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Abstracts / Neuroscience

3-j3Ø Behavioral and histological examinations in TR-alpha orR-beta deficient miceiyuki Sadamatsu1, Hirohiko Kanai2, Nobumasa Kato3

Department of Psychiatry, Nara Medical University, Kashihara,apan; 2 Department of Psychiatry, Shiga University Medicalcience, Otsu, Japan; 3 Department of Psychiatry, Faculty ofedicine, Showa University, Tokyo, Japan

hyroid functions are well known to participate in neuronal develop-ent after birth in mice. The drug-induced hypothyroidism in a early

eriod of the neuronal development results in permanent behavioralbnormality, including memory disturbance and hyperactivity. However,he relevance of the memory disturbance and the hyperactivity to thy-oid hormone receptors, TR-alpha and TR-beta, remains unknown. Toddress this issue, we performed histological examination and behav-oral experiments, including open field and radial maze in TR-alpha andR-beta deficient mice. In open field experiment, the TR-alpha deficientice exhibited the tendency of hyperactivity, but unexpectedly we did not

bserved any gross behavioral abnormalities in TR-beta deficient mice. Inhis study, we explored the possible involvement of the thyroid hormoneignaling in the development of the brain functions after birth.

3-j32 CtBPs are binding proteins of the novel isoform ofoxP2 lacking forkhead domainriko Fujita1, Ayumi Matsuzaki1,2, Yuko Tanabe1, Tadashiasahara2, Mariko Momoi3, Takashi Momoi1National Institute of Neuroscience, NCNP, Japan; 2 Kyoritsuniversity of Pharmacy, Tokyo, Japan; 3 Jichi Medical University,ochigi, Japan

he mutations of FOXP2 have been detected in the family of thepeech/language disorder. Recently, we identified the forkhead nuclearocalization domains that contribute to the cellular distribution of FOXP2.uclear localization of FOXP2 depended on two distally separateduclear localization signals in the forkhead domain. In contrast with wild-ype, the mutated FOXP2s are located in the cytoplasm. However, we alsodentified the novel isofrom lacking forkhead domain located in the cyto-lasm of Perkinje cells (P2-P10). To examine the biological role of theovel isoform, we tried to isolate the proteins binding with the novel

soform of FOXP2 by yeast-two-hybrid system. Here we show that thissoform specifically binds with CtBPs with multifuctions such as repres-or, golgi fission, and synapticvesicle fusion. The novel isoform may benvolved in the synaptic function via binding with CtBPs.

esearch fund: KAKENHI (18700333).

3-j33 Identification of a novel isoform of Foxp2 located in theytoplasm of mouse developing Purkinje cellsyumi Matsuzaki1,2, Yuko Tanabe1, Eriko Fujita1, Tadashiasahara2, Takashi Momoi1Department of Inherited Metabolic Diseases, NCNP, Tokyo,apan; 2 Department of Biochemistry, Kyoritsu University ofharmacy, Tokyo, Japan

OXP2 belongs to a newly identified subfamily of Forkhead box (FOX)-ranscription factors. The mutations of FOXP2 have been detected in theamily of the speech/language disorder, suggesting that FOXP2 is involvedn acquiring human speech/language ability. In contrast with wild type, the

utated FOXP2s are located in the cytoplasm. In the present study, wedentified the forkhead nuclear localization domains that contribute to theellular distribution of FOXP2. Nuclear localization of FOXP2 depends onwo distally separated nuclear localization signals in the forkhead domain.

urthermore, we identified the novel isofrom lacking forkhead domain

ocated in the cytoplasm during mouse brain development. In the mouseerebellum, this novel isoform was mainly detected in the cytoplasm ofhe Purkinje cells (P2-P10), but not in those of P15-P22. This novel isoform

ay be involved in the acquiring mouse “singing” ability related to theuman speech/language ability.

cbOogo

rch 58S (2007) S1–S244 S239

3-j34 Brain proteins with PDZ domains associated withA175/SynCAMuko Tanabe1, Ayumi Matsuzaki1, Eriko Fujita1, Giulo Piluso2,higeo Ohno3, Shouichi Ishiura4, Alaa Hussein5, Vencenzoigro2, Takashi Momoi1

