Kanji Yoshimoto

Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4-phenylbutyrate, a chemical chaperone.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is primarily characterized by the degeneration of dopaminergic neurons in the nigrostriatal pathway. Previous studies have demonstrated that chronic systemic exposure of Lewis rats to rotenone produced many features of PD, and cerebral tauopathy was also detected in the case of severe weight loss. The present study was designed to assess the neurotoxicity of rotenone after daily oral administration for 28u2003days at several doses in C57BL/6 mice. In addition, we examined the protective effects of 4‐phenylbutyrate (4‐PBA) on nigral dopamine (DA) neurons in rotenone‐treated mice. 4‐PBA was injected intraperitoneally daily 30u2003min before each oral administration of rotenone. Chronic oral administration of rotenone at high doses induced specific nigrostriatal DA neurodegeneration, motor deficits and the up‐regulation of α‐synuclein in the surviving DA neurons. In contrast to the Lewis rat model, cerebral tauopathy was not detected in this mouse model. 4‐PBA inhibited rotenone‐induced neuronal death and decreased the protein level of α‐synuclein. These results suggest that this rotenone mouse model may be useful for understanding the mechanism of DA neurodegeneration in PD, and that 4‐PBA has a neuroprotective effect in the treatment of PD.

Alterations in the function of cerebral dopaminergic and serotonergic systems following electroacupuncture and moxibustion applications: possible correlates with their antistress and psychosomatic actions.

Alterations in cerebral monoamines following application of electroacupuncture were investigated using conscious rats with and without application of restraining stress. The dopamine and serotonin levels were significantly decreased in the nucleus accumbens, caudate putamen, and lateral hypothalamus and increased in the dorsal raphe nucleus by restraining stress. On the other hand, application of electroacupuncture on the lumbar and hindlimb segments eliminated the above changes in dopamine, while the changes in serotonin were attenuated by lumbar and hindlimb electroacupuncture. However, the effects of hindlimb electroacupuncture were greater than those of lumbar electroacupuncture. These results clearly indicate that lumbar and hindlimb electroacupuncture stimulations have differential effects on brain monoaminergic neurons in rats exposed to restraining stress. Moxa burning stimulation was applied to the lumbar and hindlimb segments of rats without restraining stress. The dopamine level was significantly increased in the midbrain substantia nigra-ventrotegmental area by hindlimb moxibusion. On the other hand, the serotonin levels were significantly increased in the nucleus amygdala by lumber moxibusion and decreased in the nucleus accumbens by hindlimb moxibusion. The present results indicate that electroacupuncture applied to the lumbar and hindlimb segments has an antistress effect, while the application of moxibustion to the lumbar and hindlimb segments was likely to stimulate the functions of mesocortical and mesolimbic dopaminergic and serotonergic neurons. We suggest that functional alterations in cerebral dopaminergic and serotonergic neurons are involved in the clinical efficacy of electroacupuncture and moxibustion, especially because of their antistress and psychosomatic actions.

Developmental changes in cerebrospinal fluid concentrations of monoamine-related substances revealed with a Coulochem electrode array system.

The relationship between age and cerebrospinal fluid concentrations of monoamine-related substances, including kynurenine, were investigated using a Coulochem electrode array system, to clarify developmental changes in monoamine-related substances in the human central nervous system. In neurologically normal children, significant inverse correlations with age were observed for the cerebrospinal fluid concentrations of 5-hydroxytryptophan, 5-hydroxyindole-acetic acid, kynurenine, homovanillic acid, 3-methoxy-4- hydroxyphenyl glycol, and 3-O-methyl-dopamine. The concentrations of their precursors, tryptophan and tyrosine, were not related to age. This is the first comprehensive study revealing developmental changes in monoamine-related substances including their precursors and metabolites. (J Child Neurol 2000;15:267-270).

