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2012

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Full-Text Articles in Medicine and Health Sciences

Mitochondrial Morphology And Function In Neuronal Cells Under Stress, Lonnie Schneider Jan 2012

Mitochondrial Morphology And Function In Neuronal Cells Under Stress, Lonnie Schneider

All ETDs from UAB

Neurodegenerative disease encompasses a wide range of conditions and pathologies that can manifest at any age depending on the etiology. A major factor in both early onset and age-related neurodegeneration is mitochondrial dysfunction. To investigate how mitochondrial bioenergetics is affected by cellular stress, we used an in vitro culture system to examine mitochondrial function in response to oxidative stress. We also studied an in vivo model of neuronal ceroid lipofuscinosis to determine the impact of deficient autophagy-lysosomal activity on mitochondrial morphology, composition and function. In vitro we found that retinoic acid-induced differentiation of dopaminergic neuroblastoma SH-SY5Y cells exhibited increased mitochondrial …


Influence Of Daily Electrical Stimulation Of Periaqueductal Grey On Vocalization And Depressive-Like Behavior During Separation In Guinea Pigs, Jennifer Dazey Jan 2012

Influence Of Daily Electrical Stimulation Of Periaqueductal Grey On Vocalization And Depressive-Like Behavior During Separation In Guinea Pigs, Jennifer Dazey

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Maternal separation has been shown to promote the onset of depression. This early life stressor produces a biphasic response marked by an active "protest" phase followed by a passive "despair" phase in humans as well as several other species. In infant guinea pigs, active phase behaviors include increased locomotion and species-typical distress vocalizations, whereas the passive phase is marked by depressive-like behaviors including a crouched stance, eye-closure and extensive piloerection. The mechanism underlying the transition from one phase to the next is still unknown. The purpose of this study was to determine if daily stimulation of the neural pathway initiating …


Glutamate Receptor-Mediated Taurine Release From The Hippocampus During Oxidative Stress, Brian Christopher Tucker Jan 2012

Glutamate Receptor-Mediated Taurine Release From The Hippocampus During Oxidative Stress, Brian Christopher Tucker

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Oxidative stress is an important result of cerebral ischemia and has been directly linked to hippocampal swelling and cytotoxic brain edema in vitro. Swollen brain cells activate volume regulatory mechanisms including a significant efflux of the endogenous sulfonic amino acid taurine via volume-regulated anion channels (VRACs). Studies in brain slice preparations also suggest that the excitatory amino acid glutamate plays an important role in both brain tissue swelling and in cell volume regulation. We examined relationships between oxidative stress, glutamate receptor activation, cell swelling, and volume regulation in acutely prepared slices of rat hippocampus. Our results indicate that the release …


Sleep Quality, Stress, Caregiver Burden, And Quality Of Life In Maternal Caregivers Of Young Children With Bronchopulmonary Dysplasia, Christine A. Feeley Jan 2012

Sleep Quality, Stress, Caregiver Burden, And Quality Of Life In Maternal Caregivers Of Young Children With Bronchopulmonary Dysplasia, Christine A. Feeley

All ETDs from UAB

Mothers are usually the primary caregivers of young children with a chronic illness such as bronchopulmonary dysplasia (BPD), and may have no formal caregiver training. Children with BPD often require complex healthcare at home (complex medication regimens, oxygen via nasal cannula, Gastrostomy feedings, etc.), thus many maternal caregivers experience difficulty balancing the needs of their child with their own needs and other responsibilities. As such, maternal caregivers may report increased levels of stress and caregiver burden, as well as decreased quality of life (QOL). Additionally, a great number of maternal caregivers report poor sleep quality due to nighttime caregiving duties. …


Proteomic Clues To The Pathogenesis Of Alexander Disease, Daniel L. Flint Jan 2012

