Open Access. Powered by Scholars. Published by Universities.®

Cell and Developmental Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Rats

Discipline
Institution
Publication Year
Publication
Publication Type
File Type

Articles 1 - 30 of 32

Full-Text Articles in Cell and Developmental Biology

Zinc Treatment Reverses And Anti-Zn-Regulated Mirs Suppress Esophageal Carcinomas In Vivo, Louise Fong, Kay Huebner, Ruiyan Jing, Karl Smalley, Christopher R Brydges, Oliver Fiehn, John Farber, Carlo M Croce May 2023

Zinc Treatment Reverses And Anti-Zn-Regulated Mirs Suppress Esophageal Carcinomas In Vivo, Louise Fong, Kay Huebner, Ruiyan Jing, Karl Smalley, Christopher R Brydges, Oliver Fiehn, John Farber, Carlo M Croce

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Esophageal squamous cell carcinoma (ESCC) is a deadly disease with few prevention or treatment options. ESCC development in humans and rodents is associated with Zn deficiency (ZD), inflammation, and overexpression of oncogenic microRNAs: miR-31 and miR-21. In a ZD-promoted ESCC rat model with upregulation of these miRs, systemic antimiR-31 suppresses the miR-31-EGLN3/STK40-NF-κB-controlled inflammatory pathway and ESCC. In this model, systemic delivery of Zn-regulated antimiR-31, followed by antimiR-21, restored expression of tumor-suppressor proteins targeted by these specific miRs: STK40/EGLN3 (miR-31), PDCD4 (miR-21), suppressing inflammation, promoting apoptosis, and inhibiting ESCC development. Moreover, ESCC-bearing Zn-deficient (ZD) rats receiving Zn medication showed a 47% …


Developmental Changes In Electrophysiological Properties Of Auditory Cortical Neurons In The Cntnap2 Knockout Rat, Rajkamalpreet S Mann, Brian L Allman, Susanne Schmid Apr 2023

Developmental Changes In Electrophysiological Properties Of Auditory Cortical Neurons In The Cntnap2 Knockout Rat, Rajkamalpreet S Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

Disruptions in the CNTNAP2 gene are known to cause language impairments and symptoms associated with autism spectrum disorder (ASD). Importantly, knocking out this gene in rodents results in ASD-like symptoms that include auditory processing deficits. This study used in vitro patch-clamp electrophysiology to examine developmental alterations in auditory cortex pyramidal neurons of Cntnap2-/- rats, hypothesizing that CNTNAP2 is essential for maintaining intrinsic neuronal properties and synaptic wiring in the developing auditory cortex. Whole cell patch-clamp recordings were conducted in wildtype and Cntnap2-/- littermates at three postnatal age ranges (P8-12, P18-21, and …


Differences In Startle And Prepulse Inhibition In Contactin-Associated Protein-Like 2 Knock-Out Rats Are Associated With Sex-Specific Alterations In Brainstem Neural Activity, Alice Zheng, Kaela E Scott, Ashley L Schormans, Rajkamalpreet Mann, Brian L Allman, Susanne Schmid Mar 2023

Differences In Startle And Prepulse Inhibition In Contactin-Associated Protein-Like 2 Knock-Out Rats Are Associated With Sex-Specific Alterations In Brainstem Neural Activity, Alice Zheng, Kaela E Scott, Ashley L Schormans, Rajkamalpreet Mann, Brian L Allman, Susanne Schmid

Anatomy and Cell Biology Publications

The contactin-associated protein-like 2 (CNTNAP2) gene encodes for the CASPR2 protein, which plays an essential role in neurodevelopment. Mutations in CNTNAP2 are associated with neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. Rats with a loss of function mutation in the Cntnap2 gene show increased acoustic startle response (ASR) and decreased prepulse inhibition (PPI). The neural basis of this altered auditory processing in Cntnap2 knock-out rats is currently unknown. Auditory brainstem recordings previously revealed no differences between the genotypes. The next step is to investigate brainstem structures outside of the primary auditory pathway that mediate ASR and PPI, which are …


