Medicine and Health Sciences Commons^™

Expression And Localization Of Nrf2/Keap1 Signalling Pathway Genes In Mouse Preimplantation Embryos Exposed To Free Fatty Acids., Grace Dionne, Michele D. Calder, Dean H Betts, Basim Abu Rafea, Andrew J Watson

Obstetrics & Gynaecology Publications

Obese women experience greater incidence of infertility, with reproductive tracts exposing preimplantation embryos to elevated free fatty acids (FFA) such as palmitic acid (PA) and oleic acid (OA). PA treatment impairs mouse preimplantation development in vitro, while OA co-treatment rescues blastocyst development of PA treated embryos. In the present study, we investigated the effects of PA and OA treatment on NRF2/Keap1 localization, and relative antioxidant enzyme (Glutathione peroxidase; Gpx1, Catalase; Cat, Superoxide dismutase; Sod1 and γ-Glutamylcysteine ligase catalytic unit; Gclc) mRNA levels, during in vitro mouse preimplantation embryo development. Female mice were superovulated, mated, and embryos cultured in the presence …

Atrx Deletion In Neurons Leads To Sexually Dimorphic Dysregulation Of Mir-137 And Spatial Learning And Memory Deficits., Renee J. Tamming, Vanessa Dumeaux, Yan Jiang, Sarfraz Shafiq, Luana Langlois, Jacob Ellegood, Lily R. Qiu, Jason P. Lerch, Nathalie G. Bérubé

Paediatrics Publications

ATRX gene mutations have been identified in syndromic and non-syndromic intellectual disabilities in humans. ATRX is known to maintain genomic stability in neuroprogenitor cells, but its function in differentiated neurons and memory processes remains largely unresolved. Here, we show that the deletion of neuronal Atrx in mice leads to distinct hippocampal structural defects, fewer presynaptic vesicles, and an enlarged postsynaptic area at CA1 apical dendrite-axon junctions. We identify male-specific impairments in long-term contextual memory and in synaptic gene expression, linked to altered miR-137 levels. We show that ATRX directly binds to the miR-137 locus and that the enrichment of the …

Effects Of A Postnatal Atrx Conditional Knockout In Neurons On Autism-Like Behaviours In Male And Female Mice., Nicole Martin-Kenny, Nathalie G Bérubé

Paediatrics Publications

BACKGROUND: Alpha-thalassemia/mental retardation, X-linked, or ATRX, is an autism susceptibility gene that encodes a chromatin remodeler. Mutations of ATRX result in the ATR-X intellectual disability syndrome and have been identified in autism spectrum disorder (ASD) patients. The mechanisms by which ATRX mutations lead to autism and autistic-like behaviours are not yet known. To address this question, we generated mice with postnatal Atrx inactivation in excitatory neurons of the forebrain and performed a battery of behavioural assays that assess autistic-like behaviours.

METHODS: Male and female mice with a postnatal conditional ablation of ATRX were generated using the Cre/lox system under the …

Evidence Of Increased Hypoxia Signaling In Fetal Liver From Maternal Nutrient Restriction In Mice., Bethany N Radford, Victor K M Han

Paediatrics Publications

BACKGROUND: Intrauterine growth restriction (IUGR) is a pregnancy condition where fetal growth is reduced, and offspring from IUGR pregnancies are at increased risk for type II diabetes as adults. The liver is susceptible to fetal undernutrition experienced by IUGR infants and animal models of growth restriction. This study aimed to examine hepatic expression changes in a maternal nutrient restriction (MNR) mouse model of IUGR to understand fetal adaptations that influence adult metabolism.

METHODS: Liver samples of male offspring from MNR (70% of ad libitum starting at E6.5) or control pregnancies were obtained at E18.5 and differential expression was assessed by …

Insights Image For "Evidence Of Increased Hypoxia Signalling In Fetal Liver From Maternal Nutrient Restriction In Mice"., Bethany N Radford, Victor K M Han

Paediatrics Publications

No abstract provided.