Proteomic Clues To The Pathogenesis Of Alexander Disease, Daniel L. Flint

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Since the initial report identifying mutations in GFAP as the primary genetic defect in the astrogliopathy Alexander Disease (AxD) much progress has been made in elucidating the molecular details underpinning the pathogenic role of mutant GFAP in astrocytes. In particular, data collected from mouse, fly, and cell culture models of AxD have isolated several prominent cellular changes that are associated with mutant GFAP expression including oxidative stress, proteasome inhibition, reduced expression of the astrocyte glutamate transporter GLT-1, and loss of neurons; these models have also successfully recapitulated the pathological hallmark of AxD--protein aggregates known as Rosenthal fibers (RFs). To date, …


Myosin Ii Regulates Actin Dynamics Critical For Structural Plasticity And Fear Memory Formation, Cristin Gavin Jan 2012

Myosin Ii Regulates Actin Dynamics Critical For Structural Plasticity And Fear Memory Formation, Cristin Gavin

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Dynamic changes to the actin cytoskeleton are required for synaptic plasticity and long-term memory formation. However, the molecular mechanisms that mediate filamentous actin (F-actin) dynamics during both activity-dependent synaptic potentiation and long-term memory encoding are poorly understood. Myosin II motor proteins are highly expressed in actin-rich growth structures in neurons, including dendritic spines. Recent work demonstrates that these molecular machines mobilize F-actin in response to synaptic stimulation and are required for memory encoding in CA1 hippocampus of rodents. The aims of this project were two-fold. First, we sought to establish if myosin II regulates actin filament polymerization necessary for structural …


Fat Distribution And Metabolic Health: The Effects Of Macronutrient Manipulation On Fat Distribution, Weight Loss, And Glucose Metabolism, Amy Miskimon Goss Jan 2012

Fat Distribution And Metabolic Health: The Effects Of Macronutrient Manipulation On Fat Distribution, Weight Loss, And Glucose Metabolism, Amy Miskimon Goss

All ETDs from UAB

Fat distribution pattern may contribute to risk of development of metabolic diseases such and type 2 diabetes and cardiovascular disease. However, the precise nature of the relationships between adipose tissue depots and metabolic health remains controversial. Additionally, further research is needed to identify optimal dietary approaches to reduce disease risk and visceral adiposity among overweight and obese individuals, who may already be on a trajectory for development of metabolic disease. Therefore, the goal of this project was to examine relationships of adipose tissue depots with insulin sensitivity, and then to determine if diets differing in CHO and fat content can …


Antiphagocytic Factors Of Mycoplasma Pulmonis, Brandon Michael Shaw Jan 2012

Antiphagocytic Factors Of Mycoplasma Pulmonis, Brandon Michael Shaw

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Mycoplasma pulmonis is a murine respiratory pathogen and is used as a model for studying chronic mycoplasmal respiratory disease. This organism has been used by many in vivo and in vitro studies to gain a better understanding of host-pathogen interactions in chronic respiratory infection. Studies have shown that alveolar macrophages play an important role in the removal of this pathogen from the host. Given that M. pulmonis is able to produce a chronic disease state, this organism should produce antiphagocytic factors that aid in avoidance of killing by alveolar macrophages. The Vsa proteins are involved in the avoidance of killing …


Cardiovascular Disease Knowledge And Risk Perception Among Women With Recent Preeclampsia: Interventional Education In Disease Management And Prevention, Patsy M. Spratling Jan 2012

Cardiovascular Disease Knowledge And Risk Perception Among Women With Recent Preeclampsia: Interventional Education In Disease Management And Prevention, Patsy M. Spratling

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There is a growing body of evidence linking preeclampsia to future development of cardiovascular disease (CVD). Although CVD is well-known as the leading cause of death in women, a lack of evidence exists demonstrating that women with preeclampsia are routinely informed of their risks for future CVD. The specific aims of this study were to: (1) examine the levels of CVD knowledge and perception of CVD risk pre-CVD education; (2) explore relationships among age, race, parity, marital status, previous preeclampsia, income, education, CVD knowledge, and perception of CVD risk; and (3) examine the effect of a postpartum CVD educational intervention …


Measuring Disease Activity And Use Of Complementary And Alternative Medicine In African-Americans With Rheumatoid Arthritis, Ashutosh Tamhane Jan 2012

