Life Sciences Commons^™

Altered Gating Of KV1.4 In The Nucleus Accumbens Suppresses Motivation For Reward, Bernadette O'Donovan, Adewale Adeluyi, Erin L Anderson, Robert D. Cole, Jill R. Turner, Pavel I. Ortinski

Neuroscience Faculty Publications

Deficient motivation contributes to numerous psychiatric disorders, including withdrawal from drug use, depression, schizophrenia, and others. Nucleus accumbens (NAc) has been implicated in motivated behavior, but it remains unclear whether motivational drive is linked to discrete neurobiological mechanisms within the NAc. To examine this, we profiled cohorts of Sprague-Dawley rats in a test of motivation to consume sucrose. We found that substantial variability in willingness to exert effort for reward was not associated with operant responding under low-effort conditions or stress levels. Instead, effort-based motivation was mirrored by a divergent NAc shell transcriptome with differential regulation at potassium and dopamine …

Protection Effect Of Exogenous Fibroblast Growth Factor 21 On The Kidney Injury In Vascular Calcification Rats, Yu-Chen Shi, Wei-Wei Lu, Yue-Long Hou, Kun Fu, Feng Gan, Shu-Juan Cheng, Shao-Ping Wang, Yong-Fen Qi, Jing-Hua Liu

Pharmacology and Nutritional Sciences Faculty Publications

Background: Chronic kidney disease (CKD) is closely related to the cardiovascular events in vascular calcification (VC). However, little has known about the characteristics of kidney injury caused by VC. Fibroblast growth factor 21 (FGF21) is an endocrine factor, which takes part in various metabolic actions with the potential to alleviate metabolic disorder diseases. Even FGF21 has been regarded as a biomarker in CKD, the role of FGF21 in CKD remains unclear. Therefore, in this study, we evaluate the FGF21 on the kidney injury in VC rats.

Methods: The male Sprague-Dawley rats were divided into three groups: (1) control group, (2) …

Associative Learning Contributes To The Increased Water Intake Observed After Daily Injections Of Angiotensin Ii, Maggie Postolache, Jessica Santollo, Derek Daniels

Biology Faculty Publications

Daily injections of angiotensin II (AngII) cause a progressive increase of water intake that resembles a classically ascribed non-associative sensitization. Consistent with the presumption that the observed increase in intake was sensitization, we hypothesized that it resulted from a pharmacological interaction between AngII and its receptor. To test this hypothesis, and remove the influence of drinking itself, we implemented a delay in water access after injection of AngII (icv) on four consecutive ‘induction days,’ and then measured intake on the next day (‘test day’) when rats were allowed to drink immediately after AngII. The delay in water access effectively reduced …

Sex Differences In The Drinking Response To Angiotensin Ii (Angii): Effect Of Body Weight, Jessica Santollo, Ann-Marie Torregrossa, Derek Daniels

Biology Faculty Publications

Sex differences in fluid intake stimulated by angiotensin II (AngII) have been reported, but the direction of the differences is inconsistent. To resolve these discrepancies, we measured water intake by male and female rats given AngII. Males drank more than females, but when intake was normalized to body weight, the sex difference was reversed. Weight-matched males and females, however, had no difference in intake. Using a linear mixed model analysis, we found that intake was influenced by weight, sex, and AngII dose. We used linear regression to disentangle these effects further. Comparison of regression coefficients revealed sex and weight differences …

The Effects Of Nicotine In The Neonatal Quinpirole Rodent Model Of Psychosis: Neural Plasticity Mechanisms And Nicotinic Receptor Changes, Daniel J. Peterson, W. Drew Gill, John M. Dose, Donald B. Hoover, James R. Pauly, Elizabeth D. Cummins, Katherine C. Burgess, Russell W. Brown

Pharmaceutical Sciences Faculty Publications

Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal’s lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1 mg/kg) or saline from postnatal days (P)1–21. Animals were given …

The Effect Of Sazetidine-A And Other Nicotinic Ligands On Nicotine Controlled Goal-Tracking In Female And Male Rats, S. Charntikov, A. M. Falco, K. Fink, Linda P. Dwoskin, R. A. Bevins