Hypothalamic aggression area under serotonergic control in mouse-killing behaviour of rats

The serotonergic system participates in the modulation of aggressive behaviour. We examined the neuronal substrate underlying serotonergic control of aggressive behaviour in rats using a transplantation technique. Fetal serotonergic neurons transplanted into the hypothalamus restored inhibition of mouse-killing behaviour (muricide), in rats with raphe lesions induced by a serotonergic neurotoxin, 5,7-dihydroxytryptamine. Immunohistochemical and neurochemical studies indicated that the recovery of serotonergic innervation in the lateral hypothalamic area by the raphe grafts brought about the inhibition of muricide. The extension of serotonergic fibres into the lateral hypothalamic area from the grafted serotonergic neurons is strongly related to inhibition of muricide. These results indicate the possibility that serotonergic neurons regulate muricide through the inhibition of the activity of the lateral hypothalamic area neurons.

Distribution of 6R-L-Erythro-5,6,7,8-Tetrahydrobiopterin in Regional Brain Areas of Inbred Strains of Rats and Mice with Different Alcohol Preferences

6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) is a coenzyme for tyrosine, tryptophan and phenylalanine hydroxylases, the former two of which are the initial and the rate-limiting enzymes in the biosynthesis of catecholamines and serotonin, respectively. The present study was conducted to determine the levels of 6R-BH4 in the inbred strains of rats BN and F344, and the inbred strains of mice C57BL/6J, C3H/HeJ and DBA/2J, with different genetically determined alcohol preferences. Previous studies have shown that BN and F344 rats exhibit a high and low alcohol preference, respectively; that C57BL/6J and DBA/2J mice show a high and low alcohol preference, respectively, and that C3H/HeJ mice exhibit a moderate alcohol preference. The levels of 6R-BH4 were measured in five regional brain areas of rats and in two regional brain areas of mice. There was about a 3-fold difference in 6R-BH4 levels across the rat brain areas assayed, ranging from a low level in the frontal cortex to a high level in the striatum and midbrain. Midbrain 6R-BH4 levels in F344 rats were higher than those of BN rats (p < 0.05). On the other hand, striatal 6R-BH4 levels in DBA/2J mice were higher than those of the other two strains of mice (p < 0.05). These results indicate that 6R-BH4 is distributed throughout the nigro- and mesostriatal dopaminergic nervous systems, and that brain 6R-BH4 levels may be involved in the genetic differences in alcohol-drinking behavior in animal models.

The Effects of 6R-L-Erythro-5,6,7,8-Tetrahydrobiopterin on Ethanol-Induced Sleep Time and Ethanol Elimination in Inbred Strains of Mice with Different Alcohol Preference

6R-L-erythro-5,6,7,8-tetrahydrobiopterin (6R-BH4) is a coenzyme for tyrosine, tryptophan and phenylalanine hydroxylases. Male C57BL/6J and DBA/2J mice were given 6R-BH4 (0, 12.5, 25.0 and 50.0 mg/kg of body weight, i.v.) or saline, and then 4 h later, all animals were injected with ethanol (EtOH) (4.0 g/kg, i.p.), which causes them to lose the righting reflex, to investigate the differences in EtOH-induced sleeping time. 6R-BH4 pretreatment reduced EtOH-induced sleep time in DBA/2J mice with lower alcohol preference (p < 0.05), which showed no changes in the pharmacokinetics of blood EtOH. No changes in EtOH-induced sleep time were observed in C57BL/6J mice with higher alcohol preference. These results indicate that the sensitivity to EtOH in mice with lower alcohol preference was associated with 6R-BH4 activity in the CNS.

