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Full-Text Articles in Neurosciences

Role Of Membrane Gm1 On Early Neuronal Membrane Actions Of Aβ During Onset Of Alzheimer's Disease, E. J. Fernandez-Perez, Fernando Sepulveda, Robert W. Peoples, Luis G. Aguayo Dec 2017

Role Of Membrane Gm1 On Early Neuronal Membrane Actions Of Aβ During Onset Of Alzheimer's Disease, E. J. Fernandez-Perez, Fernando Sepulveda, Robert W. Peoples, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

The ability of beta-amyloid peptide (Aβ) to disrupt the plasma membrane through formation of pores and membrane breakage has been previously described. However, the molecular determinants for these effects are largely unknown. In this study, we examined if the association and subsequent membrane perforation induced by Aβ was dependent on GM1levels. Pretreatment of hippocampal neurons with D-PDMP decreased GM1 and Aβ clustering at the membrane (Aβ fluorescent-punctas/20 μm, control = 16.2 ± 1.1 vs. D-PDMP = 6.4 ± 0.4, p < 0.001). Interestingly, membrane perforation with Aβ occurred with a slower time course when the GM1 content was diminished (time to establish perforated configuration (TEPC) (min): control = 7.8 ± 2 vs. low GM1 = 12.1 ± 0.5, p < 0.01), suggesting that the presence of GM1 in the membrane can modulate the distribution and the membrane perforation by Aβ. On the other hand, increasing GM1 facilitated the membrane perforation (TEPC: control = 7.8 ± 2 vs. GM1 = 6.2 ± 1 min, p < 0.05). Additionally, using Cholera Toxin Subunit-B (CTB) to block the interaction of Aβ with GM1 attenuated membrane perforation significantly. Furthermore, …


Corticosterone Regulates Both Naturally Occurring And Cocaine‐Induced Dopamine Signaling By Selectively Decreasing Dopamine Uptake, Daniel S. Wheeler, Amanda L. Ebben, Beliz Kurtoglu, Marissa E. Lovell, Austin T. Bohn, Isabella A. Jasek, David A. Baker, John R. Mantsch, Paul J. Gasser, Robert A. Wheeler Nov 2017

Corticosterone Regulates Both Naturally Occurring And Cocaine‐Induced Dopamine Signaling By Selectively Decreasing Dopamine Uptake, Daniel S. Wheeler, Amanda L. Ebben, Beliz Kurtoglu, Marissa E. Lovell, Austin T. Bohn, Isabella A. Jasek, David A. Baker, John R. Mantsch, Paul J. Gasser, Robert A. Wheeler

Biomedical Sciences Faculty Research and Publications

Stressful and aversive events promote maladaptive reward‐seeking behaviors such as drug addiction by acting, in part, on the mesolimbic dopamine system. Using animal models, data from our laboratory and others show that stress and cocaine can interact to produce a synergistic effect on reward circuitry. This effect is also observed when the stress hormone corticosterone is administered directly into the nucleus accumbens (NAc), indicating that glucocorticoids act locally in dopamine terminal regions to enhance cocaine's effects on dopamine signaling. However, prior studies in behaving animals have not provided mechanistic insight. Using fast‐scan cyclic voltammetry, we examined the effect of systemic …


Extending The Family: Roles For Uptake2 Transporters In Regulation Of Monoaminergic Signaling, Paul J. Gasser, Lynette C. Daws Oct 2017

Extending The Family: Roles For Uptake2 Transporters In Regulation Of Monoaminergic Signaling, Paul J. Gasser, Lynette C. Daws

Biomedical Sciences Faculty Research and Publications

No abstract provided.


Editorial For The Special Issue: Monoamine Transporters In Health And Disease, Paul J. Gasser, Lynette C. Daws Oct 2017

Editorial For The Special Issue: Monoamine Transporters In Health And Disease, Paul J. Gasser, Lynette C. Daws

Biomedical Sciences Faculty Research and Publications

No abstract provided.


Organic Cation Transporter 3 (Oct3) Is Localized To Intracellular And Surface Membranes In Select Glial And Neuronal Cells Within The Basolateral Amygdaloid Complex Of Both Rats And Mice, Paul J. Gasser, Matthew M. Hurley, June Chan, Virginia M. Pickel May 2017

Organic Cation Transporter 3 (Oct3) Is Localized To Intracellular And Surface Membranes In Select Glial And Neuronal Cells Within The Basolateral Amygdaloid Complex Of Both Rats And Mice, Paul J. Gasser, Matthew M. Hurley, June Chan, Virginia M. Pickel

Biomedical Sciences Faculty Research and Publications

Organic cation transporter 3 (OCT3) is a high-capacity, low-affinity transporter that mediates corticosterone-sensitive uptake of monoamines including norepinephrine, epinephrine, dopamine, histamine and serotonin. OCT3 is expressed widely throughout the amygdaloid complex and other brain regions where monoamines are key regulators of emotional behaviors affected by stress. However, assessing the contribution of OCT3 to the regulation of monoaminergic neurotransmission and monoamine-dependent regulation of behavior requires fundamental information about the subcellular distribution of OCT3 expression. We used immunofluorescence and immuno-electron microscopy to examine the cellular and subcellular distribution of the transporter in the basolateral amygdaloid complex of the rat and mouse brain. …