Hyperexcitable And Immature-Like Neuronal Activity In The Auditory Cortex Of Adult Rats Lacking The Language-Linked Cntnap2 Gene., Kaela E Scott, Rajkamalpreet S Mann, Ashley L Schormans, Susanne Schmid, Brian L Allman Oct 2022

Hyperexcitable And Immature-Like Neuronal Activity In The Auditory Cortex Of Adult Rats Lacking The Language-Linked Cntnap2 Gene., Kaela E Scott, Rajkamalpreet S Mann, Ashley L Schormans, Susanne Schmid, Brian L Allman

Anatomy and Cell Biology Publications

The contactin-associated protein-like 2 gene, CNTNAP2, is a highly penetrant risk gene thought to play a role in the genetic etiology of language-related disorders, such as autism spectrum disorder and developmental language disorder. Despite its candidacy for influencing language development, few preclinical studies have examined the role of CNTNAP2 in auditory processing. Using in vivo and in vitro electrophysiological recordings in a rat model with translational validity, we report that a loss of the Cntnap2 gene function caused immature-like cortical evoked potentials, delayed multiunit response latencies to acoustic stimuli, impaired temporal processing, and led to a pattern of hyperexcitability in …


Long-Term Impacts Of Acute Stressor Exposure On Locus Coeruleus Function And Anxiety-Like Behavior In Rats, Olga Borodovitsyna Apr 2021

Long-Term Impacts Of Acute Stressor Exposure On Locus Coeruleus Function And Anxiety-Like Behavior In Rats, Olga Borodovitsyna

Graduate School of Biomedical Sciences Theses and Dissertations

Stress is a physiological state characterized by behavioral arousal that occurs during exposure to harmful or threatening stimuli, and usually facilitates an adaptive behavioral response. The persistence of stress sometimes causes it to become maladaptive, potentially contributing to disease development, including physiological complications with altered neuroendocrine signaling and impaired function of organ systems, and psychological conditions including depression and anxiety. Anxiety disorders in particular are associated with a history of stress and are the most common class of mental disorders, with a lifetime prevalence of 33.7% in the general population. The locus coeruleus (LC) is a major node in the …


Glioma-Derived Exosomes Drive The Differentiation Of Neural Stem Cells To Astrocytes, Krishna D. Sharma, Danielle Schaal, Rajshekhar A. Kore, Rabab N. Hamzah, Sahitya Chetan Pandanaboina, Abdallah Hayar, Robert J. Griffin, Malathi Srivatsan, Nathan S. Reyna, Jennifer Yanhua Xie Jul 2020

Glioma-Derived Exosomes Drive The Differentiation Of Neural Stem Cells To Astrocytes, Krishna D. Sharma, Danielle Schaal, Rajshekhar A. Kore, Rabab N. Hamzah, Sahitya Chetan Pandanaboina, Abdallah Hayar, Robert J. Griffin, Malathi Srivatsan, Nathan S. Reyna, Jennifer Yanhua Xie

Articles

Exosomes appear to be effective inter-cellular communicators delivering several types of molecules, such as proteins and RNAs, suggesting that they could influence neural stem cell (NSC) differentiation. Our RNA sequencing studies demonstrated that the RNAs related to cell proliferation and astrocyte differentiation were upregulated in human mesenchymal stem cells (hMSC) when co-cultured with exosomes obtained from the culture medium of human glioma cells (U87). Metallothionein 3 and elastin genes, which are related to cell proliferation, increased 10 and 7.2 fold, respectively. Expression of genes for astrocyte differentiation, such as tumor growth factor alpha, induced protein 3 of the NOTCH1 family, …


What We Can Learn From A Genetic Rodent Model About Autism., Dorit Möhrle, Marta Fernández, Olga Peñagarikano, Andreas Frick, Brian Allman, Susanne Schmid Feb 2020

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 …


Developmental Changes In The Activation And Structure Of The Contextual Fear Neural Circuit From Infancy To Adulthood, Anthony John Santarelli Jan 2019

Developmental Changes In The Activation And Structure Of The Contextual Fear Neural Circuit From Infancy To Adulthood, Anthony John Santarelli

Legacy Theses & Dissertations (2009 - 2024)