Intrastriatal injection of 6-hydroxydopamine induces impairments of spatial memory and causes excessive expression of ezrin in hippocampus in mice

s / Neuroscience Research 71S (2011) e108–e415 e189 P2-q21 Region specific expression of the defense enzymes MTH1, OGG1 and MUTYH against oxidative damage in nucleic acids in the substantia nigra of mouse Zijing Sheng , Yusaku Nakabeppu Div. Neurofunc. Genomics, MIB, Kyushu Univ., Fukuoka, Japan Oxidative DNA damage has been inferred to be involved in the neurodegenerative pathway of Parkinson’s disease. Dopaminergic neurons are believed to be particularly vulnerable to oxidative stress. To counteract oxidative damage to nucleic acids, human and rodents are equipped with three defense enzymes, MTH1, OGG1 and MUTYH. MTH1 hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP to their monophosphate forms, thus sanitizing nucleotide pools. OGG1, an 8-oxoguanine DNA glycosylase, prevents buildup of 8-oxoguanine in both nuclear and mitochondrial genomes. MUTYH, an adenine DNA glycosylase, excises adenine opposite 8-oxoguanine and 2-hydroxyadenine opposite guanine. Our previous studies showed that MTH1-deficient mice exhibited a greater accumulation of 8-oxoguanine in substantia nigra after MPTP administration (Yamaguchi et al., 2006), indicating that MTH1 plays a protective role in the substantia nigra, however, expression of these enzymes has yet to be clarified in the substantia nigra. In the present study, the expression of MTH1, OGG1 and MUTYH was examined immunohistochemically in the mouse substantia nigra. We found that large number of neurons in the substantia nigra pars compacta (SNc) express MTH1, OGG1 or MUTYH, respectively, whereas only small number of neurons in the ventral tegmental area (VTA) express these enzymes. Double-immunodetection of tyrosine hydroxylase (TH) revealed that many TH-positive neurons in SNc, but not in VTA, co-express MTH1, OGG1 or MUTYH. In addition, only a few microglial cells were detected in SNc, and these cells also express substantial levels of MTH1, OGG1 or MUTYH. On the other hand, astroglial cells abundantly populated in substantia nigra pars reticulata but not in SNc, and these cells express very low levels of MTH1, OGG1 or MUTYH. These results strongly suggest that these defense enzymes contribute to the maintenance of genomic integrity in dopaminergic neurons and microglia in the substantia nigra. Research fund: KAKENHI 22221004,Global COE Program. doi:10.1016/j.neures.2011.07.814 P2-r01 Effect of serotonergic drugs on motor function in a hemiparkinsonian rat model Masatoshi Inden 1,2 , Kazuyuki Takata 2, Takashi Taniguchi 2, Yoshihisa Kitamura 2 1 Clin. Pharmacol. Lab., College of Pharm. Sci., Ritsumeikan Univ., Kusatsu, Japan 2 Dept. Neurobiol., Kyoto Pharm. Univ., Kyoto, Japan Parkinson’s disease (PD) is an age-related neurodegenerative disease that is characterized by relatively selective nigrostriatal dopamine (DA) neurodegeneration. l-Dihydroxyphenylalanine (l-DOPA) is considered the gold standard for the treatment of PD. However, long-term administration of l-DOPA can induce abnormal side effects. On the other hand, selective serotonin reuptake inhibitors (SSRIs) have gained tremendous popularity in the treatment of depression in PD. SSRIs are thought to influence motor function in PD via pharmacological modification of interactions between serotonergic and dopaminergic neural networks, which are complex and not yet fully understand. In this study, rats received a unilateral intranigral injection of either 6-hydroxydopamine (6-OHDA) or vehicle. In addition, they further received a bilateral intraventricular injection of either 5,7-dihydroxytryptamine (5,7-DHT) or vehicle. In 6-OHDA-lesioned rats, lDOPA-induced rotational behavior was significantly decreased when these rats further received a bilateral intraventricular injection of 5,7-DHT. We also demonstrated that pre-treatment with fluoxetine, significantly suppressed l-DOPA-induced ERK1/2 and histone H3 phosphorylation, as well as l-DOPA-induced rotational behavior in 6-OHDA-lesioned rats. These data indicate that l-DOPA-derived DA, released as a false transmitter from 5HT terminals, enhances levels of phosphorylated ERK and histone H3, and this results in abnormal behavior. Fluoxetine may attenuate these effects of a false transmitter via 5-HT receptor. In further support of this supposition, these effects of fluoxetine were abolished by pre-treatment with WAY 100135, a 5-HT1A antagonist. These results