What We Can Learn From A Genetic Rodent Model About Autism., Dorit Möhrle, Marta Fernández, Olga Peñagarikano, Andreas Frick, Brian Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders that are caused by genetic and/or environmental impacts, often probably by the interaction of both. They are characterised by deficits in social communication and interaction and by restricted and repetitive behaviours and interests from early childhood on, causing significant impairment. While it is clear that no animal model captures the full complexity of ASD in humans, genetic models are extremely useful for studying specific symptoms associated with ASD and the underlying cellular and molecular mechanisms. In this review we summarize the behavioral paradigms used in rodents to model ASD symptoms as they …

Striatal Acetylcholine Helps To Preserve Functional Outcomes In A Mouse Model Of Stroke, Daniela F. Goncalves, Monica S. Guzman, Robert Gros, André R. Massensini, Robert Bartha, Vania F. Prado, Marco A.M. Prado

Medical Biophysics Publications

Acetylcholine (ACh) has been suggested to facilitate plasticity and improve functional recovery after different types of brain lesions. Interestingly, numerous studies have shown that striatal cholinergic interneurons are relatively resistant to acute ischemic insults, but whether ACh released by these neurons enhances functional recovery after stroke is unknown. We investigated the role of endogenous striatal ACh in stroke lesion volume and functional outcomes following middle cerebral artery occlusion to induce focal ischemia in striatum-selective vesicular acetylcholine transporter-deficient mice (stVAChT-KO). As transporter expression is almost completely eliminated in the striatum of stVAChT-KO mice, ACh release is nearly abolished in this area. …

Ctcf Governs The Identity And Migration Of Mge-Derived Cortical Interneurons., Adrienne Elbert, Daniel Vogt, Ashley Watson, Michael Levy, Yan Jiang, Emilie Brûlé, Megan E Rowland, John Rubenstein, Nathalie G Bérubé

Paediatrics Publications

The CCCTC-binding factor (CTCF) is a central regulator of chromatin topology recently linked to neurodevelopmental disorders such as intellectual disability, autism, and schizophrenia. The aim of this study was to identify novel roles of CTCF in the developing mouse brain. We provide evidence that CTCF is required for the expression of the LIM homeodomain factor LHX6 involved in fate determination of cortical interneurons (CINs) that originate in the medial ganglionic eminence (MGE). Conditional

The Loss Of Atrx Increases Susceptibility To Pancreatic Injury And Oncogenic Kras In Female But Not Male Mice., Claire C Young, Ryan M Baker, Christopher J Howlett, Todd Hryciw, Joshua E Herman, Douglas Higgs, Richard Gibbons, Howard Crawford, Arthur Brown, Christopher L Pin

Paediatrics Publications

Background

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America, accounting for >30,000 deaths annually. Although somatic activating mutations in KRAS appear in 97% of PDAC patients, additional factors are required to initiate PDAC. Because mutations in genes encoding chromatin remodelling proteins have been implicated in KRAS-mediated PDAC, we investigated whether loss of chromatin remodeler ɑ-thalassemia, mental-retardation, X-linked (ATRX) affects oncogenic KRAS’s ability to promote PDAC. ATRX affects DNA replication, repair, and gene expression and is implicated in other cancers including glioblastomas and pancreatic neuroendocrine tumors. The hypothesis was that deletion of Atrx …