Pharmaceutical Sciences Faculty Publications

Nicotine is the primary addictive component of tobacco products and its complex stimulus effects are readily discriminated by humans and non-human animals. Previous preclinical research investigating directly the nature of the nicotine stimulus has been limited to male rodents. The current study began to address this significant gap in the literature by training female and male rats to discriminate 0.4 mg/kg nicotine from saline in the discriminated goal-tracking task. In this task, access to sucrose was intermittently available on nicotine session. On saline session, intermixed with nicotine sessions on separate days, sucrose was not available. Both sexes acquired the discrimination …

Mechanical Conflict System: A Novel Operant Method For The Assessment Of Nociceptive Behavior, Steven E. Harte, Jessica B. Meyers, Renee R. Donahue, Bradley K. Taylor, Thomas J. Morrow

Physiology Faculty Publications

A new operant test for preclinical pain research, termed the Mechanical Conflict System (MCS), is presented. Rats were given a choice either to remain in a brightly lit compartment or to escape to a dark compartment by crossing an array of height-adjustable nociceptive probes. Latency to escape the light compartment was evaluated with varying probe heights (0, .5, 1, 2, 3, and 4 mm above compartment floor) in rats with neuropathic pain induced by constriction nerve injury (CCI) and in naive control rats. Escape responses in CCI rats were assessed following intraperitoneal administration of pregabalin (10 and 30 mg/kg), morphine …

AΒ40 Reduces P-Glycoprotein At The Blood-Brain Barrier Through The Ubiquitin-Proteasome Pathway, Anika M. S. Hartz, Yu Zhong, Andrea Wolf, Harry Levine Iii, David S. Miller, Björn Bauer

Sanders-Brown Center on Aging Faculty Publications

Failure to clear amyloid-β (Aβ) from the brain is in part responsible for Aβ brain accumulation in Alzheimer's disease (AD). A critical protein for clearing Aβ across the blood–brain barrier is the efflux transporter P-glycoprotein (P-gp) in the luminal plasma membrane of the brain capillary endothelium. P-gp is reduced at the blood–brain barrier in AD, which has been shown to be associated with Aβ brain accumulation. However, the mechanism responsible for P-gp reduction in AD is not well understood. Here we focused on identifying critical mechanistic steps involved in reducing P-gp in AD. We …

Blockade Of Astrocytic Calcineurin/Nfat Signaling Helps To Normalize Hippocampal Synaptic Function And Plasticity In A Rat Model Of Traumatic Brain Injury, Jennifer L. Furman, Pradoldej Sompol, Susan D. Kraner, Melanie M. Pleiss, Esther J. Putman, Jacob Dunkerson, Hafiz Mohmmad Abdul, Kelly N. Roberts, Stephen William Scheff, Christopher M. Norris

Pharmacology and Nutritional Sciences Faculty Publications

Increasing evidence suggests that the calcineurin (CN)-dependent transcription factor NFAT (Nuclear Factor of Activated T cells) mediates deleterious effects of astrocytes in progressive neurodegenerative conditions. However, the impact of astrocytic CN/NFAT signaling on neural function/recovery after acute injury has not been investigated extensively. Using a controlled cortical impact (CCI) procedure in rats, we show that traumatic brain injury is associated with an increase in the activities of NFATs 1 and 4 in the hippocampus at 7 d after injury. NFAT4, but not NFAT1, exhibited extensive labeling in astrocytes and was found throughout the axon/dendrite layers of CA1 and the dentate …

Dietary Supplementation With Organoselenium Accelerates Recovery Of Bladder Expression, But Does Not Improve Locomotor Function, Following Spinal Cord Injury, Carolyn A. Meyer, Ranjana Singh, Mackenzie T. Jones, Chen-Guang Yu, Ronan F. Power, James W. Geddes

Spinal Cord and Brain Injury Research Center Faculty Publications

Selenium is an essential element required for activity of several antioxidant enzymes, including glutathione peroxidase. Because of the critical role of the antioxidant system in responding to traumatic events, we hypothesized that dietary selenium supplementation would enhance neuroprotection in a rodent model of spinal cord injury. Rats were maintained on either a control or selenium-enriched diet prior to, and following, injury. Dietary selenium supplementation, provided as selenized yeast added to normal rat chow, resulted in a doubling of selenium levels in the spinal cord. Dietary selenium reduced the time required for recovery of bladder function following thoracic spinal cord injury. …