Measuring Disease Activity And Use Of Complementary And Alternative Medicine In African-Americans With Rheumatoid Arthritis, Ashutosh Tamhane

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The aims of this project were to: 1) compare disease activity scores 28 joints (DAS28) based on erythrocyte sedimentation rate (ESR) versus that based on C-reactive protein (CRP), and 2) describe prevalence of complementary and alternative medicine (CAM) use and examine differences of CAM use stratified by disease duration and sex. This analysis included participants from the Consortium for the Longitudinal Evaluation of African Americans with Early Rheumatoid Arthritis (CLEAR) Registry. Using tender and swollen joint counts separate ESR-based and CRP-based DAS28 scores (DAS28-ESR3 and DAS28-CRP3) were calculated, as were DAS28-ESR4 and DAS28-CRP4, which included the patient¡¯s assessment of disease …


Characterization Of Pleiotrophin And Receptor Protein Tyrosine Phosphatase Beta/Zeta In Odontoblast And Osteoblast Cell Lines, Amena Tamkenath Jan 2012

Characterization Of Pleiotrophin And Receptor Protein Tyrosine Phosphatase Beta/Zeta In Odontoblast And Osteoblast Cell Lines, Amena Tamkenath

All ETDs from UAB

Pleiotrophin (PTN) is an extracellular matrix-associated growth factor and chemokine expressed in mesodermal and ectodermal cells. It plays an important role in osteoblast recruitment and differentiation. PTN has two well-known physiological receptors, protein tyrosine phosphatase beta/zeta (RPTPRZ1), and N-syndecan. Protein tyrosine phosphatases are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins. Protein tyrosine phosphorylation is a common post-translation modification that can create novel recognition motifs for protein interactions and cellular localization, affect protein stability and regulate enzyme activity. Osteoblasts have recently been found to express the short transmembrane isoform of RPTP beta/zeta but nothing …


Hepatic Effect Of Inhaled Ozone In Sprague-Dawley Rat, Whitney Slone Theis Jan 2012

Hepatic Effect Of Inhaled Ozone In Sprague-Dawley Rat, Whitney Slone Theis

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Ozone (O3) is a primary component of photochemical smog and represents a serious public health concern as more than 50% of the U.S. population lives in areas exceeding national ambient air quality standards for this toxic pollutant. Recent findings indicate that the effects of inhaled O3 extend to extra-pulmonary tissues like the heart and liver. We hypothesize that inhaled O3 exposure-related events in the lung will cause downstream alterations in the liver proteome. To test this, we exposed male Sprague-Dawley rats to 0.5 ppm ozone for 8 hr a day for 5 days. After exposures, livers were removed and proteomic …


Glutamate Release And Uptake At Cerebellar Synapses, Ming-Chi Tsai Jan 2012

Glutamate Release And Uptake At Cerebellar Synapses, Ming-Chi Tsai

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Glutamate mediates excitatory synaptic transmission in the central nervous system (CNS). Regulation of glutamate release and uptake shapes the spatiotemporal dynamics of glutamate at and around synapses to influence information transfer between neural cells. This dissertation focuses on the modulation of glutamate release and uptake at excitatory synapses of cerebellar Purkinje cells (PC). In the first project we show that differential expression of PC glutamate transporters controls the amount of glutamate entering the extrasynaptic space, thereby influencing the excitatory responses in surrounding Bergmann glia. This work provides the first evidence that neuronal glutamate uptake affects glial glutamatergic signaling. In the …


An Exploration Of Factors Associated With Pre-Diabetes In The Reasons For Geographic And Racial Differences In Stroke (Regards) Study Cohort, Loretta Taylor Lee Jan 2012

An Exploration Of Factors Associated With Pre-Diabetes In The Reasons For Geographic And Racial Differences In Stroke (Regards) Study Cohort, Loretta Taylor Lee

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Pre-diabetes is a major contributor to increased morbidity and mortality in the US. Without proper and timely intervention the majority of individuals with pre-diabetes will develop Type 2 diabetes. African Americans (AA) and people living in the Stroke Belt have increased odds of developing pre-diabetes compared to Whites and people living outside the Stroke Belt. While several covariates have been identified as contributors to the increased odds of pre-diabetes there is little consensus on which covariates may be responsible for the disparities of pre-diabetes. The reasons for disparities in pre-diabetes are complex and require further investigation. This study explored the …