The contextual fear circuit, centered on the basolateral nucleus of the amygdala (BLA), is comprised of projections from the hippocampal formation and prefrontal cortex, and mediates an animals ability to learn and predict associations between the environment and biologically relevant stimuli. While the function and structure of this circuit has been well characterized in adult species, relatively little is known about its development as an animal transitions from infancy to adulthood. Recent evidence has begun to suggest that infants, juveniles, and adolescents may show remarkable heterogeneity in the behavioral, activational, and structural properties of the circuit. In this thesis, I …


N-Glycosylation Regulates Pannexin 2 Localization But Is Not Required For Interacting With Pannexin 1., Rafael E Sanchez-Pupo, Danielle Johnston, Silvia Penuela Jun 2018

N-Glycosylation Regulates Pannexin 2 Localization But Is Not Required For Interacting With Pannexin 1., Rafael E Sanchez-Pupo, Danielle Johnston, Silvia Penuela

Anatomy and Cell Biology Publications

Pannexins (Panx1, 2, 3) are channel-forming glycoproteins expressed in mammalian tissues. We previously reported that N-glycosylation acts as a regulator of the localization and intermixing of Panx1 and Panx3, but its effects on Panx2 are currently unknown. Panx1 and Panx2 intermixing can regulate channel properties, and both pannexins have been implicated in neuronal cell death after ischemia. Our objectives were to validate the predicted N-glycosylation site of Panx2 and to study the effects of Panx2 glycosylation on localization and its capacity to interact with Panx1. We used site-directed mutagenesis, enzymatic de-glycosylation, cell-surface biotinylation, co-immunoprecipitation, and confocal microscopy. Our results showed …


Characterization Of A Silac Method For Proteomic Analysis Of Primary Rat Microglia, Ping Zhang, Ashley E. Culver-Cochran, Stanley M. Stevens Jr., Bin Liu May 2016

Characterization Of A Silac Method For Proteomic Analysis Of Primary Rat Microglia, Ping Zhang, Ashley E. Culver-Cochran, Stanley M. Stevens Jr., Bin Liu

Molecular Biosciences Faculty Publications

Microglia play important and dynamic roles in mediating a variety of physiological and pathological processes during the development, normal function and degeneration of the central nervous system. Application of SILAC-based proteomic analysis would greatly facilitate the identification of cellular pathways regulating the multifaceted phenotypes of microglia. We and others have successfully SILAC-labeled immortalized murine microglial cell lines in previous studies. In this study, we report the development and evaluation of a SILAC-labeled primary rat microglia model. Although the isotope labeling scheme for primary microglia is drastically different from that of immortalized cell lines, our de novo and uninterrupted primary culture …


Measurement Of Elastic Modulus Of Collagen Type I Single Fiber, Pavel Dutov, Olga Antipova, Sameer Varma, Joseph P R O Orgel, Jay D Schieber Jan 2016

Measurement Of Elastic Modulus Of Collagen Type I Single Fiber, Pavel Dutov, Olga Antipova, Sameer Varma, Joseph P R O Orgel, Jay D Schieber

Molecular Biosciences Faculty Publications

Collagen fibers are the main components of the extra cellular matrix and the primary contributors to the mechanical properties of tissues. Here we report a novel approach to measure the longitudinal component of the elastic moduli of biological fibers under conditions close to those found in vivo and apply it to type I collagen from rat tail tendon. This approach combines optical tweezers, atomic force microscopy, and exploits Euler-Bernoulli elasticity theory for data analysis. This approach also avoids drying for measurements or visualization, since samples are freshly extracted. Importantly, strains are kept below 0.5%, which appear consistent with the linear …


Pharmaceutical Integrated Stress Response Enhancement Protects Oligodendrocytes And Provides A Potential Multiple Sclerosis Therapeutic., Sharon W Way, Joseph R Podojil, Benjamin L Clayton, Anita Zaremba, Tassie L Collins, Rejani B Kunjamma, Andrew P Robinson, Pedro Brugarolas, Robert H. Miller, Stephen D Miller, Brian Popko Mar 2015

Pharmaceutical Integrated Stress Response Enhancement Protects Oligodendrocytes And Provides A Potential Multiple Sclerosis Therapeutic., Sharon W Way, Joseph R Podojil, Benjamin L Clayton, Anita Zaremba, Tassie L Collins, Rejani B Kunjamma, Andrew P Robinson, Pedro Brugarolas, Robert H. Miller, Stephen D Miller, Brian Popko