Rod Microglia: Elongation, Alignment, And Coupling To Form Trains Across The Somatosensory Cortex After Experimental Diffuse Brain Injury, Jenna M. Ziebell, Samuel E. Taylor, Tuoxin Cao, Jordan L. Harrison, Jonathan Lifshitz

Neuroscience Faculty Publications

BACKGROUND: Since their discovery, the morphology of microglia has been interpreted to mirror their function, with ramified microglia constantly surveying the micro-environment and rapidly activating when changes occur. In 1899, Franz Nissl discovered what we now recognize as a distinct microglial activation state, microglial rod cells (Stäbchenzellen), which he observed adjacent to neurons. These rod-shaped microglia are typically found in human autopsy cases of paralysis of the insane, a disease of the pre-penicillin era, and best known today from HIV-1-infected brains. Microglial rod cells have been implicated in cortical 'synaptic stripping' but their exact role has remained unclear. This is …

Rat Brain Pro-Oxidant Effects Of Peripherally Administered 5 Nm Ceria 30 Days After Exposure, Sarita S. Hardas, Rukhsana Sultana, Govind Warrier, Mo Dan, Rebecca L. Florence, Peng Wu, Eric A. Grulke, Michael T. Tseng, Jason M. Unrine, Uschi M. Graham, Robert A. Yokel, D. Allan Butterfield

Chemistry Faculty Publications

The objective of this study was to determine the residual pro-or anti-oxidant effects in rat brain 30 days after systemic administration of a 5 nm citrate-stabilized ceria dispersion. A ∼4% aqueous ceria dispersion was iv-infused (0 or 85 mg/kg) into rats which were terminated 30 days later. Ceria concentration, localization, and chemical speciation in the brain was assessed by inductively coupled plasma mass spectrometry (ICP-MS), light and electron microscopy (EM), and electron energy loss spectroscopy (EELS), respectively. Pro- or anti-oxidant effects were evaluated by measuring levels of protein carbonyls (PC), 3-nitrotyrosine (3NT), and protein-bound-4-hydroxy-2-trans-nonenal (HNE) in the hippocampus, cortex, and …

Distribution, Elimination, And Biopersistence To 90 Days Of A Systemically Introduced 30 Nm Ceria-Engineered Nanomaterial In Rats, Robert A. Yokel, Tu C. Au, Robert Macphail, Sarita S. Hardas, D. Allan Butterfield, Rukhsana Sultana, Michael Goodman, Michael T. Tseng, Mo Dan, Hamed Haghnazar, Jason M. Unrine, Uschi M. Graham, Peng Wu, Eric A. Grulke

Pharmaceutical Sciences Faculty Publications

Nanoceria is used as a catalyst in diesel fuel, as an abrasive in printed circuit manufacture, and is being pursued as an antioxidant therapeutic. Our objective is to extend previous findings showing that there were no reductions of cerium in organs of the mononuclear phagocyte (reticuloendothelial) system up to 30 days after a single nanoscale ceria administration. An ~5% aqueous dispersion of citrate-stabilized 30 nm ceria, synthesized and characterized in-house, or vehicle, was iv infused into rats terminated 1, 7, 30, or 90 days later. Cageside observations were obtained daily, body weight weekly. Daily urinary and fecal cerium outputs were …

Striatal Neuroinflammation Promotes Parkinsonism In Rats, Dong-Young Choi, Mei Liu, Randy L. Hunter, Wayne A. Cass, Jignesh D. Pandya, Patrick G. Sullivan, Eun-Joo Shin, Hyoung-Chun Kim, Don M. Gash, Guoying Bing

Neuroscience Faculty Publications

BACKGROUND: Sporadic Parkinson's disease (PD) is a progressive neurodegenerative disorder with unknown cause, but it has been suggested that neuroinflammation may play a role in pathogenesis of the disease. Neuroinflammatory component in process of PD neurodegeneration was proposed by postmortem, epidemiological and animal model studies. However, it remains unclear how neuroinflammatory factors contribute to dopaminergic neuronal death in PD.