Development Of An Adenoviral Vector Platform For Selective Gene Delivery To Neurons, Travis Benjamin Lewis Jan 2012

Development Of An Adenoviral Vector Platform For Selective Gene Delivery To Neurons, Travis Benjamin Lewis

All ETDs from UAB

Parkinson disease (PD) is a devastating movement disorder affecting between 500,000 and 1,000,000 individuals in the United States alone, and for which there is currently no cure. Therapies such as dopamine replacement help initially, but with disease progression these lose efficacy and do not alter the underlying degenerative process. Gene therapy is the delivery of exogenous genetic material to correct an underlying disorder. A major advantage of this approach is the ability to distribute potent therapies to specific targets over an extended duration, properties necessary for the treatment of progressive degenerative diseases such as PD. A number of clinical trials …


The Effect Of Acetylcholine Receptor Activation On The Response Properties Of Retinal Ganglion Cells, Ye Long Jan 2012

The Effect Of Acetylcholine Receptor Activation On The Response Properties Of Retinal Ganglion Cells, Ye Long

All ETDs from UAB

Acetylcholine (ACh) is the first identified neurotransmitter and acts in areas including the peripheral nervous system (PNS) and the central nervous system (CNS). The effects of ACh are mediated by nicotinic and muscarinic acetylcholine receptors (AChRs), both of which are extensively distributed in CNS, including the retina. The expression and distribution of nicotinic AChRs (nAChRs) and muscarinic AChRs (mAChRs) have been studied with RT-PCR, western blot, and immunohistochemical techniques in the retinas of different species (Kaneda et al., 1995; Keyser et al., 2000; Yamada et al., 2003; Strang et al., 2005; Dmitrieva et al., 2007; Liu et al., 2009; Strang …


Regulation Of Membrane Traffic By The Big2 Member Of Guanine Nucleotide Exchange Factors, Jason Lowery Jan 2012

Regulation Of Membrane Traffic By The Big2 Member Of Guanine Nucleotide Exchange Factors, Jason Lowery

All ETDs from UAB

Vesicular transport is an essential cellular process that facilitates the movement of molecules within a cell. The importance of vesicular transport is highlighted by numerous human diseases that result from mutations affecting protein trafficking. The Brefeldin A-inhibited guanine nucleotide exchange factor 2 (BIG2) has emerged as a key regulator of protein trafficking within the late secretory pathway, between the trans-Golgi Network (TGN) and endosomal compartments and within the recycling endosomal pathway. Mutations in BIG2 lead to Autosomal Recessive Periventricular Heterotopia with Microcephly (ARPHM), a disorder characterized by severe brain malformations. BIG2 stimulates nucleotide exchange of GDP for GTP on ADP-ribosylation …


Localization Of Proteins Involved In Trafficking In Frog And Mouse Retina, Amie Marsh Jan 2012

Localization Of Proteins Involved In Trafficking In Frog And Mouse Retina, Amie Marsh

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The connecting cilium serves as the major route for protein transport from the inner to outer segment of photoreceptor cells. The hypothesis that all Congenital Stationary Night Blindness (CSNB) rhodopsin mutants travel properly to the rod outer segment in Xenopus laevis will be tested by preparing transgenic X. laevis expressing a rhodopsin mutation found in human CSNB, A295V. In addition, probing for the existence of potential proteins involved in regulating rhodopsin trafficking and monitoring their localization will contribute to a better understanding of the underlying pathway of intracellular photoreceptor trafficking.


