15 Matching Results

Search Results

Advanced search parameters have been applied.

Investigation of Inhibitory Influences in Neuronal Monolayer Networks Cultured from Mouse Spinal Cord

Description: The effects of the inhibitory neurotransmitters gammaamino butyric acid (GABA) and glycine were characterized on spontaneous activity recorded from mouse spinal cord cultures. The GABA concentration which completely inhibited burst activity was chosen as a quantifiable measure of culture drug response and was used to 1) assess interculture and intraculture variability, 2) determine the influence of culture age and initial activity on GABA responses, and 3) compare the GABA responses between networks obtained from whole spinal cord and ventral half spinal cord. Results showed that 1) no significant variability existed either within or among cultures, 2) the initial culture activity directly affected GABA responses, 3) the culture age had no effect on GABA responses, and 4) there was no significant difference in GABA responses between the two spinal cord tissues.
Date: August 1992
Creator: Jordan, Russell S. (Russell Stall)
Partner: UNT Libraries

In Vitro Investigations of Antibiotic Influences on Nerve Cell Network Responses to Pharmacological Agents

Description: Neuronal networks, derived from mouse embryonic frontal cortex (FC) tissue grown on microelectrode arrays, were used to investigate effects of gentamicin pretreatment on pharmacological response to the L-type calcium channel blocker, verapamil. Gentamicin is a broad spectrum antibiotic used to control bacterial contamination in cell culture. The addition of gentamicin directly to medium affects the pharmacological and morphological properties of the cells in culture. A reproducible dose response curve to verapamil from untreated cultures was established and the mean EC50 was calculated to be 1.5 ± 0.5 μM (n=10). 40 μM bicuculline was added to some cell cultures to stabilize activity and verapamil dose response curves were performed in presence of bicuculline, EC50 1.4 ± 0.1 μM (n=9). Statistical analysis showed no significant difference in verapamil EC50s values obtained in presence of bicuculline and hence the data was combined and a standard verapamil EC50 was calculated as 1.4 ± 0.13 μM (n=19). This EC50 was then used to compare verapamil EC50s obtained from neuronal cell cultures with chronic and acute exposures to gentamicin. FC cultures (21- 38 days old) were found to be stable in presence of 2300 μM gentamicin. The recommended concentration of gentamicin for contamination control is 5uL /1 ml medium (108 μM). At this concentration, the verapamil EC50 shifted from 1.4 ± 0.13 μM to 0.9 ± 0.2 μM. Given the limited data points and only two complete CRCs, statistical comparison was not feasible. However, there is a definite trend that shows sensitization of cells to verapamil in presence of gentamicin. The cultures exposed to 108 μM gentamicin for 5 days after seeding showed loss of adhesion and no data could be collected for pharmacological analysis. To conclude, acute gentamicin exposure of neuronal cell cultures causes increased sensitivity to verapamil and chronic or long term exposure to ...
Date: December 2014
Creator: Sawant, Meera
Partner: UNT Libraries

Acute Effects of the Antibiotic Streptomycin on Neural Network Activity and Pharmacological Responses

Description: The purpose of this study is to find out that if antibiotic streptomycin decreases neuronal network activity or affects the pharmacological responses. The experiments in this study were conducted via MEA (multi-electrode array) technology which records neuronal activity from devices that have multiple small electrodes, serve as neural interfaces connecting neurons to electronic circuitry. The result of this study shows that streptomycin lowered the spike production of neuronal network, and also, sensitization was seen when neuronal network pre-exposed to streptomycin.
Access: This item is restricted to UNT Community Members. Login required if off-campus.
Date: December 2014
Creator: Zeng, Wei Rong
Partner: UNT Libraries

Effects of Sertraline Exposure on Fathead Minnow (Pimephales promelas) Steroidogenesis