Anatomy and Regenerative Biology Faculty Publications

Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-γ. In a mouse model of MS, experimental …


Majority Of Cells Lining The Walls Of The 3rd Ventricle In The Adult Rat Brain Are Not Neural Progenitor Cells, C. Hasken, S. Vermilyea, M. Hendrickson, R. Kalil Nov 2014

Majority Of Cells Lining The Walls Of The 3rd Ventricle In The Adult Rat Brain Are Not Neural Progenitor Cells, C. Hasken, S. Vermilyea, M. Hendrickson, R. Kalil

Annual Student Research Poster Session

No abstract provided.


Developmental Expression Of A Candidate Mullerian Inhibiting Substance Type Ii Receptor, Jose Teixeira, Wei He, Paresh Shah, Nobuyuki Morikawa, Mary Lee, Elizabeth Catlin, Peter Hudson, John Wing, David Maclaughlin, Patricia Donahoe Sep 2014

Developmental Expression Of A Candidate Mullerian Inhibiting Substance Type Ii Receptor, Jose Teixeira, Wei He, Paresh Shah, Nobuyuki Morikawa, Mary Lee, Elizabeth Catlin, Peter Hudson, John Wing, David Maclaughlin, Patricia Donahoe

Mary M. Lee

We have isolated a candidate Mullerian inhibiting substance (MIS) type II receptor complementary DNA from an embryonic rat urogenital ridge library and have studied its binding to MIS, its developmental pattern of expression and tissue distribution. By in situ hybridization with a full-length riboprobe, the receptor is expressed in the mesenchymal cells surrounding the Mullerian duct at embryonic days 14, 15, and 16 and in tubular and follicular structures of the rat fetal gonads. Expression of the messenger RNA was also seen in the granules cells and seminiferous tubules of pubertal gonads. Northern analysis revealed that the MIS type II …


Developmentally Regulated Polyadenylation Of Two Discrete Messenger Ribonucleic Acids For Mullerian Inhibiting Substance, Mary Lee, Richard Cate, Patricia Donahoe, Gerald Waneck Sep 2014

Developmentally Regulated Polyadenylation Of Two Discrete Messenger Ribonucleic Acids For Mullerian Inhibiting Substance, Mary Lee, Richard Cate, Patricia Donahoe, Gerald Waneck

Mary M. Lee

Mullerian inhibiting substance (MIS) is a 140-kilodalton homodimeric glycoprotein that causes regression of the Mullerian ducts in male embryos, and may also have a role in both males and females in the regulation of germ cell maturation. We examined the ontogeny of MIS messenger RNA (mRNA) in rat testes from midgestation through adulthood and found two discrete MIS mRNA species that are developmentally regulated. The larger 2.0-kilobase species is abundant at embryonic day 14, then decreases in late gestation, and is barely detectable after birth. The smaller 1.8-kilobase species is first noted at embryonic day 18 and is the major …


Mullerian-Inhibiting Substance Inhibits Rat Leydig Cell Regeneration After Ethylene Dimethanesulphonate Ablation, Antonio Salva, Matthew Hardy, Xiufeng Wu, Chantal Sottas, David Maclaughlin, Patricia Donahoe, Mary Lee Sep 2014

Mullerian-Inhibiting Substance Inhibits Rat Leydig Cell Regeneration After Ethylene Dimethanesulphonate Ablation, Antonio Salva, Matthew Hardy, Xiufeng Wu, Chantal Sottas, David Maclaughlin, Patricia Donahoe, Mary Lee

Mary M. Lee

The postnatal development of Leydig cell precursors is postulated to be controlled by Sertoli cell secreted factors, which may have a determinative influence on Leydig cell number and function in sexually mature animals. One such hormone, Mullerian inhibiting substance (MIS), has been shown to inhibit DNA synthesis and steroidogenesis in primary Leydig cells and Leydig cell tumor lines. To further delineate the effects of MIS on Leydig cell proliferation and steroidogenesis, we employed the established ethylene dimethanesulphonate (EDS) model of Leydig cell regeneration. Following EDS ablation of differentiated Leydig cells in young adult rats, recombinant MIS or vehicle was delivered …


