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Transcriptomics and proteomics analyses of the PACAP38 influenced ischemic brain in permanent middle cerebral artery occlusion model mice
Hori Motohide,Nakamachi Tomoya,Rakwal Randeep,Shibato Junko
Journal of Neuroinflammation , 2012, DOI: 10.1186/1742-2094-9-256
Abstract: Introduction The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is considered to be a potential therapeutic agent for prevention of cerebral ischemia. Ischemia is a most common cause of death after heart attack and cancer causing major negative social and economic consequences. This study was designed to investigate the effect of PACAP38 injection intracerebroventrically in a mouse model of permanent middle cerebral artery occlusion (PMCAO) along with corresponding SHAM control that used 0.9% saline injection. Methods Ischemic and non-ischemic brain tissues were sampled at 6 and 24 hours post-treatment. Following behavioral analyses to confirm whether the ischemia has occurred, we investigated the genome-wide changes in gene and protein expression using DNA microarray chip (4x44K, Agilent) and two-dimensional gel electrophoresis (2-DGE) coupled with matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS), respectively. Western blotting and immunofluorescent staining were also used to further examine the identified protein factor. Results Our results revealed numerous changes in the transcriptome of ischemic hemisphere (ipsilateral) treated with PACAP38 compared to the saline-injected SHAM control hemisphere (contralateral). Previously known (such as the interleukin family) and novel (Gabra6, Crtam) genes were identified under PACAP influence. In parallel, 2-DGE analysis revealed a highly expressed protein spot in the ischemic hemisphere that was identified as dihydropyrimidinase-related protein 2 (DPYL2). The DPYL2, also known as Crmp2, is a marker for the axonal growth and nerve development. Interestingly, PACAP treatment slightly increased its abundance (by 2-DGE and immunostaining) at 6 h but not at 24 h in the ischemic hemisphere, suggesting PACAP activates neuronal defense mechanism early on. Conclusions This study provides a detailed inventory of PACAP influenced gene expressions and protein targets in mice ischemic brain, and suggests new targets for thereaupetic interventions.
Correction: Transcriptomics and proteomics analyses of the PACAP38 influenced ischemic brain in permanent middle cerebral artery occlusion model mice
Hori Motohide,Nakamachi Tomoya,Rakwal Randeep,Shibato Junko
Journal of Neuroinflammation , 2013, DOI: 10.1186/1742-2094-10-18
Unraveling the Specific Ischemic Core and Penumbra Transcriptome in the Permanent Middle Cerebral Artery Occlusion Mouse Model Brain Treated with the Neuropeptide PACAP38
Motohide Hori,Tomoya Nakamachi,Junko Shibato,Randeep Rakwal,Seiji Shioda,Satoshi Numazawa
Microarrays , 2015, DOI: 10.3390/microarrays4010002
Abstract: Our group has been systematically investigating the effects of the neuropeptide pituitary adenylate-cyclase activating polypeptide (PACAP) on the ischemic brain. To do so, we have established and utilized the permanent middle cerebral artery occlusion (PMCAO) mouse model, in which PACAP38 (1 pmol) injection is given intracerebroventrically and?compared to a control saline (0.9% sodium chloride, NaCl) injection, to unravel genome?wide gene expression changes using a high-throughput DNA microarray analysis approach. In our previous studies, we have accumulated a large volume of data (gene inventory) from the whole brain (ipsilateral and contralateral hemispheres) after both PMCAO and post-PACAP38 injection. In our latest research, we have targeted specifically infarct or ischemic core (hereafter abbreviated IC) and penumbra (hereafter abbreviated P) post-PACAP38 injections in order to re-examine the transcriptome at 6 and 24 h post injection. The current study aims to delineate the specificity of expression and localization of differentially expressed molecular factors influenced by PACAP38 in the IC and P regions. Utilizing the mouse 4 × 44 K whole genome DNA chip we show numerous changes (≧/≦ 1.5/0.75-fold) at both 6 h (654 and 456, and 522 and 449 up- and down-regulated genes for IC and P, respectively) and 24 h (2568 and 2684, and 1947 and 1592 up- and down-regulated genes for IC and P, respectively) after PACAP38 treatment. Among the gene inventories obtained here, two genes, brain-derived neurotrophic factor ( Bdnf) and transthyretin ( Ttr) were found to be induced by PACAP38 treatment, which we had not been able to identify previously using the whole hemisphere transcriptome analysis. Using bioinformatics analysis by pathway- or specific-disease-state focused gene classifications and Ingenuity Pathway Analysis (IPA) the differentially expressed genes are functionally classified and discussed. Among these, we specifically discuss some novel and previously identified genes, such as alpha hemoglobin stabilizing protein ( Ahsp), cathelicidin antimicrobial peptide ( Camp), chemokines, interferon beta 1 ( Ifnb1), and interleukin 6 ( Il6) in context of PACAP38-mediated neuroprotection in the ischemic brain. Taken together, the DNA microarray analysis provides not only a great resource for further study, but also reinforces the importance of region-specific analyses in genome-wide identification of target molecular factors that might play a role in the neuroprotective function of PACAP38.