Description: Sertraline is a selective serotonin reuptake inhibitor (SSRI) that is widely used for the treatment of depression and anxiety. Due to the abundant therapeutic use of sertraline, low levels have been detected in municipal wastewater effluents suggesting that aquatic organisms may be exposed. The purpose of this study was to evaluate the steroidogenic effects of sertraline on larval (FHM) and adult female fathead minnows (FFHM), Pimephales promelas. Larval FHM were exposed to 0.1, 1, and 10 µg/L sertraline for 28 days and analyzed via RT-qPCR for differential expression of 11β-Hydroxysteroid dehydrogenase (11β-HSD), 20β-Hydroxysteroid dehydrogenase (20β-HSD), aromatase (CYP19), and nuclear thyroid receptor alpha (TRα). FFHM were exposed to 3 or 10 µg/L sertraline for 7 days with the brain and ovary excised at exposure termination. Juvenile FHM exposed to 0.1 μg/L sertraline had a significant upregulation of both 20β-HSD and TRα. FFHM exposed to 10 µg/L sertraline had a significant upregulation of 11β-HSD expression in brain tissue, while no steroidogenic changes were observed in the FFHM ovary. Similarly, in FFHM brain tissue, CYP19 and 20β-HSD expression levels were significantly higher in fish exposed to 10µg/L sertraline compared to control. The significance of these findings with respect to survival, growth and reproduction are currently unknown, but represent future research needs.
Date: December 2014
Creator: Carty, Dennis R.
Partner: UNT Libraries

Responses of Cultured Neuronal Networks to the Cannabinoid Mimetic Anandamide

Description: The effects of cannabinoid agonists on spontaneous neuronal network activity were characterized in murine spinal cord and auditory cortical cultures with multichannel extracellular recording using photoetched electrode arrays. Different cultures responded reproducibly with global decreases of spiking and bursting to anandamide and methanandamide, but each agonist showed unique minor effects on network activity. The two tissues responded in a tissue-specific manner. Spontaneous activity in spinal tissue was terminated by 1 μM anandamide and 6.1 μM methanandamide. Cortical activity ceased at 3.5 μM and 2.8 μM respectively. Irreversible cessation of activity was observed beyond 8 μM for both tissues and test substances. Palmitoylethanolamide, demonstrated that CB2 receptors were not present or not responsive. However, the data strongly suggested the presence of CB1 receptors.
Date: May 1998
Creator: Morefield, Samantha I. (Samantha Irene)
Partner: UNT Libraries

In Vitro Studies of Nuclear Changes in Mammalian CNS Neurons Subjected to Rapid Acceleration Impact Injury

Description: An in vitro model of Rapid Acceleration Impact (RAI) Injury was used to study the effects of multiple impact (220 g/impact, 3-5 sec intervals) trauma on cultures of murine CNS cells. Investigations with spinal cord cultures showed that 1) multiple impacts delivered tangential to the plane of cell growth caused neuronal death (12% after 3 impacts to 46% after 10 impacts); 2) multiple impacts delivered normal to the plane of cell growth were much less effective (8% dead after 10 impacts); 3) most neuronal death occurred within 15 minutes after injury 4) morphological changes observed included increased nuclear prominence and somal swelling; and 5) pretreatment with ketamine (0.1mM) reduced cell death from 51 to 14% and reduced somal swelling. Identical studies performed on cortical cultures revealed minimal differences between the two tissues in their response to multiple tangential impacts.
Date: May 1995
Creator: Wolf, Amy
Partner: UNT Libraries

Characterizing Spontaneous Neurophysiological Activity with Measures of Statistical Serial Dependence: a Summary Statistic and an Extension of the Joint Interval Histogram