The Effects Of Direct To Consumer Advertising On Healthcare Utilization Among Medicaid Children With Asthma, Luceta C. Mcroy Jan 2012

The Effects Of Direct To Consumer Advertising On Healthcare Utilization Among Medicaid Children With Asthma, Luceta C. Mcroy

All ETDs from UAB

National guidelines recommend treatment of asthma with preventive long term medication, but adherence remains low, resulting in high healthcare utilization among those affected by the chronic disease. The increase in DTCA since the easing of restrictions by the FDA in 1997 has prompted much debate on the effects of the DTCA, with critics arguing that it is harmful while proponents see many benefits such as increased medication adherence. This study examines the impact of DTCA on healthcare utilization and asthma medication use by combining Medicaid administrative data and a national advertising data set on asthma medication from 1999 to 2002. …


Mechanisms Of Lrrk2 Regulation, Philip J. Webber Jan 2012

Mechanisms Of Lrrk2 Regulation, Philip J. Webber

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Non-synonymous mutations in LRRK2 are the most common known cause of familial and sporadic Parkinson's disease (PD). The dominant inheritance of these mutations in familial PD suggests a gain-of-function mechanism. Increased kinase activity observed in the most common PD associated LRRK2 mutation G2019S suggests that kinase activity is central to disease. However, not all mutations associated with disease are reported to alter kinase activity and controversy exists in the literature about the effects of mutations appearing in the GTPase domain on kinase activity. The studies conducted as a part of this work aim to characterize the mechanisms that regulate LRRK2 …


Biochemical And Cellular Mechanisms For The Antineoplastic Properties Of Sulindac, Jason Derek Whitt Jan 2012

Biochemical And Cellular Mechanisms For The Antineoplastic Properties Of Sulindac, Jason Derek Whitt

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ABSTRACT The nonsteroidal anti-inflammatory drug (NSAID) sulindac has displayed the ability to inhibit the proliferation of colorectal cancer (CRC) cells and to increase the sensitivity of multidrug resistant (MDR) cancer cells to a wide variety of chemotherapeutic agents. The antineoplastic activity of sulindac has been attributed to inhibition of the prostaglandin producing enzyme COX-2, but the exact mechanism remains elusive and the inhibition of prostaglandin synthesis can result in gastrointestinal, hepatic, and cardiovascular toxicities. Enzymatic, cellular, and imaging assays were used to identify mechanisms that could contribute to the antiproliferative and apoptotic activity of sulindac. Screening of more than 500 …


Regulation And Function Of Interleukin-21-Producing T Cells And Immune-Mediated Control Of Hiv-1 Infection, Latonya Denise Williams Jan 2012

Regulation And Function Of Interleukin-21-Producing T Cells And Immune-Mediated Control Of Hiv-1 Infection, Latonya Denise Williams

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CD8 T cells play a critical role in controlling intracellular pathogens, particularly viruses. However, during persistent viral infections, such as human immunodeficiency virus-1 (HIV-1) infection, virus-specific CD8 T cells become increasingly impaired by poorly understood mechanisms. Massive CD4 T cell depletion is a hallmark of HIV-1 infection and is associated with CD8 T cell dysfunction and ineffective viral containment. CD4 T cells provide critical helper signals to CD8 T cells, especially during uncontrolled viral infections. Mouse models of chronic viral infection implicate interleukin-21 (IL-21), produced primarily by CD4 T cells, as a vital factor necessary for the maintenance of fully …


Influence Of Surface Treatment Of Y-Tzp And Luting Cements On Retention Of Y-Tzp Crown, Mehdi Karimipour-Saryazdi Jan 2012

Influence Of Surface Treatment Of Y-Tzp And Luting Cements On Retention Of Y-Tzp Crown, Mehdi Karimipour-Saryazdi

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Clinicians for a single tooth restoration, due to improved esthetics, often select all ceramic crowns. Zirconium Oxide has been utilized for many years to full fill the requirement of esthetics, high mechanical properties and biocompatibility. The purpose of this study is to evaluate the effect of different surface treatments and luting agents on retention of a zirconium oxide crown. Material and Methods: Ninety extracted teeth were obtained. Teeth were mounted in Ortho JetTM resin (Lang Dental Manufacturing Co., Inc. IL, USA). Occlusal surface was cut flat using Isomet (Buhler Ltd). Diamond burs were used to cut axial walls under water …


The Effect Of Structured Background On Smooth Pursuit With Real And Simulated Central Scotoma, Thomas Keith Jan 2012