Mullerian Inhibiting Substance Ontogeny And Its Modulation By Follicle-Stimulating Hormone In The Rat Testes, Tatsuo Kuroda, Mary Lee, Christopher Haqq, David Powell, Thomas Manganaro, Patricia Donahoe Sep 2014

Mullerian Inhibiting Substance Ontogeny And Its Modulation By Follicle-Stimulating Hormone In The Rat Testes, Tatsuo Kuroda, Mary Lee, Christopher Haqq, David Powell, Thomas Manganaro, Patricia Donahoe

Mary M. Lee

Mullerian Inhibiting Substance (MIS) production in rat testes from the late fetal to the adult period and its modulation by gonadotropins in neonatal testes were studied using immunohistochemistry, northern analysis, and a graded organ culture bioassay for MIS. The intense immunohistochemical staining for MIS seen in fetal and newborn testes began to decrease gradually after the third postnatal day, then decreased dramatically on the fifth postnatal day. MIS immunohistochemical activity was then present at a low level until about the 20th postnatal day, after which it was barely detectable. The testes from rats treated with FSH at birth showed a …


Mullerian Inhibiting Substance Inhibits Testosterone Synthesis In Adult Rats, V. Sriraman, E. Niu, J. Matias, Patricia Donahoe, David Maclaughlin, Matthew Hardy, Mary Lee Sep 2014

Mullerian Inhibiting Substance Inhibits Testosterone Synthesis In Adult Rats, V. Sriraman, E. Niu, J. Matias, Patricia Donahoe, David Maclaughlin, Matthew Hardy, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) is a gonadal hormone that causes regression of the Mullerian ducts during male sexual differentiation. Postnatally, MIS inhibits the proliferation and differentiation of immature Leydig cells, and transgenic mice that overexpress MIS have decreased serum testosterone concentrations. To elucidate the effects of MIS on androgen regulation in the postnatal testis, we examined testosterone synthesis in adult Sprague-Dawley rats following intratesticular and intraperitoneal injections of MIS. Intratesticular MIS injection achieved high local concentrations of MIS (574.0 +/- 60.0 ng/mL) at 4 hours, with a corresponding decline in serum testosterone concentrations to 0.7 +/- 0.1 ng/mL, compared to …


Androgen Profiles During Pubertal Leydig Cell Development In Mice, Xiufeng Wu, Ramamani Arumugam, Ningning Zhang, Mary Lee Sep 2014

Androgen Profiles During Pubertal Leydig Cell Development In Mice, Xiufeng Wu, Ramamani Arumugam, Ningning Zhang, Mary Lee

Mary M. Lee

Postnatal Leydig cell (LC) development in mice has been assumed empirically to resemble that of rats, which have characteristic hormonal profiles at well-defined maturational stages. To characterize the changes in LC function and gene expression in mice, we examined reproductive hormone expression from birth to 180 days, and quantified in vivo and in vitro production of androgens during sexual maturation. Although the overall plasma androgen and LH profiles from birth through puberty were comparable to that of rats, the timing of developmental changes in androgen production and steroidogenic capacity of isolated LCs differed. In mice, onset of androgen biosynthetic capacity, …


Mullerian-Inhibiting Substance Type Ii Receptor Expression And Function In Purified Rat Leydig Cells, Mary Lee, C. Seah, P. Masiakos, Chantal Sottas, F. Preffer, Patricia Donahoe, David Maclaughlin, Matthew Hardy Sep 2014

Mullerian-Inhibiting Substance Type Ii Receptor Expression And Function In Purified Rat Leydig Cells, Mary Lee, C. Seah, P. Masiakos, Chantal Sottas, F. Preffer, Patricia Donahoe, David Maclaughlin, Matthew Hardy