suggest that fluoxetine may influence motor function in PD via pharmacological modification of interactions between serotonergic and dopaminergic neuronal networks. doi:10.1016/j.neures.2011.07.815 P2-r02 Intrastriatal injection of 6-hydroxydopamine induces impairments of spatial memory and causes excessive expression of ezrin in hippocampus in mice Yosuke Matsumoto 1 , Hiroki Murakami 1, Naoki Hattori 2, Kanji Yoshimoto 3, Shinji Asano 1, Masatoshi Inden 2 1 Mol. Physiol. Lab., Col. of Pharm. Sci., Ritsumeikan Univ., Kusatsu, Japan 2 Clin. Pharmacol. Lab., Col. of Pharm. Sci., Ritsumeikan Univ., Kusatsu, Japan 3 Dept. Legal. Med., Kyoto Pref. Univ. Med., Kyoto, Japan It is widely recognized that motor symptoms are accompanied by cognitive deficits in Parkinson’s disease (PD) patients even at the early stages of the disease. Dopamine (DA) lesions, obtained through dorsal striatum 6-hyroxydopamine (6-OHDA) administrations, have been found to impair memory in the spatial version of the Morris water maze in rodents of PD model. Ezrin, radixin, and moesin are collectively known as ERM proteins. Although ERM proteins have important implications in cell-shape determination and relevant signaling pathway, they have not been studied in the hippocampus in association with visuo-spatial memory impairments. The purpose of the present study is to examine whether the expression level of ERM proteins in the hippocampus is changed by an intrastriatal injection of 6-OHDA in mice. At 6 or 18 weeks after a microinjection of 6OHDA, we performed a water maze testing to examine the function of a visuo-spatial memory. The intrastriatal injection of 6-OHDA induced spatial memory impairments. After the water maze testing, we performed biochemical analyses to examine DA neurodegeneration. The microinjection of 6-OHDA reduced the striatal DA content by approximately 70%. We also performed western blotting of ERM proteins to determine the changes in their expression levels in the hippocampus. The protein level of ezrin was increased approximately 2.2-fold by intrastriatal injection of 6-OHDA whereas expression levels of other ERM proteins, moesin and radixin, were unaffected by intrastriatal injection of 6-OHDA. These results suggest that excessive ezrin may influence cognitive dysfunction in the pathological condition of PD. doi:10.1016/j.neures.2011.07.816 P2-r03 Decreased anxiety-like behavior in alpha-synuclein BAC transgenic mice recapitulates early non-motor symptoms in Parkinson disease Hodaka Yamakado 1 , Yasuhiro Moriwaki 2, Nobuyuki Yamasaki 3, Junko Kurisu 4, Tsuyoshi Miyakawa 5, Kengo Uemura 1, Haruhisa Inoue 6, Ryosuke Takahashi 1 1 Dept. of Neurol., Grad. Sch. of Med., Kyoto Univ., Kyoto 2 Dept. of Pharmacol., Keio Univ., Tokyo 3 Dept. of Psychiatry, Grad. Sch. of Med., Kyoto Univ., Kyoto 4 Lab. of Dev. Neurobiol., Grad. Sch. of Biostudies, Kyoto Univ., Kyoto 5 Div. of System Med. Sci., Inst. for Comp. Med. Sci., Fujita Health Univ., Toyoake, Aichi 6 CiRA, Kyoto Univ., Kyoto Alpha-synuclein (a-syn) is the main component of Lewy bodies, a pathological hallmark of Parkinson disease (PD), and its gene mutations (PARK1) as well as multiplications (PARK4) can cause familial forms of PD. Recently, asyn gene has also been identified as a genetic risk factor for idiopathic PD by genome-wide association studies. To make a mouse model for PARK4 as well as for idiopathic PD, we generated genome-based human a-syn BAC (bacterial artificial chromosome) transgenic mice (a-syn BAC tg mice) harboring the entire human a-syn gene as well as its gene expression regulatory regions. These mice are unique in that human a-syn is overexpressed in a physiological manner, as observed in human brains, both temporally and spatially. The a-syn BAC tg mice exhibited decreased anxiety-like behaviors and the biochemical analysis of tg mice brains showed an increase in DAT and SERT expression which may be responsible for these behavioral changes. At present increasing attention is being focused on the non-motor symptoms of PD which include autonomic failure, sleep abnormalities, and mood changes that often emerge prior to motor symptoms. The behavioral changes found in our a-syn BAC tg mice may reflect the non-motor symptoms in the preclinical stage of PD. Our a-syn BAC tg mice could be used as a valuable tool to evaluate a-syn gene dosage effects in vivo and a useful model for early therapeutic interventions against non-motor symptoms in the early stages of PD. doi:10.1016/j.neures.2011.07.817