Mutations In Keops-Complex Genes Cause Nephrotic Syndrome With Primary Microcephaly, Daniela A Braun, Jia Rao, Geraldine Mollet, David Schapiro, Marie-Claire Daugeron, Weizhen Tan, Olivier Gribouval, Olivia Boyer, Patrick Revy, Tilman Jobst-Schwan, Johanna Magdalena Schmidt, Jennifer A Lawson, Denny Schanze, Shazia Ashraf, Jeremy F P Ullmann, Charlotte A Hoogstraten, Nathalie Boddaert, Bruno Collinet, Gaëlle Martin, Dominique Liger, Svjetlana Lovric, Monica Furlano, I Chiara Guerrera, Oraly Sanchez-Ferras, Jennifer F Hu, Anne-Claire Boschat, Sylvia Sanquer, Björn Menten, Sarah Vergult, Nina De Rocker, Merlin Airik, Tobias Hermle, Shirlee Shril, Eugen Widmeier, Heon Yung Gee, Won-Il Choi, Carolin E Sadowski, Werner L Pabst, Jillian K Warejko, Ankana Daga, Tamara Basta, Verena Matejas, Karin Scharmann, Sandra D Kienast, Babak Behnam, Brendan Beeson, Amber Begtrup, Malcolm Bruce, Gaik-Siew Ch'ng, Shuan-Pei Lin, Jui-Hsing Chang, Chao-Huei Chen, Megan T Cho, Patrick M Gaffney, Patrick E Gipson, Chyong-Hsin Hsu, Jameela A Kari, Yu-Yuan Ke, Cathy Kiraly-Borri, Wai-Ming Lai, Emmanuelle Lemyre, Rebecca Okashah Littlejohn, Amira Masri, Mastaneh Moghtaderi, Kazuyuki Nakamura, Fatih Ozaltin, Marleen Praet, Chitra Prasad, Agnieszka Prytula, Elizabeth R Roeder, Patrick Rump, Rhonda E Schnur, Takashi Shiihara, Manish D Sinha, Neveen A Soliman, Kenza Soulami, David A Sweetser, Wen-Hui Tsai, Jeng-Daw Tsai, Rezan Topaloglu, Udo Vester, David H Viskochil, Nithiwat Vatanavicharn, Jessica L Waxler, Klaas J Wierenga, Matthias T F Wolf, Sik-Nin Wong, Sebastian A Leidel, Gessica Truglio, Peter C Dedon, Annapurna Poduri, Shrikant Mane, Richard P Lifton, Maxime Bouchard, Peter Kannu, David Chitayat, Daniella Magen, Bert Callewaert, Herman Van Tilbeurgh, Martin Zenker, Corinne Antignac, Friedhelm Hildebrandt

Paediatrics Publications

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced …

Activating Transcription Factor 3 Promotes Loss Of The Acinar Cell Phenotype In Response To Cerulein-Induced Pancreatitis In Mice, Elena N Fazio, Claire C Young, Jelena Toma, Michael Levy, Kurt R Berger, Charis L Johnson, Rashid Mehmood, Patrick Swan, Alphonse Chu, Sean P Cregan, F Jeffrey Dilworth, Christopher J Howlett, Christopher L Pin

Paediatrics Publications

Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). Although down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of >30% of differentially expressed genes during the initiation of pancreatitis. …

Mosaic Expression Of Atrx In The Mouse Central Nervous System Causes Memory Deficits, Renee J Tamming, Jennifer R Siu, Yan Jiang, Marco A M Prado, Frank Beier, Nathalie G Bérubé

Paediatrics Publications

The rapid modulation of chromatin organization is thought to play a crucial role in cognitive processes such as memory consolidation. This is supported in part by the dysregulation of many chromatin-remodelling proteins in neurodevelopmental and psychiatric disorders. A key example is ATRX, an X-linked gene commonly mutated in individuals with syndromic and nonsyndromic intellectual disability. The consequences of Atrx inactivation for learning and memory have been difficult to evaluate because of the early lethality of hemizygous-null animals. In this study, we evaluated the outcome of brain-specific Atrx deletion in heterozygous female mice. These mice exhibit a mosaic pattern of ATRX …

Oxytocin’S Effects On Sickness Behaviours, Anxiety Responses, And Immune Function In Adult Male Mice, Julie Deleemans