Mary M. Lee

Mullerian-inhibiting substance (MIS), a gonadal hormone in the transforming growth factor-beta superfamily, induces Mullerian duct involution during male sexual differentiation. Mice with null mutations of the MIS ligand or receptor develop Leydig cell hyperplasia and neoplasia in addition to retained Mullerian ducts, whereas MIS-overexpressing transgenic mice have decreased testosterone concentrations and Leydig cell numbers. We hypothesized that MIS directly modulates Leydig cell proliferation and differentiated function in the maturing testis. Therefore, highly purified rat Leydig and Sertoli cells were isolated to examine cell-specific expression, binding, and function of the MIS type II receptor. These studies revealed that this receptor is …


Isolation Of The Rat Gene For Mullerian Inhibiting Substance, Christopher Haqq, Mary Lee, Richard Tizard, Mark Wysk, Janice Demarinis, Patricia Donahoe, Richard Cate Sep 2014

Isolation Of The Rat Gene For Mullerian Inhibiting Substance, Christopher Haqq, Mary Lee, Richard Tizard, Mark Wysk, Janice Demarinis, Patricia Donahoe, Richard Cate

Mary M. Lee

Mullerian inhibiting substance (MIS), a testicular glycoprotein also known as anti-Mullerian hormone, plays a key role in male sexual development by causing regression of the Mullerian duct, the anlagen of the uterus, the Fallopian tubes, and part of the vagina. MIS is also expressed in the postnatal ovary, but its precise function is still not known. We report here the complete nucleotide sequence of the rat MIS gene. Rat MIS is encoded in five exons and is synthesized as a precursor of 553 amino acids, containing a 24-amino-acid leader. Based on homology with human MIS, we predict that the rat …


Mullerian Inhibiting Substance Messenger Ribonucleic Acid Expression In Granulosa And Sertoli Cells Coincides With Their Mitotic Activity, Seiichi Hirobe, Wei He, Mary Lee, Patricia Donahoe Sep 2014

Mullerian Inhibiting Substance Messenger Ribonucleic Acid Expression In Granulosa And Sertoli Cells Coincides With Their Mitotic Activity, Seiichi Hirobe, Wei He, Mary Lee, Patricia Donahoe

Mary M. Lee

In males, Mullerian inhibiting substance (MIS) mRNA was first detected on the medial aspect of the urogenital ridge early on the morning of day 13 of gestation before testicular differentiation was evident, and localized to the more obvious Sertoli cells later on embryonic day 13. MIS transcripts remained at maximal levels between 14.5 and 17.5 days gestation, while the Mullerian duct involutes, and remained high until birth. MIS gene expression decreased progressively after birth and, as germ cell meiosis increased, became barely detectable in the Sertoli cells of the seminiferous tubules. In female rats, MIS mRNA was first detected in …


Activation Of Mglur2/3 Receptors In The Ventral Prefrontal Cortex Reverses Sensorimotor Gating Deficits Induced By A Systemic Nmda Receptor Antagonist, Bridget Valsamis, Michael Chang, Marei Typlt, Susanne Schmid Feb 2014

Activation Of Mglur2/3 Receptors In The Ventral Prefrontal Cortex Reverses Sensorimotor Gating Deficits Induced By A Systemic Nmda Receptor Antagonist, Bridget Valsamis, Michael Chang, Marei Typlt, Susanne Schmid

Anatomy and Cell Biology Publications

Prepulse inhibition (PPI) of acoustic startle is an operational measure of sensorimotor gating, which is disrupted in schizophrenia. NMDA receptor (NMDAR) antagonist induced PPI disruption has become an important pharmacological model for schizophrenia; however, knowledge of the underlying mechanism remains incomplete. This study examines the role of NMDAR in the caudal pontine reticular nucleus (PnC) and the medial prefrontal cortex (mPFC) in NMDARs antagonist induced PPI deficits, as well as the NMDA receptor subtypes involved. We administered the NMDA antagonist MK-801 locally into the caudal pontine reticular formation (PnC), where the PPI mediating pathway converges with the primary startle pathway, …


Coordinated Dynamic Gene Expression Changes In The Central Nucleus Of The Amygdala During Alcohol Withdrawal., Kate Freeman, Mary M. Staehle, Rajanikanth Vadigepalli, Gregory E Gonye, Babatunde A Ogunnaike, Jan B Hoek, James S Schwaber Jan 2013