RNA-editing frequency of serotonin 2C receptor is increased by chronic alcohol exposure

s / Neuroscience Research 68S (2010) e335–e446 e421 P3-o08 Effect of running wheel on behavior and brain monoamines in mice with or without methamphetamine challenge Nobue Kitanaka 1 , Junichi Kitanaka 1, Kaname Watabe 2, Kohichi Tanaka 3, Tomohiro Tatsuta 4, Yoshio Morita 5, Nobuyoshi Nishiyama 3, Motohiko Takemura 1 1 Department of Pharmacol., Hyogo Col. Med., Nishinomiya, Japan 2 Tech. Department, Muromachi Kikai, Co., Ltd., Tokyo, Japan 3 Div. Pharmacol, Dept Pharm, Sch Pharm, Hyogo Univ Health Sci, Kobe, Japan 4 Ibogawa Hospital Furuhashikai Medical Corporation, Hyogo, Japan 5 Fac Nursing, Baika Women’s Univ, Osaka, Japan We have investigated whether preconditioning for horizontal running wheel (Fast-TracTM) activity affected behavior and brain monoamines in mice with or without methamphetamine (METH) challenge. For three consecutive days, 10-week-old male ICR mice were housed singly with or without running wheel, injected with 1.0 mg/kg METH,and put into a measurement chamber to monitor automatically in terms of horizontal locomotion and rearing activity for three hours. After measurement, brains were dissected into three regions (cerebral cortex (CC), striatum, and thalamus + hypothalamus (TH)) and analyzed monoamines and their metabolites contents by HPLC. HPLC analysis revealed there were no significant differences between mouse groups with or without running wheel except serotonin content which significantly increased in TH in the presence of running wheel. Neither horizontal locomotion nor rearing activities were affected by preconditioning of running wheel, whereas METH treatment significantly increased both activities for three hours. METH treatment significantly decreased DOPAC content in both TH and striatum and increased dopamine and serotonin in CC and TH, respectively. During preconditioning session, mice showed greater running wheel activity than food access activity, while control animals (without a running wheel) predominantly showed a food access activity compared to mice with running wheel. In another experiment, behavioral analyses during initial three hours demonstrated that METH (1 mg/kg, i.p.) significantly decreased food and drink intakes in mice regardless of the presence or absence of running wheel, although increased locomotor activity but consistent running wheel activity were observed in mice with METH challenge. These observations indicated that a running wheel might affect serotonin content in TH, although preconditioning of running wheel did not alter mouse behavior after METH challenge. doi:10.1016/j.neures.2010.07.1865 P3-o09 Increased voluntary alcohol drinking behavior is associated with the role of serotonin 2c receptors in alcohol vaporexposed C57BL/6J mice Kanji Yoshimoto 1 , Yoshihisa Watanabe 2, Masaki Tanaka 2, Hiroshi Ikegaya 1, Minoru Kimura 3 1 Department of Forensic Medicine, Kyoto Prefectural University of Medicine 2 Dept. Cell Biol, Kyoto Pref Univ. Med, Kyoto, Japan 3 Dept. of Physiol, Koto Pref Univ Med., Kyoto, Japan The present study aimed to investigate the relationship between increases of voluntary alcohol drinking behavior during withdrawal and the neural functions of 5-HT receptor subtypes. In the 4-hr time-access alcohol test and 2-bottle alcohol preference test, C57BL/6J mice exposed to alcohol vapor for 20 consecutive days showed increases in voluntary alcohol drinking behavior. The expressions of 5-HT2C mRNA in the ACC, striatum (C/P), dorsal raphe nucleus (DRN), hippocampus (HP), and lateral hypothalamus (LH) and the expression of 5-HT2A mRNA in the DRN were increased significantly in alcohol vapor-exposed mice based on quantitative RT-PCR. In alcohol-exposed mice, the contents of 5-HT and 5HIAA decreased in the DRN, but the turnover ratios of DA and/or 5HT were increased in the DRN and ACC. The consecutive alcohol vapor inhalation induced increases in basal ACC DA and 5-HT release in the primary withdrawal stage. In the final experiment, intraperitoneal administrations of the 5-HT2C antagonist, SB 242084, not the 5-HT2c agonist, m-CPP, suppressed voluntary alcohol drinking behavior dose-dependently in the primary withdrawal stage. It was suggested that an increase in the voluntary alcohol intake of alcohol exposed mice in primary withdrawal was associated with serotonergic neuroadaptation in the ACC with an increase of 5-HT2c receptors to compensate