Electronic Thesis and Dissertation Repository

The nonapeptide, oxytocin (OT), is implicated in a range of behavioural and physiological functions. However, OT's role in sickness behaviours remains unclear. This thesis examined effects of the OT agonist, carbetocin (CBT), and OT antagonist, L-368,899, on anxiety and locomotor sickness-related behaviours and pro-inflammatory cytokines, TNF-a and IL-6, in adult male CD-1 mice. Animals received 2 intraperitoneal treatment injections. The first treatment was carbetocin, L-368,899, or saline, while the second was lipopolysaccharide (LPS) or saline. Behaviours were evaluated via the light-dark test, and cytokines via immunoassay. OT antagonist treatment attenuated LPS induced perturbations in locomotor and anxiety-like behaviour, but …

Global Deletion Of Panx3 Produces Multiple Phenotypic Effects In Mouse Humeri And Femora, Deidre Caskenette, Silvia Penuela, Vanessa Lee, Kevin Barr, Frank Beier, Dale W. Laird, Katherine E. Willmore

Anatomy and Cell Biology Publications

© 2016 Anatomical Society. Pannexins form single-membrane channels that allow passage of small molecules between the intracellular and extracellular compartments. Of the three pannexin family members, Pannexin3 (Panx3) is the least studied but is highly expressed in skeletal tissues and is thought to play a role in the regulation of chondrocyte and osteoblast proliferation and differentiation. The purpose of our study is to closely examine the in vivo effects of Panx3 ablation on long bone morphology using micro-computed tomography. Using Panx3 knockout (KO) and wildtype (WT) adult mice, we measured and compared aspects of phenotypic shape, bone mineral density (BMD), …

Neurogenesis-Mediated Forgetting Minimizes Proactive Interference., Jonathan R Epp, Rudy Silva Mera, Stefan Köhler, Sheena A Josselyn, Paul W Frankland

Brain and Mind Institute Researchers' Publications

Established memories may interfere with the encoding of new memories, particularly when existing and new memories overlap in content. By manipulating levels of hippocampal neurogenesis, here we show that neurogenesis regulates this form of proactive interference. Increasing hippocampal neurogenesis weakens existing memories and, in doing so, facilitates the encoding of new, conflicting (but not non-conflicting) information in mice. Conversely, decreasing neurogenesis stabilizes existing memories, and impedes the encoding of new, conflicting information. These results suggest that reduced proactive interference is an adaptive benefit of neurogenesis-induced forgetting.

Deletion Of Panx3 Prevents The Development Of Surgically Induced Osteoarthritis, Paxton M. Moon, Silvia Penuela, Kevin Barr, Sami Khan, Christopher L. Pin, Ian Welch, Mukundan Attur, Steven B. Abramson, Dale W. Laird, Frank Beier

Anatomy and Cell Biology Publications

© 2015, Springer-Verlag Berlin Heidelberg. Abstract: Osteoarthritis (OA) is a highly prevalent, disabling joint disease with no existing therapies to slow or halt its progression. Cartilage degeneration hallmarks OA pathogenesis, and pannexin 3 (Panx3), a member of a novel family of channel proteins, is upregulated during this process. The function of Panx3 remains poorly understood, but we consistently observed a strong increase in Panx3 immunostaining in OA lesions in both mice and humans. Here, we developed and characterized the first global and conditional Panx3 knockout mice to investigate the role of Panx3 in OA. Interestingly, global Panx3 deletion produced no …

Simulated Diabetic Ketoacidosis Therapy In Vitro Elicits Brain Cell Swelling Via Sodium-Hydrogen Exchange And Anion Transport., Keeley L Rose, Andrew J Watson, Thomas A Drysdale, Gediminas Cepinskas, Melissa Chan, C Anthony Rupar, Douglas D Fraser

Obstetrics & Gynaecology Publications

A common complication of type 1 diabetes mellitus is diabetic ketoacidosis (DKA), a state of severe insulin deficiency. A potentially harmful consequence of DKA therapy in children is cerebral edema (DKA-CE); however, the mechanisms of therapy-induced DKA-CE are unknown. Our aims were to identify the DKA treatment factors and membrane mechanisms that might contribute specifically to brain cell swelling. To this end, DKA was induced in juvenile mice with the administration of the pancreatic toxins streptozocin and alloxan. Brain slices were prepared and exposed to DKA-like conditions in vitro. Cell volume changes were imaged in response to simulated DKA therapy. …