Coordinated Dynamic Gene Expression Changes In The Central Nucleus Of The Amygdala During Alcohol Withdrawal., Kate Freeman, Mary M. Staehle, Rajanikanth Vadigepalli, Gregory E Gonye, Babatunde A Ogunnaike, Jan B Hoek, James S Schwaber

Faculty Scholarship for the College of Science & Mathematics

BACKGROUND: Chronic alcohol use causes widespread changes in the cellular biology of the amygdala's central nucleus (CeA), a GABAergic center that integrates autonomic physiology with the emotional aspects of motivation and learning. While alcohol-induced neurochemical changes play a role in dependence and drinking behavior, little is known about the CeA's dynamic changes during withdrawal, a period of emotional and physiologic disturbance.

METHODS: We used a qRT-PCR platform to measure 139 transcripts in 92 rat CeA samples from control (N = 33), chronically alcohol exposed (N = 26), and withdrawn rats (t = 4, 8, 18, 32, and 48 hours; N …


Rapid Temporal Changes In The Expression Of A Set Of Neuromodulatory Genes During Alcohol Withdrawal In The Dorsal Vagal Complex: Molecular Evidence Of Homeostatic Disturbance., Kate Freeman, Mary M. Staehle, Zeynep H Gümüş, Rajanikanth Vadigepalli, Gregory E Gonye, Carmen N Nichols, Babatunde A Ogunnaike, Jan B Hoek, James S Schwaber Oct 2012

Rapid Temporal Changes In The Expression Of A Set Of Neuromodulatory Genes During Alcohol Withdrawal In The Dorsal Vagal Complex: Molecular Evidence Of Homeostatic Disturbance., Kate Freeman, Mary M. Staehle, Zeynep H Gümüş, Rajanikanth Vadigepalli, Gregory E Gonye, Carmen N Nichols, Babatunde A Ogunnaike, Jan B Hoek, James S Schwaber

Faculty Scholarship for the College of Science & Mathematics

BACKGROUND: Chronic alcohol exposure produces neuroadaptation, which increases the risk of cellular excitotoxicity and autonomic dysfunction during withdrawal. The temporal progression and regulation of the gene expression that contributes to this physiologic and behavioral phenotype is poorly understood early in the withdrawal period. Further, it is unexplored in the dorsal vagal complex (DVC), a brainstem autonomic regulatory structure.

METHODS: We use a quantitative polymerase chain reaction platform to precisely and simultaneously measure the expression of 145 neuromodulatory genes in more than 100 rat DVC samples from control, chronically alcohol-exposed, and withdrawn rats. To gain insight into the dynamic progression and …


Supervillin Modulation Of Focal Adhesions Involving Trip6/Zrp-1, Norio Takizawa, Tara C. Smith, Thomas Nebl, Jessica Lynn Crowley, Stephen J. Palmieri, Lawrence M. Lifshitz, Anka G. Ehrhardt, Laura M. Hoffman, Mary C. Beckerle, Elizabeth J. Luna Mar 2008

Supervillin Modulation Of Focal Adhesions Involving Trip6/Zrp-1, Norio Takizawa, Tara C. Smith, Thomas Nebl, Jessica Lynn Crowley, Stephen J. Palmieri, Lawrence M. Lifshitz, Anka G. Ehrhardt, Laura M. Hoffman, Mary C. Beckerle, Elizabeth J. Luna

Elizabeth J. Luna

Cell-substrate contacts, called focal adhesions (FAs), are dynamic in rapidly moving cells. We show that supervillin (SV)--a peripheral membrane protein that binds myosin II and F-actin in such cells--negatively regulates stress fibers, FAs, and cell-substrate adhesion. The major FA regulatory sequence within SV (SV342-571) binds to the LIM domains of two proteins in the zyxin family, thyroid receptor-interacting protein 6 (TRIP6) and lipoma-preferred partner (LPP), but not to zyxin itself. SV and TRIP6 colocalize within large FAs, where TRIP6 may help recruit SV. RNAi-mediated decreases in either protein increase cell adhesion to fibronectin. TRIP6 partially rescues SV effects on stress …


The Effects Of A Resveratrol Derivative On Regulatory Behaviors And Reproductive Health In Male And Female Long-Evans Rats, Kimberly Michelle Fabick Mar 2008

