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Sex Differences In Metabolic Phenotype And Hypothalamic Inflammation In The 3xtg-Ad Mouse Model Of Alzheimer's Disease., Lisa S. Robison, Olivia J. Gannon, Abigail E. Salinero, Charly Abi-Ghanem, Richard D. Kelly, David A. Riccio, Febronia M. Mansour, Kristen L. Zuloaga Aug 2023

Sex Differences In Metabolic Phenotype And Hypothalamic Inflammation In The 3xtg-Ad Mouse Model Of Alzheimer's Disease., Lisa S. Robison, Olivia J. Gannon, Abigail E. Salinero, Charly Abi-Ghanem, Richard D. Kelly, David A. Riccio, Febronia M. Mansour, Kristen L. Zuloaga

Faculty Articles

BACKGROUND: Alzheimer's disease (AD) is notably associated with cognitive decline resulting from impaired function of hippocampal and cortical areas; however, several other domains and corresponding brain regions are affected. One such brain region is the hypothalamus, shown to atrophy and develop amyloid and tau pathology in AD patients. The hypothalamus controls several functions necessary for survival, including energy and glucose homeostasis. Changes in appetite and body weight are common in AD, often seen several years prior to the onset of cognitive symptoms. Therefore, altered metabolic processes may serve as a biomarker for AD, as well as a target for treatment, …


Loss Of Resistance To Angiotensin Ii-Induced Hypertension In The Jackson Laboratory Recombination-Activating Gene Null Mouse On The C57bl/6j Background, Hong Ji, Amrita V Pai, Crystal A West, Xie Wu, Robert Charles Speth, Kathryn Sandberg Jun 2017

Loss Of Resistance To Angiotensin Ii-Induced Hypertension In The Jackson Laboratory Recombination-Activating Gene Null Mouse On The C57bl/6j Background, Hong Ji, Amrita V Pai, Crystal A West, Xie Wu, Robert Charles Speth, Kathryn Sandberg

Faculty Articles

Resistance to angiotensin II (Ang II)–induced hypertension in T-cell–deficient male mice with a targeted mutation in the recombination-activating gene-1 (Rag1) on the C57BL/6J background (B6.Rag1−/−-M), which was reported by 5 independent laboratories including ours before 2015, has been lost. In mice purchased from Jackson Laboratory in 2015 and 2016, the time course and magnitude increase in mean arterial pressure induced by 2 weeks of Ang II infusion at 490 ng/kg per minute was identical between B6.Rag1−/−-M and male wild-type littermates. Moreover, there were no differences in the time course or magnitude increase …


An In Vitro And In Vivo Investigation Of Bivalent Ligands That Display Preferential Binding And Functional Activity For Different Melanocortin Receptor Homodimers, Cody J Lensing, Katie T Freeman, Sathya M Schnell, Danielle N Adank, Robert Charles Speth, Carrie Haskell-Luevano Apr 2016

An In Vitro And In Vivo Investigation Of Bivalent Ligands That Display Preferential Binding And Functional Activity For Different Melanocortin Receptor Homodimers, Cody J Lensing, Katie T Freeman, Sathya M Schnell, Danielle N Adank, Robert Charles Speth, Carrie Haskell-Luevano

Faculty Articles

Pharmacological probes for the melanocortin receptors have been utilized for studying various disease states including cancer, sexual function disorders, Alzheimer's disease, social disorders, cachexia, and obesity. This study focused on the design and synthesis of bivalent ligands to target melanocortin receptor homodimers. Lead ligands increased binding affinity by 14- to 25-fold and increased cAMP signaling potency by 3- to 5-fold compared to their monovalent counterparts. Unexpectedly, different bivalent ligands showed preferences for particular melanocortin receptor subtypes depending on the linker that connected the binding scaffolds, suggesting structural differences between the various dimer subtypes. Homobivalent compound 12 possessed a functional profile …


Selective C1 Lesioning Slightly Decreases Angiotensin Ii Type I Receptor Expression In The Rat Rostral Ventrolateral Medulla (Rvlm)., Erick A Bourassa, Kristen A Stedenfeld, Alan F Sved, Robert Charles Speth Oct 2015

Selective C1 Lesioning Slightly Decreases Angiotensin Ii Type I Receptor Expression In The Rat Rostral Ventrolateral Medulla (Rvlm)., Erick A Bourassa, Kristen A Stedenfeld, Alan F Sved, Robert Charles Speth

Faculty Articles

Cardiovascular homeostasis is regulated in large part by the rostral ventrolateral medulla (RVLM) in mammals. Projections from the RVLM to the intermediolateral column of the thoracolumbar spinal cord innervate preganglionic neurons of the sympathetic nervous system causing elevation of blood pressure and heart rate. A large proportion, but not all, of the neurons in the RVLM contain the enzymes necessary for the production of epinephrine and are identified as the C1 cell group. Angiotensin II (Ang II) activates the RVLM acting upon AT1 receptors. To assess the proportion of AT1 receptors that are located on C1 neurons in the rat …