Description: Two measures which indicate statistical serial dependence were evaluated. The n-dimensional Average Stored Information index (ndASI) is a measure of conditional information, which compares the entropies of higher order conditional distributions to estimate average statistical serial dependence. The generalized ranked joint interval histogram (RJIH-o) is a new nonparametric graphical analysis method. It extends the joint interval histogram by depicting longer interval sequences and can be interpereted precisely analagously to the joint interval histogram. The generalized ranked joint interval histogram correctly represents independence in a Poisson process model and statistical serial dependence in a directionally reinforced Markov model. The generalized ranked joint interval histogram correctly depicts the underlying periodic and strange attractors in a standard map model. Both measures can be used to effectively analyze interspike interval sequences from spontaneous neurophsyiological activity effectively.
Date: August 1994
Creator: Weil, Jon C. (Jon Christopher)
Partner: UNT Libraries

Medial Medulla Networks in Culture: a Multichannel Electrophysiologic and Pharmacological Study

Description: Spontaneously active primary cultures obtained from dissociated embryonic medial medulla tissue were grown on microelectrode arrays for investigating burst patterns and pharmacological responses of respiratory-related neurons. Multichannel burst rates and spike production were used as primary variables for analysis. Pacemaker-like neurons were identified by continued spiking under low Ca++/high Mg++conditions. The number of pacemakers increased with time under synaptic blocking medium. Sensitivity to CO2 levels was found in some neurons. Acetylcholine changed activity in a complex fashion. Curare, atropine and gallamine modified ACh effects. Eserine alone was ineffective, but potentiated ACh-induced responses. Norepinephrine caused channel-specific increases or decreases, whereas dopamine and serotonin had little effect at 30 μM. GABA and glycine stopped most spiking at 70 μM. Developmental changes in glycine sensitivity (increasing with age) were also observed. It is concluded that pacemaker and chemosensitive neurons develop in medial medulla cultures, and that these cultures are pharmacologically histiotypic.
Date: August 1998
Creator: Keefer, Edward W. (Edward Wesley)
Partner: UNT Libraries

Cytotoxicity and Functional Toxicity of Mefloquine and the Search for Protective Compounds

Description: Mefloquine hydrochloride is an antimalarial agent that has been used for the past 40 years. Numerous reports of neurological side effects have recently led the FDA to issue a strong warning regarding long-term neurological effects. This warning lead to the U.S. Army’s Special Forces and other components to discontinue its use in July of 2013. Despite reported adverse side effects, mefloquine remains in circulation and is recommended to travelers going to specific Asian countries. Mefloquine has been used as a treatment for those already infected with the malaria parasite (blood concentrations ranging from 2.1 to 23 µM), and as prophylaxis (blood concentrations averaging 3.8 µM) (Dow 2003). The purpose of this study was to quantify Mefloquine’s toxicity using spontaneously active nerve cell networks growing on microelectrode arrays in vitro and to identify compounds that alleviate or reduce toxic effects. The current literature on mefloquine toxicity is lacking electrophysiological data. These data will contribute to research on the mechanism of adverse side effects associated with mefloquine use. Sequential titration experiments were performed by adding increasing concentrations of mefloquine solution to cultured neurons. Network responses were quantified and reversibility was examined. In each network, activity decreases were normalized as a percent of reference activity yielding a mean IC50 value of 5.97 ± 0.44 (SD) µM (n=6). After total activity loss, no activity was recovered with two successive medium changes. To test for network response desensitization resulting from sequential applications over 5-6 hr periods, one-point titrations at varying concentrations were conducted with fresh networks. These experiments yielded a single concentration response curve with an IC50 value of 2.97 µM. This represents a statistically significant shift (p < 0.0001) to lower concentrations of mefloquine, demonstrating that sequential applications result in network desensitization. After mefloquine exposures, cells were evaluated for irreversible cytotoxic damage. Over a ...
Date: May 2015
Creator: Holmes, Katelyn
Partner: UNT Libraries

Neurotoxicity of the Industrial Solvent 4-Methylcyclohexanemethanol: Involvement of the GABA Receptor

