Tanimura A

References (5)

Title : Long-term effect of galantamine on cognitive function in patients with Alzheimer's disease versus a simulated disease trajectory: an observational study in the clinical setting - Nakagawa_2017_Neuropsychiatr.Dis.Treat_13_1115
Author(s) : Nakagawa R , Ohnishi T , Kobayashi H , Yamaoka T , Yajima T , Tanimura A , Kato T , Yoshizawa K
Ref : Neuropsychiatr Dis Treat , 13 :1115 , 2017
Abstract : BACKGROUND: Long-term maintenance of cognitive function is an important goal of treatment for Alzheimer's disease (AD), but evidence about the long-term efficacy of cholinesterase inhibitors is sparse. To evaluate the long-term efficacy and safety of galantamine for AD in routine clinical practice, we conducted a 72-week post-marketing surveillance study. The effect of galantamine on cognitive function was estimated in comparison with a simulated disease trajectory. PATIENTS AND
METHODS: Patients with mild-to-moderate AD received flexible dosing of galantamine (16-24 mg/day) during this study. Cognitive function was assessed by the mini mental state examination (MMSE) and the clinical status was determined by the Clinical Global Impression-Improvement (CGI-I). Changes of the MMSE score without treatment were estimated in each patient using Mendiondo's model. Generalized linear mixed model analysis was performed to compare the simulated MMSE scores with the actual scores.
RESULTS: Of the 661 patients who were enrolled, 642 were evaluable for safety and 554 were assessed for efficacy. The discontinuation rate was 46.73%. Cognitive decline indicated by the mean change of actual MMSE scores was significantly smaller than the simulated decline. Individual analysis demonstrated that >70% of patients had better actual MMSE scores than their simulated scores. Significant improvement of CGI-I was also observed during the observation period. Adverse events occurred in 28.5% of patients and were serious in 8.41%. The reported events generally corresponded with the safety profile of galantamine in previous studies. CONCLUSION: These findings support the long-term efficacy of galantamine for maintaining cognitive function and the clinical state in AD patients. Treatment with galantamine was generally safe. Importantly, this study revealed that galantamine improved cognitive function above the predicted level in >70% of the patients.
ESTHER : Nakagawa_2017_Neuropsychiatr.Dis.Treat_13_1115
PubMedSearch : Nakagawa_2017_Neuropsychiatr.Dis.Treat_13_1115
PubMedID: 28458553

Title : Cholinergic Interneurons Amplify Corticostriatal Synaptic Responses in the Q175 Model of Huntington's Disease - Tanimura_2016_Front.Syst.Neurosci_10_102
Author(s) : Tanimura A , Lim SA , Aceves Buendia JJ , Goldberg JA , Surmeier DJ
Ref : Front Syst Neurosci , 10 :102 , 2016
Abstract : Huntington's disease (HD) is a neurodegenerative disorder characterized by deficits in movement control that are widely viewed as stemming from pathophysiological changes in the striatum. Giant, aspiny cholinergic interneurons (ChIs) are key elements in the striatal circuitry controlling movement, but whether their physiological properties are intact in the HD brain is unclear. To address this issue, the synaptic properties of ChIs were examined using optogenetic approaches in the Q175 mouse model of HD. In ex vivo brain slices, synaptic facilitation at thalamostriatal synapses onto ChIs was reduced in Q175 mice. The alteration in thalamostriatal transmission was paralleled by an increased response to optogenetic stimulation of cortical axons, enabling these inputs to more readily induce burst-pause patterns of activity in ChIs. This adaptation was dependent upon amplification of cortically evoked responses by a post-synaptic upregulation of voltage-dependent Na(+) channels. This upregulation also led to an increased ability of somatic spikes to invade ChI dendrites. However, there was not an alteration in the basal pacemaking rate of ChIs, possibly due to increased availability of Kv4 channels. Thus, there is a functional "re-wiring" of the striatal networks in Q175 mice, which results in greater cortical control of phasic ChI activity, which is widely thought to shape the impact of salient stimuli on striatal action selection.
ESTHER : Tanimura_2016_Front.Syst.Neurosci_10_102
PubMedSearch : Tanimura_2016_Front.Syst.Neurosci_10_102
PubMedID: 28018188