Genomic Copy Number Variation In Mus Musculus., M Elizabeth O Locke, Maja Milojevic, Susan T Eitutis, Nisha Patel, Andrea E Wishart, Mark Daley, Kathleen A. Hill

Brain and Mind Institute Researchers' Publications

BACKGROUND: Copy number variation is an important dimension of genetic diversity and has implications in development and disease. As an important model organism, the mouse is a prime candidate for copy number variant (CNV) characterization, but this has yet to be completed for a large sample size. Here we report CNV analysis of publicly available, high-density microarray data files for 351 mouse tail samples, including 290 mice that had not been characterized for CNVs previously.

RESULTS: We found 9634 putative autosomal CNVs across the samples affecting 6.87% of the mouse reference genome. We find significant differences in the degree of …

Long Non-Coding Rna Malat1 Regulates Hyperglycaemia Induced Inflammatory Process In The Endothelial Cells., Prasanth Puthanveetil, Shali Chen, Biao Feng, Anirudh Gautam, Subrata Chakrabarti

Pathology Publications

To examine whether the long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is altered in the endothelial cells in response to glucose and the significance of such alteration. We incubated human umbilical vein endothelial cells with media containing various glucose levels. We found an increase in MALAT1 expression peaking after 12 hrs of incubation in high glucose. This increase was associated with parallel increase in serum amyloid antigen 3 (SAA3), an inflammatory ligand and target of MALAT1 and was further accompanied by increase in mRNAs and proteins of inflammatory mediators, tumour necrosis factor alpha (TNF-α) and interleukin …

Prolonged In Vivo Retention Of A Cathepsin D Targeted Optical Contrast Agent In A Mouse Model Of Alzheimer's Disease., Jonatan A Snir, Mojmir Suchy, Keith St Lawrence, Robert H E Hudson, Stephen H Pasternak, Robert Bartha

Brain and Mind Institute Researchers' Publications

BACKGROUND: Cathepsin D (CatD) is a lysosomal protease that is elevated early in Alzheimer's disease (AD). We have previously developed a Targeted contrast agent (CA) to detect CatD activity in vivo, consisting of a magnetic resonance imaging/fluorescent moiety linked to a cell penetrating peptide (CPP) by means of a CatD cleavage site and have demonstrated its uptake in the brain of an AD mouse model.

OBJECTIVE: The purpose of this study was to characterize the in vivo retention of a near infra-red fluorescent dye labeled version of this CA.

METHODS: Six adult C57Bl/6 wild-type mice and six adult 5XFAD transgenic …

The Development Of A Digital X-Ray Imaging System For The Characterization Of Transmission Of Whole-Body Vibration In Mice, Zhengyi Hu

Electronic Thesis and Dissertation Repository

Mechanical stimulus such as whole-body vibration (WBV) has shown to promote bone formation both in humans and animals. WBV has been hypothesized as a potentially useful osteoporosis intervention. While the transmission of WBV has been well characterized in humans, there is currently a lack of knowledge in the transmission of vibration in small animal models, such as mice, due to the lack of an implantable accelerometer appropriate to make such measurements. This thesis introduces an imaging-based method to quantify transmission of vibration in mice using x-ray imaging. Specifically, it utilizes motion blur of fiducial markers, which are implanted into the …

Implantation Failure In Female Kiss1-/- Mice Is Independent Of Their Hypogonadic State And Can Be Partially Rescued By Leukemia Inhibitory Factor., Michele Calder, Yee-Ming Chan, Renju Raj, Macarena Pampillo, Adrienne Elbert, Michelle Noonan, Carolina Gillio-Meina, Claudia Caligioni, Nathalie G Bérubé, Moshmi Bhattacharya, Andrew J Watson, Stephanie B Seminara, Andy V Babwah

