TOP一般演題(口述)
 
一般演題(口述)
Mental Disorders・Drug Dependence Disorders
1O3-01
Brain dopamine D1 receptor bindings in young adults with autism spectrum disorder
Suzuki Katsuaki1,Ouchi Yasuomi2,Takebayashi Kiyokazu1,Yokokura Masamichi1,Nakaizumi Kyoko1,Nakamura Kazuhiko3,Tsujii Masatsugu4,Sugiyama Toshirou5,Mori Norio1,4
1Dept. Psychiatry, Hamamatsu Univ. Sch. Med.,2Med. Photo. Res. Cent., Hamamatsu Univ. Sch. of Med.,3Dept. NeuroPsychiatry, Hirosaki Univ. Grad. Sch. of Med.,4RCCMD, Hamamatsu Univ. Sch. of Med.,5Dept. Child Adole Psychiatry, Hamamatsu Univ. Sch. of Med.

Autism spectrum disorder(ASD)is characterized by repetitive and/or obsessive interests and behavior and by deficits in sociability and communication. A previous neuroimaging study using positron emission tomography(PET)indicated that dopamine transporter bindings were significantly higher in the orbitofrontal cortex of adults with ASD, although the details remain unknown.
In this study, we measured the binding of dopamine D1-like receptors with the radio-ligand 11C-SCH23390 in the brain of subjects with ASD(n=20)and age- and sex-matched control subjects(n=20). Whole-brain voxel-based analyses as well as regions of interest-based methods were used for between-subject analysis and within-subject correlation analysis with respect to clinical variables.
Both voxel- and region of interest-based analyses revealed significantly higher 11C-SCH23390 binding potentials, in the orbitofrontal cortex of subjects with ASD than in those of controls(corrected P<.05). There was no statistically significant correlation between orbitofrontal 11C-SCH23390 binding potential and any of ASD symptoms evaluated.
The results suggest that a dopaminergic dysregulation in the orbitofrontal cortex, which may play a role in pathophysiology of ASD, can be observed in adult subjects with ASD.
1O3-02
Differential roles of dopamine D1 and D2 receptor-containing neurons of the nucleus accumbens shell in behavioral sensitization
Kai Nobuyuki1,2,Nishizawa Kayo2,Tsutsui Yuji3,Ueda Shuichi1,Kobayashi Kazuto2
1Department of Histology and Neurobiology,2Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University,3Faculty of Symbiotic Systems Science, Fukushima University

The nucleus accumbens(Nac)mediates the reinforcing and motor stimulating properties of psychostimulants. It receives dopaminergic afferents from the ventral midbrain and is divided into two distinct subregions:shell and core. Each of these contains two subtypes of medium spiny neurons, which express either dopamine D1(D1R)or D2(D2R)receptors. However, functional dissociation between the two subtypes in psychostimulant response remains to be elucidated. We performed selective ablation of each subtype in the Nac shell in mice, using immunotoxin-mediated cell targeting, and examined the behavioral sensitization evoked by repeated administration of methamphetamine(METH). The D1R cell-targeted mice exhibited delayed induction of sensitized locomotion compared to control mice, whereas the D2R cell-targeted mice showed a mildly enhanced rate of induction of sensitization. In vivo microdialysis revealed a marked blockade of the increase in extracellular dopamine in the Nac of the D1R cell-targeted animals in response to METH, indicating that the observed delay in behavioral sensitization in these mice involves an impairment in accumbal dopamine release. Our results reveal differential roles of D1R- and D2R-containing accumbal shell neurons in the development of behavioral sensitization to psychostimulants.
1O3-03
Molecular Mechanisms of Fear Memory:Hippocampal Interneurons and their Relevance for Post Traumatic Stress Disorder
Stork Oliver,Caliskan Guersel,Mueller Iris,Albrecht Anne
Department of Genetics & Molecular Neurobiology, Institute of Biology, Otto-von-Guericke University Magdeburg

Pavlovian fear conditioning is an established learning paradigm that allows to study neural mechanisms of fear and anxiety in various species and that may be employed to emulate specific aspects of anxiety disorders. We investigated, in mice, molecular and physiological processes in the amygdalo-hippocampal system that are involved in the consolidation and reconsolidation of such long-term fear memory. GABAergic interneurons are of critical importance for these processes, as indicated by the hyperarousal, fear generalization and deficit in fear extinction of mice deficient for the key enzyme in GABA synthesis, glutamic acid decarboxylase 65. We found that a single reactivation of fear memory in mice is sufficient to trigger long lasting changes in contextual fear, anxiety and endogenous corticosterone levels. With high resolution gene expression we identified changes in gene expression of GABAergic and glutamatergic receptors the CA3 subfield of the hippocampus under these conditions. These molecular changes are accompanied by corticosterone-sensitive alterations in gamma frequency oscillations as well as sharp wave ripple activities measured in hippocampal slice preparations of behaviorally stimulated animals. Both types of network activity patterns are generated by a group of parvalbumin-positive basket cells in the hippocampus. Indeed, genetic enhancement of the activity of these fast spiking interneurons resulted in increased sharp wave ripple propagation in hippocampal slice preparations and enhanced reconsolidation of contextual fear memory at the expense of fear extinction. Together, our data demonstrate the role of a group of GABAergic interneurons in the hippocampus in the development of pathological fear memory and its physiological network correlates.
1O3-04
Prenatal administration of valproic acid or SAHA alters the development of Purkinje cell dendrites and network formation in rat cerebellum
Yoshida Sachiko1,Fueta Yukiko2,Ueno Susumu3,Sekino Yuko4
1Department of Environmental and Life Sciences, Toyohashi University of Technology,2Department of Environmental Management and Control, University of Occupation al and Environmental Health,3Department of Occupational Toxicology, University of Occupational and Enviro nmental Health,4National Institute of Health Sciences