Limit of the Principal’s Information  [PDF]
Kazumi Hori
Theoretical Economics Letters (TEL) , 2017, DOI: 10.4236/tel.2017.72018
Abstract: This note characterizes the optimal contract when a principal has unverifiable subjective information that is correlated with an agent’s private information. We find that the principal’s subjective information cannot alleviate the information asymmetry and, moreover, the second best contract is independent from it if the correlation is low.
Meta review of systematic and meta analytic reviews on movement differences, effect of movement based interventions, and the underlying neural mechanisms in autism spectrum disorder
Motohide Miyahara
Frontiers in Integrative Neuroscience , 2013, DOI: 10.3389/fnint.2013.00016
Abstract: Purposes: To identify and appraise evidence from published systematic and meta analytic reviews on (1) movement differences of individuals with autism spectrum disorders (ASD); (2) the effects of movement based interventions for ASD; (3) hypothesized underlying neural mechanisms for the movement characteristics.
A Bilocal Field Theory in Four Dimensions
Takayuki Hori
Physics , 1993, DOI: 10.1103/PhysRevD.48.R444
Abstract: A bilocal field theory having M\"{o}bius gauge invariance is proposed. In four dimensions there exists a zero momentum state of the first quantized model, which belongs to a non-trivial BRS cohomology class. A field theory lagrangian having a gauge invariance only in four dimensions is constructed.
Global Aspects Of Gauged Wess-Zumino-Witten Models
Kentaro Hori
Physics , 1994, DOI: 10.1007/BF02506384
Abstract: A study of the gauged Wess-Zumino-Witten models is given focusing on the effect of topologically non-trivial configurations of gauge fields. A correlation function is expressed as an integral over a moduli space of holomorphic bundles with quasi-parabolic structure. Two actions of the fundamental group of the gauge group is defined: One on the space of gauge invariant local fields and the other on the moduli spaces. Applying these in the integral expression, we obtain a certain identity which relates correlation functions for configurations of different topologies. It gives an important information on the topological sum for the partition and correlation functions.
Constraints For Topological Strings In $D\geq 1$
Kentaro Hori
Physics , 1994, DOI: 10.1016/0550-3213(95)00004-C
Abstract: New relations of correlation functions are found in topological string theory; one for each second cohomology class of the target space. They are close cousins of the Deligne-Dijkgraaf-Witten's puncture and dilaton equations. When combined with the dilaton equation and the ghost number conservation, the equation for the first chern class of the target space gives a constraint on the topological sum (over genera and (multi-)degrees) of partition functions. For the $\CP^1$ model, it coincides with the dilatation constraint which is derivable in the matrix model recently introduced by Eguchi and Yang.
Exact Solutions to the Wheeler-DeWitt Equation of Two Dimensional Dilaton Gravity
Takayuki Hori
Physics , 1993, DOI: 10.1143/PTP.90.743
Abstract: The two dimensional dilaton gravity with the cosmological term and with an even number of matter fields minimally coupled to the gravity is considered. The exact solutions to the Wheeler-DeWitt equation are obtained in an explicit functional form, which contain an arbitrary holomorphic function of the matter fields.
BRS Cohomology of a Bilocal Model
Takayuki Hori
Physics , 1995, DOI: 10.1143/PTP.95.803
Abstract: We present a model in which a gauge symmetry of a field theory is intrinsic in the geometry of an extended space time itself. A consequence is that the dimension of our space time is restricted through the BRS cohomology. If the Hilbert space is a dense subspace of the space of all square integrable $C^{\infty}$ functions, the BRS cohomology classes are nontrivial only when the dimension is two or four.
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