Obstetrics & Gynaecology Publications

The hypothalamic kisspeptin signaling system is a major positive regulator of the reproductive neuroendocrine axis, and loss of Kiss1 in the mouse results in infertility, a condition generally attributed to its hypogonadotropic hypogonadism. We demonstrate that in Kiss1(-/-) female mice, acute replacement of gonadotropins and estradiol restores ovulation, mating, and fertilization; however, these mice are still unable to achieve pregnancy because embryos fail to implant. Progesterone treatment did not overcome this defect. Kiss1(+/-) embryos transferred to a wild-type female mouse can successfully implant, demonstrating the defect is due to maternal factors. Kisspeptin and its receptor are expressed in the mouse …

Analysis Of Neonatal Brain Lacking Atrx Or Mecp2 Reveals Changes In Nucleosome Density, Ctcf Binding And Chromatin Looping, Kristin D Kernohan, Douglas Vernimmen, Gregory B Gloor, Nathalie G. Bérubé

Paediatrics Publications

ATRX and MeCP2 belong to an expanding group of chromatin-associated proteins implicated in human neurodevelopmental disorders, although their gene-regulatory activities are not fully resolved. Loss of ATRX prevents full repression of an imprinted gene network in the postnatal brain and in this study we address the mechanistic aspects of this regulation. We show that ATRX binds many imprinted domains individually but that transient co-localization between imprinted domains in the nuclei of neurons does not require ATRX. We demonstrate that MeCP2 is required for ATRX recruitment and that deficiency of either ATRX or MeCP2 causes decreased frequency of long-range chromatin interactions …

Characterization Of A Far-Red Analog Of Ghrelin For Imaging Ghs-R In P19-Derived Cardiomyocytes., Gregory A F Douglas, Rebecca Mcgirr, Carlie L Charlton, Dov B Kagan, Lisa M Hoffman, Leonard G Luyt, Savita Dhanvantari

Medical Biophysics Publications

Ghrelin and its receptor, the growth hormone secretagogue receptor (GHS-R), are expressed in the heart, and may function to promote cardiomyocyte survival, differentiation and contractility. Previously, we had generated a truncated analog of ghrelin conjugated to fluorescein isothiocyanate for the purposes of determining GHS-R expression in situ. We now report the generation and characterization of a far-red ghrelin analog, [Dpr(3)(octanoyl), Lys(19)(Cy5)]ghrelin (1-19), and show that it can be used to image changes in GHS-R in developing cardiomyocytes. We also generated the des-acyl analog, des-acyl [Lys(19)(Cy5)]ghrelin (1-19) and characterized its binding to mouse heart sections. Receptor binding affinity of Cy5-ghrelin as …

The Touchscreen Operant Platform For Assessing Executive Function In Rats And Mice., Adam C Mar, Alexa E Horner, Simon R O Nilsson, Johan Alsiö, Brianne A Kent, Chi Hun Kim, Andrew Holmes, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

This protocol details a subset of assays developed within the touchscreen platform to measure various aspects of executive function in rodents. Three main procedures are included: extinction, measuring the rate and extent of curtailing a response that was previously, but is no longer, associated with reward; reversal learning, measuring the rate and extent of switching a response toward a visual stimulus that was previously not, but has become, associated with reward (and away from a visual stimulus that was previously, but is no longer, rewarded); and the 5-choice serial reaction time (5-CSRT) task, gauging the ability to selectively detect and …

The Touchscreen Operant Platform For Testing Working Memory And Pattern Separation In Rats And Mice., Charlotte A Oomen, Martha Hvoslef-Eide, Christopher J Heath, Adam C Mar, Alexa E Horner, Timothy J Bussey, Lisa M Saksida

Brain and Mind Institute Researchers' Publications

The automated touchscreen operant chamber for rats and mice allows for the assessment of multiple cognitive domains within the same testing environment. This protocol presents the location discrimination (LD) task and the trial-unique delayed nonmatching-to-location (TUNL) task, which both assess memory for location. During these tasks, animals are trained to a predefined criterion during ∼20-40 daily sessions. In LD sessions, touching the same location on the screen is rewarded on consecutive trials, followed by a reversal of location-reward contingencies. TUNL, a working memory task, requires animals to 'nonmatch' to a sample location after a delay. In both the LD and …