Description: A recent chemical spill of 4-Methylcyclohexanemethanol (4-MCHM) in West Virginia left 300,000 people without water. Officials claimed that this compound is not lethally toxic, but potentially harmful if swallowed or inhaled, and can cause eye and skin irritation. Sittig's Handbook of Toxic and Hazardous Chemical Carcinogens reports high exposures from skin contact or inhalation may cause damage to the heart, liver, kidneys, and lungs, and may result in death. However, no quantitative data seem to exist and no references can be found on neurotoxicity. We have investigated the neurotoxicity of 4-MCHM using mammalian nerve cell networks grown on microelectrode arrays. Network spontaneous activity from multiple units (range 48 – 120 per network) were used as the primary readout. Individual units were followed based on spike waveforms digitized at 40 kHz (Plexon MNAP system). Dose response curves show the effective inhibitory concentration at 50 percent decrease (EC50) to average 27.4 microM SD±6.17. However, in the presence of 40 microM bicuculline, a competitive GABAA antagonist, the EC50 shifts to 70.63uM SD ±4.3; implying that early, low concentration exposures to 4-MCHM involve GABA activation. Initial activity loss occurs without active unit loss (defined as 10 or more template threshold crossing per min), indicating functional interference with spike production. Full recovery has not been seen at concentrations above 130 microM, unless the culture was given bicuculline. Direct exposure to 400uM results in immediate, irreversible loss of spike production, followed by necrosis of glia and neurons.
Date: May 2015
Creator: Gibson, Jason
Partner: UNT Libraries

Neuronal Survival After Dendrite Amputation: Investigation of Injury Current Blockage

Description: After dendrite transection, two primary injury current pathways may acount for cell death: (1) the lesion current at the site of injury and (2) the voltage sensitive calcium channels along the dendrite. Lesions were made with a laser microbeam in mouse spinal monolayer cell cultures. Polylysine was tried as a positively charged "molecular bandage" to block the lesion current. The calcium channel blockers, verapamil and nifedipine, were used to reduce the calcium channel current. Control toxicity curves were obtained for all three compounds. The results show that neither verapamil, nifedipine, nor polylysine (MW: 3,300) protect nerve cells after dendrite amputation 100 ptm from the soma. The data also indicate that these compounds do not slow the process of cell death after such physical trauma.
Date: December 1988
Creator: Shi, Ri Yi
Partner: UNT Libraries

A Multi-Time Scale Learning Mechanism for Neuromimic Processing

Description: Learning and representing and reasoning about temporal relations, particularly causal relations, is a deep problem in artificial intelligence (AI). Learning such representations in the real world is complicated by the fact that phenomena are subject to multiple time scale influences and may operate with a strange attractor dynamic. This dissertation proposes a new computational learning mechanism, the adaptrode, which, used in a neuromimic processing architecture may help to solve some of these problems. The adaptrode is shown to emulate the dynamics of real biological synapses and represents a significant departure from the classical weighted input scheme of conventional artificial neural networks. Indeed the adaptrode is shown, by analysis of the deep structure of real synapses, to have a strong structural correspondence with the latter in terms of multi-time scale biophysical processes. Simulations of an adaptrode-based neuron and a small network of neurons are shown to have the same learning capabilities as invertebrate animals in classical conditioning. Classical conditioning is considered a fundamental learning task in animals. Furthermore, it is subject to temporal ordering constraints that fulfill the criteria of causal relations in natural systems. It may offer clues to the learning of causal relations and mechanisms for causal reasoning. The adaptrode is shown to solve an advanced problem in classical conditioning that addresses the problem of real world dynamics. A network is able to learn multiple, contrary associations that separate in time domains, that is a long-term memory can co-exist with a short-term contrary memory without destroying the former. This solves the problem of how to deal with meaningful transients while maintaining long-term memories. Possible applications of adaptrode-based neural networks are explored and suggestions for future research are made.
Date: August 1994
Creator: Mobus, George E. (George Edward)
Partner: UNT Libraries