Valproate(VPA), the popular antiepileptic drug, is known as an inducer of autism. It has many kinds of physiological properties, including the inhibition of histone deacetylase(HDAC). Now we investigated the effects of administration of VPA or other HDAC inhibitors to fetus and observed their postnatal cerebellar development. Each HDACi drug was administrated to embryonic day 16 p.o. (VPA;600mg/kg of mother weight, trichostatin A, TSA;0.05mg/kg, MS-275;4mg/kg)or i.p. (suberoylanilide hydroxamic acid, SAHA;60mg/kg).
In cerebellar development, the soma of Purkinje cells form a single layer and elongate their dendrites with synapses during the first two weeks. ATP release was drastically increased from P9 in response to synaptogenesis between Purkinje cells and granule cells. In VPA administrated rat, the elongation of Purkinje cell dendrites started earlier and reached all over the molecular layer even in P12. It was observed also in SAHA administrated rat, while it was obscure in MS-275 or TSA administrated rat. In addition, in VPA or SAHA administrated rat, ATP release became earlier and larger than normal cerebellar development. Some network components would be changed by prenatal HDACi administration. It was suggested that HDACi-induced epigenetic effects would change the developmental progress in immature cerebellum.
1O3-05
Analyses of the pathological roles of the altered brain cytoarchitectures with ectopic neurons
Kubo Ken-ichiro1,Ishii Kazuhiro1,Endo Toshihiro2,Yoshida Keitaro3,Benner Seico2,Ito Yukiko4,Aizawa Hidenori4,Aramaki Michihiko1,Yamanaka Akihiro5,Tanaka Kohichi4,Takata Norio3,Tanaka Kenji3,Mimura Masaru3,Tohyama Chiharu2,Kakeyama Masaki2,6,Nakajima Kazunori1
1Dept. Anatomy, Keio Univ. Sch. Med.,2Lab. of Env. Health Sci., Cent. Dis. Biol. & Integr. Med., Grad. Sch. Med., Univ. of Tokyo,3Dept. Neuropsy., Keio Univ. Sch. Med.,4Lab. of Mol. Neurosci., Med. Res. Inst., Tokyo Med. & Dent. Univ.,5Dept. of Neurosci. II, Res. Inst. of Environmental Med., Nagoya Univ.,6Lab. for Systems Neurosci. & Prev. Med., Faculty of Human Sci., Waseda Univ.

Altered brain cytoarchitectures have been pointed out as one of the neuropathological features of neuropsychiatric disorders, such as schizophrenia and autism, but their pathological roles have not yet been completely understood. To reveal the pathological mechanisms of the altered brain cytoarchitectures, we generated mouse models with ectopic neurons by inducing focal heterotopias with the in utero electroporation technique. The mice with focal heterotopias in the somatosensory cortex exhibited spatial working memory deficit and low competitive dominance behavior, which have been shown to be related to the activity of the medial prefrontal cortex(mPFC)in rodents. Analysis of the mPFC activity revealed that the immediate-early gene expression was decreased and the local field potentials(LFPs)of the mPFC were altered in the mice with heterotopias as compared to the control mice. Moreover, activation of these ectopic and overlying sister neurons mitigated the deficits observed in the mice with heterotopias. These findings suggest that cortical regions containing focal heterotopias can affect distant brain regions and give rise to behavioral abnormalities. Based on these observations, the pathological mechanisms of the altered brain cytoarchitectures with ectopic neurons will be discussed.
1O3-06
Multivariate consideration with social, thermal ambient and bio-molecular interactions suggested new developmental models between common marmosets and humans
Koshiba Mamiko1,2,3,5,Karino Genta1,2,3,Mimura Koki5,Shukuya Masanori4,Nakamura Shun3,Murakoshi Takayuki1,Kunikata Tetsuya2,Yamanouchi Hideo2
1Biochem. Saitama Med. Univ.,2Pediatrics. Saitama Med. Univ.,3Tokyo Univ. A&T,4Tokyo City Univ.,5NCNP

Statistical development in multivariate analyses is potentially accompanied by a large variety of challenging application to imply neuronal complex systems, such as psycho-cognitive functions. In the real world, not only ideal mechanisms studied in laboratories but also multiple kinds of factors interactively influence on one another. To explore computational approaches to infer neuropsychological mechanisms, we have examined several kinds of multivariate analyses whether they could suggest any interplay information or not, particularly in our focusing on emotional development through behavioral and physiological dynamics in two primate species, humans and common marmosets. Given the global rise in autism and other developmental disorders, we hypothesized that critical periods of social learning must be key roles and that parent-infant interactions and socializing with peers shape fundamental nervous system processes, including cognition and emotion. Furthermore, we paid attention what affect the development are not only social environments but together ambient factors for instance, thermal regulation, around individuals every day. We derived the seasonal and gravity factors to be considered. In the trials with multivariate analyses including the principal component analysis, we obtained expressive models visualizing developmental regression curves with repeatedly observed inflection at the similar age stage in common marmosets(Callithrix jacchus). The application to human children also seemed to suggest some essential changes in the summarized complex analytic information dependently on biological and physical environments. They might be able to translate non-verbal descriptions of psycho-cognitive neuronal modulations as understandable complex systems.