The Touchscreen Operant Platform For Testing Learning And Memory In Rats And Mice., Alexa E Horner, Christopher J Heath, Martha Hvoslef-Eide, Brianne A Kent, Chi Hun Kim, Simon R O Nilsson, Johan Alsiö, Charlotte A Oomen, Andrew Holmes, Lisa M Saksida, Timothy J Bussey

Brain and Mind Institute Researchers' Publications

An increasingly popular method of assessing cognitive functions in rodents is the automated touchscreen platform, on which a number of different cognitive tests can be run in a manner very similar to touchscreen methods currently used to test human subjects. This methodology is low stress (using appetitive rather than aversive reinforcement), has high translational potential and lends itself to a high degree of standardization and throughput. Applications include the study of cognition in rodent models of psychiatric and neurodegenerative diseases (e.g., Alzheimer's disease, schizophrenia, Huntington's disease, frontotemporal dementia), as well as the characterization of the role of select brain regions, …

Stress-Inducible Phosphoprotein 1 Has Unique Cochaperone Activity During Development And Regulates Cellular Response To Ischemia Via The Prion Protein., Flavio H Beraldo, Iaci N Soares, Daniela F Goncalves, Jue Fan, Anu A Thomas, Tiago G Santos, Amro H Mohammad, Martin Roffé, Michele D Calder, Simona Nikolova, Glaucia N Hajj, Andre L Guimaraes, Andre R Massensini, Ian Welch, Dean H Betts, Robert Gros, Maria Drangova, Andrew J Watson, Robert Bartha, Vania F Prado, Vilma R Martins, Marco A M Prado

Obstetrics & Gynaecology Publications

Stress-inducible phosphoprotein 1 (STI1) is part of the chaperone machinery, but it also functions as an extracellular ligand for the prion protein. However, the physiological relevance of these STI1 activities in vivo is unknown. Here, we show that in the absence of embryonic STI1, several Hsp90 client proteins are decreased by 50%, although Hsp90 levels are unaffected. Mutant STI1 mice showed increased caspase-3 activation and 50% impairment in cellular proliferation. Moreover, placental disruption and lack of cellular viability were linked to embryonic death by E10.5 in STI1-mutant mice. Rescue of embryonic lethality in these mutants, by transgenic expression of the …

P38 Mapk Regulates Cavitation And Tight Junction Function In The Mouse Blastocyst., Christine E Bell, Andrew J Watson

Obstetrics & Gynaecology Publications

UNLABELLED: Blastocyst formation is essential for implantation and maintenance of pregnancy and is dependent on the expression and coordinated function of a series of proteins involved in establishing and maintaining the trans-trophectoderm ion gradient that enables blastocyst expansion. These consist of Na/K-ATPase, adherens junctions, tight junctions (TJ) and aquaporins (AQP). While their role in supporting blastocyst formation is established, the intracellular signaling pathways that coordinate their function is unclear. The p38 MAPK pathway plays a role in regulating these proteins in other cell types and is required for embryo development at the 8-16 cell stage, but its role has not …

Mice With Deficient Bk Channel Function Show Impaired Prepulse Inhibition And Spatial Learning, But Normal Working And Spatial Reference Memory., Marei Typlt, Magdalena Mirkowski, Erin Azzopardi, Lukas Ruettiger, Peter Ruth, Susanne Schmid

Brain and Mind Institute Researchers' Publications

Genetic variations in the large-conductance, voltage- and calcium activated potassium channels (BK channels) have been recently implicated in mental retardation, autism and schizophrenia which all come along with severe cognitive impairments. In the present study we investigate the effects of functional BK channel deletion on cognition using a genetic mouse model with a knock-out of the gene for the pore forming α-subunit of the channel. We tested the F1 generation of a hybrid SV129/C57BL6 mouse line in which the slo1 gene was deleted in both parent strains. We first evaluated hearing and motor function to establish the suitability of this …