for the degenerated serotonergic neurons in the DRN with the up regulated increase of ACC 5-HT availability. doi:10.1016/j.neures.2010.07.1866 P3-o10 Effect of psychotropic drugs on behavior of mice which show abnormal expressions of neuroglycan C, a brain-specific chondroitin sulfate proteoglycan Sachiko Aono 1 , Yoshihito Tokita 1, Fumiko Matsui 1, Atsuhiko Oohira 2, Eiji Watanabe 3 1 Departments of Perinatology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Japan 2 Research Complex of Medical Frontiers, Aichi Medical University, Aichi, Japan 3 Laboratory of Neurophysiology, National Institute for Basic Biology, Okazaki, Japan Neuroglycan C (NGC), a transmembrane chondroitin sulfate proteoglycan that is predominantly expressed in the brain, is a typical part-time proteoglycan that changes its structure from a proteoglycan form to a nonproteoglycan form without chondroitin sulfate during the development of the cerebellum and retina. To clarify the roles of NGC in development of the brain, we planned to generate NGC-gene mutant mice that show abnormal expressions of NGC by conditionally targeted disruption of the NGC gene. In the present study, we carried out experiments focusing on two strains among four we have gotten; NGC-knockout mice that are completely deficient in all splice variants and NGC-knockin mice that express NGC in non-proteoglycan form due to a mutation (S123A) at the binding site of chondroitin sulfate chain. We investigated the effect of several psychostimulants including methamphetamine on the behavior of NGC-knockout and NGCknockin mice using the open field test, because it has been reported that the behavioral sensitization to some psychotropic drugs is associated with upand downregulation of NGC gene expression. After the test, the changes of NGC mRNAs and protein patterns in the cerebral cortex and hippocampus were examined using RT-PCR and two dimensional gel electrophoresis, respectively. In this meeting, we will report the results and discuss about the significance. doi:10.1016/j.neures.2010.07.1867 P3-o11 Differential regulation of NADPH diaphorase reactive neuron in mice by acute ketamine administration Toshifumi Yamamoto 1 , Junji Yamaguchi 1, Masato Tomita 1, Hideko Yamamoto 2 1 Lab. of Mol. Psychopharmacol. Grad. School of Nanosci, Yokohama City University 2 Div. of Psychobiol., Tokyo Inst. of Psychiatry, Tokyo, Japan Ketamine (KET) is a psychotomimetic drug used to a model of schizophrenia in animals. KET is well-known as the noncompetitive antagonist for Nmethyl-D-aspartate (NMDA) receptor. Furthermore, there are several clinical and genetic evidences for an involvement of nitric oxide (NO) in schizophrenia. We have previously shown that KET induced locomotor sensitization in mice after daily and/or weekly administrations. However, the molecular mechanism of locomotor sensitization by KET remains unknown. In the present study, we investigated the effects of KET on neuronal NO synthase (nNOS) activities by using NADPH diaphorase histochemical experiment in C57BL/6 mice. Single administration of KET to mice caused rapid increase in the number of NADPH diaphorase (NADPHd) actively neuron in striatum between 10 to 30 min, with dose-dependent manner (5–50 mg/kg, sc). In addition, the frontal cortex area also increased the number of NADPHd positive neurons. On the other hand, we found that the numbers of NADPHd positive neurons in the core and shell of nucleus accumbens (NAc) were significantly decreased. These findings that blockade of NMDA receptor by KET rapidly induced NO synthesis in the corticostriatal area but reduced NO synthesis in the limbic area may provide an explanation the easy development of behavioural sensitization by few times injection of ketamine in mice. doi:10.1016/j.neures.2010.07.1868 P3-o12 RNA-editing frequency of serotonin 2C receptor is increased by chronic alcohol exposure Yoshihisa Watanabe 1 , Kanji Yoshimoto 2, Harutsugu Tatebe 3, Minoru Kimura 4, Masaki Tanaka 1 1 Department of Cell Biol., Kyoto Pref. University Med., Kyoto, Japan 2 Department Legal Med., Kyoto Pref. University Med., Kyoto, Japan 3 Department Neurol., Kyoto Pref. University Med., Kyoto, Japan 4 Department Physiol., Kyoto Pref. University Med., Kyoto, Japan Many neurotransmitters, including -aminobutyric acid, glutamate, acetylcholine, dopamine, serotonin (5HT) and endogenous opioid peptides, have been implicated in the various types of drug abuse. Alcohol, one of these