The Effects Of A Resveratrol Derivative On Regulatory Behaviors And Reproductive Health In Male And Female Long-Evans Rats, Kimberly Michelle Fabick

Theses and Dissertations

Phytoestrogens are chemicals produced by plants that act like estrogens and have the ability to bind to the mammalian estrogen receptor system. The purpose of this study is to evaluate a new phytoestrogen analog called 4-acetoxy Resveratrol. Resveratrol is a phytoestrogen that has been found in the skin of grapes. Resveratrol has been shown to be able to bind to the estrogen receptors and has a similar molecular structure as estradiol. Resveratrol has been shown to have many positive health benefits such as improving cardiovascular health, serving as a neuroprotective agent, acting as an anti-inflammatory agent, working as an anti-cancer …


Crystal Structure Of The Gtpase Domain Of Rat Dynamin 1, Thomas F. Reubold, Susanne Eschenburg, Andreas Becker, Marilyn Leonard, Sandra L. Schmid, Richard B. Vallee, F. Jon Kull, Dietmar J. Manstein Jan 2005

Crystal Structure Of The Gtpase Domain Of Rat Dynamin 1, Thomas F. Reubold, Susanne Eschenburg, Andreas Becker, Marilyn Leonard, Sandra L. Schmid, Richard B. Vallee, F. Jon Kull, Dietmar J. Manstein

Dartmouth Scholarship

Here, we present the 1.9-A crystal structure of the nucleotide-free GTPase domain of dynamin 1 from Rattus norvegicus. The structure corresponds to an extended form of the canonical GTPase fold observed in Ras proteins. Both nucleotide-binding switch motifs are well resolved, adopting conformations that closely resemble a GTP-bound state not previously observed for nucleotide-free GTPases. Two highly conserved arginines, Arg-66 and Arg-67, greatly restrict the mobility of switch I and are ideally positioned to relay information about the nucleotide state to other parts of the protein. Our results support a model in which switch I residue Arg-59 gates GTP binding …


Binding Of Matrix Attachment Regions To Lamin Polymers Involves Single-Stranded Regions And The Minor Groove., M. E. Eva Ludérus, Jan L. Den Blaauwen, Oncko J. De Smit, Duane A. Compton, Roel Van Driel Jan 1994

Binding Of Matrix Attachment Regions To Lamin Polymers Involves Single-Stranded Regions And The Minor Groove., M. E. Eva Ludérus, Jan L. Den Blaauwen, Oncko J. De Smit, Duane A. Compton, Roel Van Driel

Dartmouth Scholarship

Chromatin in eukaryotic nuclei is thought to be partitioned into functional loop domains that are generated by the binding of defined DNA sequences, named MARs (matrix attachment regions), to the nuclear matrix. We have previously identified B-type lamins as MAR-binding matrix components (M. E. E. Ludérus, A. de Graaf, E. Mattia, J. L. den Blaauwen, M. A. Grande, L. de Jong, and R. van Driel, Cell 70:949-959, 1992). Here we show that A-type lamins and the structurally related proteins desmin and NuMA also specifically bind MARs in vitro. We studied the interaction between MARs and lamin polymers in molecular detail …


A Light And Electron Microscopic Study Of The Rat Olfactory Tubercle: Normal Morphology And Acetylcholinesterase Localization, James Curtis Woodley Jul 1988

A Light And Electron Microscopic Study Of The Rat Olfactory Tubercle: Normal Morphology And Acetylcholinesterase Localization, James Curtis Woodley

Biological Sciences Theses & Dissertations

A cytoarchitectural analysis of the rat olfactory tubercle using Nissl-stained coronal sections revealed that the dense cell layer (DCL) consisted of medium sized striatal cells in the cortical regions and small sized "granule" cells in the cap regions. Also delineated from this experiment was a rim of neuropil, nearly devoid of neurons as well as neuronal processes, outlining the islands of Calleja. Acetylcholinesterase (AChE) localization utilizing light microscopy revealed that the olfactory tubercles (OT) contained AChE-positive fibers that were orientated dorsoventrally in the molecular and multiform layers. The DCL consisted of only fibers en passant and putative terminals. Diisopropylfluorophosphate (DFP) …