured in wild‐type and STXBP5/tomosyn‐1−/− (Tom−/−) animals. Glutamate release measurements were performed in distinct brain regions using a glutamate‐selective microelectrode array (MEA).ResultsNaïve Tom−/− mice had significant increases in KCl‐evoked glutamate release compared to naïve wild type as measured by MEA of presynaptic release in the hippocampal dentate gyrus (DG). Kindling progression was considerably accelerated in Tom−/− mice, requiring fewer stimuli to reach a fully kindled state. Following full kindling, MEA measurements of both kindled Tom+/+ and Tom−/− mice showed significant increases in KCl‐evoked and spontaneous glutamate release in the DG, indicating a correlation with the fully kindled state independent of genotype. Resting glutamate levels in all hippocampal subregions were significantly lower in the kindled Tom−/− mice, suggesting possible changes in basal control of glutamate circuitry in the kindled Tom−/− mice.ConclusionsOur studies demonstrate that increased glutamate release in the hippocampal DG correlates with acceleration of the kindling process. Although STXBP5/tomosyn‐1 loss increased evoked glutamate release in naïve animals contributing to their prokindling phenotype, the kindling process can override any attenuating effect of STXBP5/tomosyn‐1. Loss of this “braking” effect of STXBP5/tomosyn‐1 on kindling progression may set in motion an alternative but ultimately equally ineffective compensatory response, detected here as reduced basal glutamate release.

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Altered balance between excitatory and inhibitory inputs onto CA1 pyramidal neurons from SV2A‐deficient but not SV2B‐deficient mice

Venkatesan

Alix

Marquet

et al. 2012

J of Neuroscience Research

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Synaptic vesicle protein 2 (SV2) is a glycoprotein that exists in three isoforms, SV2A, SV2B, and SV2C. SV2A knockout (KO) mice and SV2A/SV2B double KO (DKO) mice, but not SV2B KO animals, start to experience severe seizures and weight loss 7 days after birth and die at about postnatal day (P)14-P23. Because excitatory and inhibitory inputs play a major role in controlling neuronal excitability in the hippocampus, we examined the effects of SV2A and/or SV2B deletions on glutamatergic and GABA(A) neurotransmission in hippocampal CA1 pyramidal neurons. Spontaneous and miniature excitatory and inhibitory postsynaptic currents (sEPSCs, mEPSCs, sIPSCs, and mIPSCs, respectively) were recorded using the whole-cell patch-clamp technique in slices from P6-P14 mice. The frequency of sEPSCs was increased in SV2A KO and SV2A/SV2B DKO mice, but their amplitude was unchanged. Such changes were not observed in SV2B KOs. On the contrary, the frequency and amplitude of sIPSCs were decreased in SV2A KO and SV2A/SV2B DKO mice but not in SV2B KO animals, as reported previously for the CA3 region. Kinetic parameters of sIPSCs and sEPSCs were unchanged. Importantly, no changes were observed in any genotype when examining mEPSCs and mIPSCs. We conclude that action potential- and Ca(2+) -dependent glutamatergic and GABAergic synaptic transmission are differentially altered in the hippocampus of SV2A-deficient mice, whereas the mechanism of exocytosis itself is not changed. The altered balance between these major excitatory and inhibitory inputs is probably a contributing factor to seizures in SV2A KO and SV2A/SV2B DKO mice.

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Asymmetric accumulation of hippocampal 7S SNARE complexes occurs regardless of kindling paradigm

Cited by 36 publications

References 61 publications

A Novel Mechanism and Treatment Target for Presynaptic Abnormalities in Specific Striatal Regions in Schizophrenia

A Novel Mechanism and Treatment Target for Presynaptic Abnormalities in Specific Striatal Regions in Schizophrenia

Linking kindling to increased glutamate release in the dentate gyrus of the hippocampus through the STXBP5/tomosyn‐1 gene

Altered balance between excitatory and inhibitory inputs onto CA1 pyramidal neurons from SV2A‐deficient but not SV2B‐deficient mice

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