Cellular aspects of the brain dopaminergic neurogenesis in planarians

P1-f28 Histochemical analysis of two neurogenic regions in the adult ferret brain Yasuharu Takamori1, Taketoshi Wakabayashi1, Tetsuji Mori1, Kotaro Kitaya1, Jun Kosaka2, Hisao Yamada1 1 Department Anatomy and Cell Science, Kansai Medical University, Osaka, Japan; 2 Department Cytology and Histology, Okayama Uinversity Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

An age-dependent change in serotonin innervation to the forebrain of Mecp2-null mice

ALS is a progressive disease with selective motor neuron <MN> death. The cell death of MN in ALS is supposed to be not fully consistent with apoptosis, necrosis, or autophagy. Recently, it was reported that the shift of balance between YAP Cs as prosurvival factors and activated p73 promotes apoptosis in transcriptional repression-induced atypical death <TRIAD>. In this study, G93ASOD1 Tg mice were examined to investigate for possible relationships between the mechanism of MN death in ALS and TRIAD. The levels of YAP Cs in the spinal cords of Tg mice decreased with disease progression, whereas FL-YAP, a p73 cofactor that promotes apoptosis, was preserved. Also, the ratio of phosphorylation of p73 increased in Tg mice. Our results suggest that the progressive decrease in the levels of YAP Cs and the relative increase in phosphorylated p73 are correlated with disease progression in ALS model mice.