Roles of Calcium Ions and Cyclic AMP in Olfactory Transduction

Description: The roles of Ca2 + and cAMP in olfactory transduction were explored using agents which affect calcium channels and second messenger systems. These agents were applied at certain calculated final concentrations onto olfactory epithelia of urethane-anesthetized frogs (Sana PiPlens) by two-sec aerosol spray. During extracellular recording, saturated vapors of isoamyl acetate were delivered every 100 sec in 0.3 sec pulses to produce an electroolfactogram (EOG). Inorganic cations that block inward calcium currents inhibit EOG responses with the following rank order: (La3+) > (Zn2+, Cd2+) > (Al3+, Ca2+, Sr2+) > (Co2+). Application of 7.5 mM La3+ eradicates £0G's, while Ba2+ (which can carry more current that Ca2+) initially produces significant enhancement (F=43.04, p<0.001, df=19). Magnesium ion has no effect on EOG's at 7.5 mM, while 1.5 X 10"4M Ca2+ is significantly inhibitory (F=5.74; p=0.0355; df=12). Control aerosol sprays of distilled water depress EOG's by an average of 5%. The organic calcium channel antagonists diltiazem and verapamil inhibit EOG's by 17% and 36X, respectively, at a concentration of 1.5 X 10~*M. Verapamil produces significant inhibition (F=17.17; p=0.002; df=ll) at 1.5 X 10" 5 M, while the 1,4-dihydropyridine calcium channel antagonists, nicardipine and nifedipine, do not inhibit beyond 1% DMSO controls. Several calmodulin antagonists decrease EOG's, but without correlation to their anti-calmodulin potency. Application of 1.5 X 10"*M chlorpromazine and N-(6-aminohexyl)-5-chloro-l-naphthalenesulfonamide inhibit EOG's by 31% and 27%, respectively, while trifluoperazine inhibits by 23%. Dibutyryl cAMP, a lipophilic mimic of cAMP, produces 54% inhibition at 1.5 X 10" *M. Dibutyryl cGMP, cGMP, cAMP, and adenosine all decrease EOG's by less than 15% compared to distilled water controls. Forskolin, a reversible activator of adenylate cyclase, inhibits EOG's by 57% at 1.5 X 10"5M, which is significant beyond the 1% DMSO controls (F=17.17; p=0.002; df=ll). These data support the hypothesis that Ca2+ participates in olfactory transduction. ...
Date: December 1986
Creator: Winegar, Bruce D. (Bruce David)
Partner: UNT Libraries

Blood Pressure Regulation During Simulated Orthostatism Prior to and Following Endurance Exercise Training

Description: Cardiovascular responses and tolerance to an orthostatic stress were examined in eight men before and after eight months of endurance exercise training. Following training, maximal oxygen consumption and blood volume were increased, and resting heart rate reduced. Orthostatic tolerance was reduced following training in all eight subjects. It was concluded that prolonged endurance training decreased orthostatic tolerance and this decrease in tolerance appeared associated with attenuated baroreflex sensitivity and alterations in autonomic balance secondary to an increased parasympathetic tone noted with training.
Date: May 1992
Creator: Stevens, Glen Harold John
Partner: UNT Libraries

Chemically Active Odorants as Olfactory Probes

Description: The initial step in odor recognition by the nose is the binding of odorant molecules to receptor sites embedded in the dendritic membranes of olfactory receptor cells. Despite considerable interest and experimentation into the nature of these receptor sites, little is known of their specificity to different types of odorant molecules. This lack of knowledge partially stems from the fact that the nature of receptor proteins is most effectively studied when specific and irreversible inhibitors are available for use as chemical probes, yet no such agents have been discovered for use in the olfactory system. A series of alkylating agents and other chemically active odorants were tested to determine whether they might react with specific odorant receptors and modify olfactory responses. Electroolfactogram (EOG) recordings were obtained before, during, and after treatment of the olfactory mucosae of grass frogs (Rana pipiens) with a chemically active odorant.
Date: May 1982
Creator: Criswell, Darrell W. (Darrell Wayne)
Partner: UNT Libraries