The Application Of Crispr Technology To High Content Screening In Primary Neurons, Ben L. Callif, Brian Maunze, Nick L. Krueger, Matthew T. Simpson, Murray G. Blackmore Apr 2017

The Application Of Crispr Technology To High Content Screening In Primary Neurons, Ben L. Callif, Brian Maunze, Nick L. Krueger, Matthew T. Simpson, Murray G. Blackmore

Biomedical Sciences Faculty Research and Publications

Axon growth is coordinated by multiple interacting proteins that remain incompletely characterized. High content screening (HCS), in which manipulation of candidate genes is combined with rapid image analysis of phenotypic effects, has emerged as a powerful technique to identify key regulators of axon outgrowth. Here we explore the utility of a genome editing approach referred to as CRISPR (Clustered Regularly Interspersed Palindromic Repeats) for knockout screening in primary neurons. In the CRISPR approach a DNA-cleaving Cas enzyme is guided to genomic target sequences by user-created guide RNA (sgRNA), where it initiates a double-stranded break that ultimately results in frameshift mutation …


Combined Chondroitinase And Klf7 Expression Reduce Net Retraction Of Sensory And Cst Axons From Sites Of Spinal Injury, Zimei Wang, Kristen N. Winsor, Evan Hess, Murray G. Blackmore, Christopher Nienhaus Mar 2017

Combined Chondroitinase And Klf7 Expression Reduce Net Retraction Of Sensory And Cst Axons From Sites Of Spinal Injury, Zimei Wang, Kristen N. Winsor, Evan Hess, Murray G. Blackmore, Christopher Nienhaus

Biomedical Sciences Faculty Research and Publications

Axon regeneration in the central nervous system is limited both by inhibitory extracellular cues and by an intrinsically low capacity for axon growth in some CNS populations. Chondroitin sulfate proteoglycans (CSPGs) are well-studied inhibitors of axon growth in the CNS, and degradation of CSPGs by chondroitinase has been shown to improve the extension of injured axons. Alternatively, axon growth can be improved by targeting the neuron-intrinsic growth capacity through forced expression of regeneration-associated transcription factors. For example, a transcriptionally active chimera of Krüppel-like Factor 7 (KLF7) and a VP16 domain improves axon growth when expressed in corticospinal tract neurons. Here …


Corticosterone Potentiation Of Cocaine-Induced Reinstatement Of Conditioned Place Preference In Mice Is Mediated By Blockade Of The Organic Cation Transporter 3, Jayme R. Mcreynolds, Analisa Taylor, Oliver Vranjkovic, Terra Ambrosius, Olivia Derricks, Brittany Nino, Beliz Kurtoglu, Robert A. Wheeler, David A. Baker, Paul J. Gasser, John R. Mantsch Feb 2017

Corticosterone Potentiation Of Cocaine-Induced Reinstatement Of Conditioned Place Preference In Mice Is Mediated By Blockade Of The Organic Cation Transporter 3, Jayme R. Mcreynolds, Analisa Taylor, Oliver Vranjkovic, Terra Ambrosius, Olivia Derricks, Brittany Nino, Beliz Kurtoglu, Robert A. Wheeler, David A. Baker, Paul J. Gasser, John R. Mantsch

Biomedical Sciences Faculty Research and Publications

The mechanisms by which stressful life events increase the risk of relapse in recovering cocaine addicts are not well understood. We previously reported that stress, via elevated corticosterone, potentiates cocaine-primed reinstatement of cocaine seeking following self-administration in rats and that this potentiation appears to involve corticosterone-induced blockade of dopamine clearance via the organic cation transporter 3 (OCT3). In the present study, we use a conditioned place preference/reinstatement paradigm in mice to directly test the hypothesis that corticosterone potentiates cocaine-primed reinstatement by blockade of OCT3. Consistent with our findings following self-administration in rats, pretreatment of male C57/BL6 mice with corticosterone (using …


Long Days Enhance Recognition Memory And Increase Insulin-Like Growth Factor 2 In The Hippocampus, Adriano Dellapolla, Ian Kloehn, Harshida Pancholi, Ben L. Callif, David Wertz, Kayla Rohr, Matthew M. Hurley, Kimberly Baker, Samer Hattar, Marieke R. Gilmartin, Jennifer A. Evans Jan 2017

Long Days Enhance Recognition Memory And Increase Insulin-Like Growth Factor 2 In The Hippocampus, Adriano Dellapolla, Ian Kloehn, Harshida Pancholi, Ben L. Callif, David Wertz, Kayla Rohr, Matthew M. Hurley, Kimberly Baker, Samer Hattar, Marieke R. Gilmartin, Jennifer A. Evans

Biomedical Sciences Faculty Research and Publications

Light improves cognitive function in humans; however, the neurobiological mechanisms underlying positive effects of light remain unclear. One obstacle is that most rodent models have employed lighting conditions that cause cognitive deficits rather than improvements. Here we have developed a mouse model where light improves cognitive function, which provides insight into mechanisms underlying positive effects of light. To increase light exposure without eliminating daily rhythms, we exposed mice to either a standard photoperiod or a long day photoperiod. Long days enhanced long-term recognition memory, and this effect was abolished by loss of the photopigment melanopsin. Further, long days markedly altered …