National Institute of Neuroscience,Tokyo, Japan; 2 Secondaniversity, Napoli, Italy; 3 Yokohama City University Graduatechool of Medical Science; 4 University, Tokyo; 5 University Britisholumbia, Vancouver, BC, Canada

ssociation of neuroligins with PSD-95 and Shank controls the balanceetween neuronal excitation and inhibition. Mutations of neuroligin-3 andhank-3 have been detected in the patient of Autism. RA175/SynCAM,omophilic cell adhesion molecule with PDZ binding domain at C-erminal, is also involved in the formation of functional synapse.A175/SynCAM interacts with CASK at presynapse, but little is knownbout the binding molecules at postsynapse. We examined the RA175C-erminal binding protein in mouse brain by yeast two hybrid analysis andull-down assay. Unlike neuroligin, RA175 directly band with Par-3 andA175 had a complex with Shank but not with PSD-95. RA175 may bessociated with Shank via other scaffolding molecules with PDZ domain.e will discuss this putative complex associated with the autism.

esearch funds: KAKENHI (18700333), Research for Nervous and Mentalisorders (17A-1).

3-j35 Perinatal BPA exposure impairs synaptic architecturesnd functions in the hippocampus of offspringing Chen1, Masahiro Sokabe2,3

Dept Physiol, Nanjing Med Univ, Nanjing, China; 2 Dept Physiol,agoya Univ Grad Sch Med, Nagoya, Japan; 3 ICORP/SORST Cellechanosensing, JST, Nagoya, Japan

umans are routinely exposed to the environmental estrogen bisphenol(BPA) leaking from food and beverage containers. Exposure to low

oses of BPA are known to affect a variety of animal behaviors includ-ng memory and learning. Here we report that perinatal exposure to aow dose of BPA (100 ng/kg) impaired the maze learning, and increasedhe spontaneous motor activities of 4 weeks male offspring. We inves-igated the neuronal functions and ultra-structures of the hippocampalA1 region in these animals. Basal synaptic transmission and populationpikes were significantly enhanced, whereas tetanic LTP was impairedithout changes in the paired-pulse facilitation. Although the density

nd spatial configuration of pyramidal cells looked normal, their spinesnd synaptic contacts at apical dendrites were morphologically altered.hese results suggest that perinatal exposure to BPA will alter the hip-ocampal synaptic architectures and functions, resulting in behavioralbnormalities of the offspring.

3-j36 Effects of mitochondrial ATP-sensitive K channel open-ng during ischemia/reperfusion in neuronsobuhiro Matsuoka1, Shigeyuki Yamada1, Masaaki Shizukuisi1,omiei Kazama1, Yasushi Kobayashi2, Hideyuki Ishida3

Department of Anesthesiology, National Defense Medical College,aitama, Japan; 2 Department of Anatomy and Neurobiology,ational Defense Medical College, Saitama, Japan; 3 Departmentf Physiology, Tokai University, Kanagawa, Japan

e investigated the effect of mitochondrial ATP-sensitive K (mitoKATP)hannel opening on the ability of oxygen glucose deprivation (OGD) torevent intracellular Ca2+ ([Ca2+]i) overload or �ψm depolarization inat hippocampal CA1 pyramidal cells. Acute hippocampal slices werereloaded with [Ca2+]i indicator or �ψm indicator. Simulated ischemiaas performed by subjecting to a 10-min OGD, then slices were recovered

or 5 min. Relative changes in the [Ca2+]i and the�ψm were measured byonfocal system. After OGD the [Ca2+] increased and the�ψ deceased,

i mut both deceased after recovery phase. Ischemic preconditioning (1-minGD) and anti-anginal drug nicorandil dramatically reduced the [Ca2+]iverload and�ψm depolarization resulting from OGD. These results sug-est that mitoKATP channel opening might be attributed to the mechanismf neuroprotection.