Title : Acute inhibition of diacylglycerol lipase blocks endocannabinoid-mediated retrograde signalling: evidence for on-demand biosynthesis of 2-arachidonoylglycerol - Hashimotodani_2013_J.Physiol_591_4765
Author(s) : Hashimotodani Y , Ohno-Shosaku T , Tanimura A , Kita Y , Sano Y , Shimizu T , Di Marzo V , Kano M
Ref : The Journal of Physiology , 591 :4765 , 2013
Abstract : Abstract The endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) produced by diacylglycerol lipase alpha (DGLalpha) is one of the best-characterized retrograde messengers at central synapses. It has been thought that 2-AG is produced 'on demand' upon activation of postsynaptic neurons. However, recent studies propose that 2-AG is pre-synthesized by DGLalpha and stored in neurons, and that 2-AG is released from such 'pre-formed pools' without the participation of DGLalpha. To address whether the 2-AG source for retrograde signalling is the on-demand biosynthesis by DGLalpha or the mobilization from pre-formed pools, we examined the effects of acute pharmacological inhibition of DGL by a novel potent DGL inhibitor, OMDM-188, on retrograde eCB signalling triggered by Ca2+ elevation, Gq/11 protein-coupled receptor activation or synergy of these two stimuli in postsynaptic neurons. We found that pretreatment for 1 h with OMDM-188 effectively blocked depolarization-induced suppression of inhibition (DSI), a purely Ca2+-dependent form of eCB signalling, in slices from the hippocampus, striatum and cerebellum. We also found that at parallel fibre-Purkinje cell synapses in the cerebellum OMDM-188 abolished synaptically induced retrograde eCB signalling, which is known to be caused by the synergy of postsynaptic Ca2+ elevation and group I metabotropic glutamate receptor (I-mGluR) activation. Moreover, brief OMDM-188 treatments for several minutes were sufficient to suppress both DSI and the I-mGluR-induced retrograde eCB signalling in cultured hippocampal neurons. These results are consistent with the hypothesis that 2-AG for synaptic retrograde signalling is supplied as a result of on-demand biosynthesis by DGLalpha rather than mobilization from presumptive pre-formed pools.
ESTHER : Hashimotodani_2013_J.Physiol_591_4765
PubMedSearch : Hashimotodani_2013_J.Physiol_591_4765
PubMedID: 23858009
Gene_locus related to this paper: human-DAGLA

Title : Complementary synaptic distribution of enzymes responsible for synthesis and inactivation of the endocannabinoid 2-arachidonoylglycerol in the human hippocampus - Ludanyi_2011_Neurosci_174_50
Author(s) : Ludanyi A , Hu SS , Yamazaki M , Tanimura A , Piomelli D , Watanabe M , Kano M , Sakimura K , Magloczky Z , Mackie K , Freund TF , Katona I
Ref : Neuroscience , 174 :50 , 2011
Abstract : Clinical and experimental evidence demonstrates that endocannabinoids play either beneficial or adverse roles in many neurological and psychiatric disorders. Their medical significance may be best explained by the emerging concept that endocannabinoids are essential modulators of synaptic transmission throughout the central nervous system. However, the precise molecular architecture of the endocannabinoid signaling machinery in the human brain remains elusive. To address this issue, we investigated the synaptic distribution of metabolic enzymes for the most abundant endocannabinoid molecule, 2-arachidonoylglycerol (2-AG), in the postmortem human hippocampus. Immunostaining for diacylglycerol lipase-alpha (DGL-alpha), the main synthesizing enzyme of 2-AG, resulted in a laminar pattern corresponding to the termination zones of glutamatergic pathways. The highest density of DGL-alpha-immunostaining was observed in strata radiatum and oriens of the cornu ammonis and in the inner third of stratum moleculare of the dentate gyrus. At higher magnification, DGL-alpha-immunopositive puncta were distributed throughout the neuropil outlining the immunonegative main dendrites of pyramidal and granule cells. Electron microscopic analysis revealed that this pattern was due to the accumulation of DGL-alpha in dendritic spine heads. Similar DGL-alpha-immunostaining pattern was also found in hippocampi of wild-type, but not of DGL-alpha knockout mice. Using two independent antibodies developed against monoacylglycerol lipase (MGL), the predominant enzyme inactivating 2-AG, immunostaining also revealed a laminar and punctate staining pattern. However, as observed previously in rodent hippocampus, MGL was enriched in axon terminals instead of postsynaptic structures at the ultrastructural level. Taken together, these findings demonstrate the post- and presynaptic segregation of primary enzymes responsible for synthesis and elimination of 2-AG, respectively, in the human hippocampus. Thus, molecular architecture of the endocannabinoid signaling machinery supports retrograde regulation of synaptic activity, and its similar blueprint in rodents and humans further indicates that 2-AG's physiological role as a negative feed-back signal is an evolutionarily conserved feature of excitatory synapses.
ESTHER : Ludanyi_2011_Neurosci_174_50
PubMedSearch : Ludanyi_2011_Neurosci_174_50
PubMedID: 21035522

Title : The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission - Tanimura_2010_Neuron_65_320
Author(s) : Tanimura A , Yamazaki M , Hashimotodani Y , Uchigashima M , Kawata S , Abe M , Kita Y , Hashimoto K , Shimizu T , Watanabe M , Sakimura K , Kano M
Ref : Neuron , 65 :320 , 2010
Abstract : Endocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, we generated and analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase alpha (DGLalpha) and beta (DGLbeta). We found that endocannabinoid-mediated retrograde synaptic suppression was totally absent in the cerebellum, hippocampus, and striatum of DGLalpha knockout mice, whereas the retrograde suppression was intact in DGLbeta knockout brains. The basal 2-AG content was markedly reduced and stimulus-induced elevation of 2-AG was absent in DGLalpha knockout brains, whereas the 2-AG content was normal in DGLbeta knockout brains. Morphology of the brain and expression of molecules required for 2-AG production other than DGLs were normal in the two knockout mice. We conclude that 2-AG produced by DGLalpha, but not by DGLbeta, mediates retrograde suppression at central synapses.
ESTHER : Tanimura_2010_Neuron_65_320
PubMedSearch : Tanimura_2010_Neuron_65_320
PubMedID: 20159446
Gene_locus related to this paper: human-DAGLA