FINDINGS: In this study, we analyzed the relationship among inducible nitric oxide synthase (iNOS)-derived NO, mitochondrial dysfunction and dopaminergic neurodegeneration to examine the possibility that microglial neuroinflammation may induce dopaminergic neuronal loss in the substantia nigra. Unilateral injection of lipopolysaccharide (LPS) …

Pioglitazone Inhibition Of Lipopolysaccharide-Induced Nitric Oxide Synthase Is Associated With Altered Activity Of P38 Map Kinase And Pi3k/Akt, Bin Xing, Tao Xin, Randy Lee Hunter, Guoying Bing

Neuroscience Faculty Publications

BACKGROUND: Previous studies have suggested that peroxisome proliferator activated receptor-gamma (PPAR-gamma)-mediated neuroprotection involves inhibition of microglial activation and decreased expression and activity of inducible nitric oxide synthase (iNOS); however, the underlying molecular mechanisms have not yet been well established. In the present study we explored: (1) the effect of the PPAR-gamma agonist pioglitazone on lipopolysaccharide (LPS)-induced iNOS activity and nitric oxide (NO) generation by microglia; (2) the differential role of p38 mitogen-activated protein kinase (p38 MAPK), c-Jun NH(2)-terminal kinase (JNK), and phosphoinositide 3-kinase (PI3K) on LPS-induced NO generation; and (3) the regulation of p38 MAPK, JNK, and PI3K by pioglitazone. …

Prenatal Cocaine Exposure Alters Alpha2 Receptor Expression In Adolescent Rats, Rosemarie M. Booze, David R. Wallace, Janelle M. Silvers, Barbara J. Strupp, Diane M. Snow, Charles F. Mactutus

Neuroscience Faculty Publications

BACKGROUND: Prenatal cocaine exposure produces attentional deficits which to persist through early childhood. Given the role of norepinephrine (NE) in attentional processes, we examined the forebrain NE systems from prenatal cocaine exposed rats. Cocaine was administered during pregnancy via the clinically relevant intravenous route of administration. Specifically, we measured alpha2-adrenergic receptor (alpha2-AR) density in adolescent (35-days-old) rats, using [3H]RX821002 (5 nM).

RESULTS: Sex-specific alterations of alpha2-AR were found in the hippocampus and amygdala of the cocaine-exposed animals, as well as an upregulation of alpha2-AR in parietal cortex.

CONCLUSION: These data suggest that prenatal cocaine exposure results in a persistent alteration …

Manganese Distribution Across The Blood-Brain Barrier. Iv. Evidence For Brain Influx Through Store-Operated Calcium Channels, Janelle S. Crossgrove, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is a required co-factor for many ubiquitous enzymes; however, chronic Mn overexposure can cause manganism, a parkinsonian-like syndrome. Previous studies showed Mn influx into brain is carrier-mediated, though the putative carrier(s) were not established. Studies conducted with cultured bovine brain microvascular endothelial cells (bBMECs), which comprise the blood–brain barrier, revealed ⁵⁴Mn (II) uptake positively correlated with pH, was temperature-dependent, and was sodium- and energy-independent. Brain ⁵⁴Mn uptake correlated inversely with calcium (Ca) concentration, but ⁴⁵Ca uptake was unaltered by high Mn concentration. Lanthanum (La), a non-selective inhibitor of several Ca channel types, as well as …

Manganese Distribution Across The Blood-Brain Barrier. I. Evidence For Carrier-Mediated Influx Of Managanese Citrate As Well As Manganese And Manganese Transferrin, Janelle S. Crossgrove, David D. Allen, Bonny L. Bukaveckas, Susan S. Rhineheimer, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Manganese (Mn) is an essential element and a neurotoxicant. Regulation of Mn movement across the blood–brain barrier (BBB) contributes to whether the brain Mn concentration is functional or toxic. In plasma, Mn associates with water, small molecular weight ligands and proteins. Mn speciation may influence the kinetics of its movement through the BBB. In the present work, the brain influx rates of ⁵⁴Mn²⁺, ⁵⁴Mn citrate and ⁵⁴Mn transferrin (⁵⁴Mn Tf) were determined using the in situ brain perfusion technique. The influx rates were compared to their predicted diffusion rates, which were determined from …