The Effect Of Structured Background On Smooth Pursuit With Real And Simulated Central Scotoma, Thomas Keith

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The purpose of the study was to better understand the role of the fovea in smooth pursuit eye movements in human subjects. The research entailed a systematical study of a previously unstudied condition where the foveal inputs of both the background and the pursuit target were eliminated through simulation but the anatomic fovea was intact; and a comprehensive study of smooth pursuit eye movements of human subjects with real central scotoma. Ten normally sighted subjects (NS) and three central scotoma subjects (CS) were asked to visually pursuit a 0.87o yellow dot moving along either a horizontal or a vertical trajectory …


Trajectories Of Depressive Symptoms And Illicit Drug Use: Longitudinal Temporal Associations And Comorbidity In A Community Sample Of Adults, Yulia Khodneva Jan 2012

Trajectories Of Depressive Symptoms And Illicit Drug Use: Longitudinal Temporal Associations And Comorbidity In A Community Sample Of Adults, Yulia Khodneva

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Cross-sectional studies of the community and treatment samples suggest substantial comorbidity between depression and illicit drug use disorders. Controversy exists whether such pattern of comorbidity is seen among drug using behaviors and depressive symptoms that fall short of the DSM-IV criteria for a clinical disorder. This dissertation research applied principles of the life course perspective and trajectory modeling to describe heterogeneity and comorbidity of subthreshold depressive symptoms with opioid, cocaine and amphetamine use in middle age. Secondary analysis of community-dwelling adults from the Coronary Artery Risk Development in Young Adults (CARDIA) study was performed. The CARDIA cohort, N=5115 at inception …


Maturation Of The Carotid Body Oxygen-Sensor During Rat Development, Julia Paulet Jan 2012

Maturation Of The Carotid Body Oxygen-Sensor During Rat Development, Julia Paulet

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Carotid bodies (CB) are paired, oxygen-sensing organs located in the bifurcation of the carotid artery that act as peripheral chemoreceptors in the detection of hypoxic, hypercapnic and acidotic levels in the arterial blood. CBs respond to these fluctuations in blood gases by initiating firing of the carotid sinus nerve. This ultimately results in the appropriate ventilatory change to restore blood gases to their physiological levels. Studies have shown that the hypoxic response of the carotid body in juvenile mammals is low, but as maturation occurs this response is strengthened and clearly exhibited in adults. One theory suggests mitochondria play a …


Effects Of Elevated Glucocorticoid Levels On Dentate Gyrus Development, Zachary Dale Vallandingham Jan 2012

Effects Of Elevated Glucocorticoid Levels On Dentate Gyrus Development, Zachary Dale Vallandingham

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Exogenous glucocorticoids are commonly used in modern medications and animal studies examining the effects of glucocorticoids on the developing brain report inconsistent results. Recent reports have questioned the reliability of available drug delivery methods in mice (Herrmann et al., 2009). In our laboratory, variable behavioral results using trace eyeblink conditioning (EBC) suggest that we may be having similar problems delivering glucoroticoids to developing rat pups (Claflin et al., 2005, 2011). Subcutaneous pellets and osmotic minipumps resulted in impaired learning during trace eyeblink conditioning whereas subcutaneous injection of corticosterone (CORT) resulted in facilitation of learning on the same task. One of …


Electrical Brain Stimulation And Depressive-Like Behavior In Guinea Pigs, Nadia Kardegar Jan 2012

Electrical Brain Stimulation And Depressive-Like Behavior In Guinea Pigs, Nadia Kardegar

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Maternal separation in guinea pigs produces a biphasic response consisting of an active behavior phase (vocalizations and locomotor activity) followed by a phase of passive depressive-like behavior (crouched stance, piloerection, and eye closure). The mechanism for the transition from the active to the passive phase is unknown. One suggestion is that continual activity of neural circuitry producing active behavior eventually leads to the expression of passive behaviors. The purpose of this study was to test this possibility. Guinea pigs were assigned to experimental and control groups. The experimental group received daily stimulation of the bed nucleus stria terminalis (BNST) to …