Lifelong Glutathione Deficiency in Mice Increased Lifespan and Delayed Age-Related Motor Declines.

Glutathione (GSH) is a crucial redox scavenger, essential for maintaining cellular redox balance. This study explores the long-term effects of chronic GSH deficiency on lifespan, motor function, cognitive performance, redox status and inflammation. GCLM mice, with a 70-90% reduction in GSH levels, were compared to GCLM controls across their lifespan (5, 10 and 20 months).

A High-Throughput Workflow to Analyze Sequence-Conformation Relationships and Explore Hydrophobic Patterning in Disordered Peptoids.

Understanding how a macromolecule's primary sequence governs its conformational landscape is crucial for elucidating its function, yet these design principles are still emerging for macromolecules with intrinsic disorder. Herein, we introduce a high-throughput workflow that implements a practical colorimetric conformational assay, introduces a semi-automated sequencing protocol using MALDI-MS/MS, and develops a generalizable sequence-structure algorithm. Using a model system of 20mer peptidomimetics containing polar glycine and hydrophobic -butylglycine residues, we identified nine classifications of conformational disorder and isolated 122 unique sequences across varied compositions and conformations.

Immune Potentiation of PLGA Controlled-Release Vaccines for Improved Immunological Outcomes.

With the emergence of SARS-CoV-2 and the continued emergence of new infectious diseases, there is a need to improve and expand current vaccine technology. Controlled-release subunit vaccines provide several benefits over current vaccines on the market, including the use of less antigen and fewer boost doses. Previously, our group reported molecules that alter NF-κB signaling improved the vaccine's performance and improved adjuvant-related tolerability.

Hyperbaric oxygen alleviates selective domains of cognitive and motor deficits in female 5xFAD mice.

Treatment of Alzheimer's disease (AD) has been limited to managing of symptoms or anti-amyloid therapy with limited results and uncertainty. Seeking out new therapies that can reverse the effects of this devastating disease is important. Hyperbaric oxygen (HBO) therapy could be such a candidate as it has been shown to improve brain function in certain neurological conditions.

Effects of chronic methamphetamine exposure on rewarding behavior and neurodegeneration markers in adult mice.

Recreational and medical use of stimulants among young adults have gained popularity in the United States over the last decade and their use may increase vulnerability to brain biochemical changes and addictive behaviors. The long-term effects of chronic stimulant exposure in later adulthood have not been fully elucidated.Our study investigated whether chronic exposure to methamphetamine (METH), at a dose designed to emulate human therapeutic dosing for ADHD, would promote biochemical alterations and affect sensitivity to the rewarding effects of subsequent METH dosing.

Sex differences in neurobehavioral consequences of methamphetamine exposure in adult mice.

Rationale: Recreational and medical use of stimulants is increasing, and their use may increase susceptibility to aging and promote neurobehavioral impairments. The long-term consequences of these psychostimulants and how they interact with age have not been fully studied.

Objectives: Our study investigated whether chronic exposure to the prototypical psychostimulant, methamphetamine (METH), at doses designed to emulate human therapeutic dosing, would confer a pro-oxidizing redox shift promoting long-lasting neurobehavioral impairments.

Frustrative nonreward and cannabinoid receptors: Chronic (but not acute) WIN 55,212-2 treatment increased resistance to change in two reward downshift tasks.

Assessing the role of cannabinoid (CB) receptors in behavior is relevant given the trend toward the legalization of medicinal and recreational marijuana. The present research aims at bridging a gap in our understanding of CB-receptor function in animal models of frustrative nonreward. These experiments were designed to (1) determine the effects of chronic administration of the nonselective CB1-receptor agonist WIN 55,212-2 (WIN) on reward downshift in rats and (2) determine whether the effects of chronic WIN were reducible to acute effects.

Neurodegenerative Disease: Roles for Sex, Hormones, and Oxidative Stress.

Neurodegenerative diseases cause severe impairments in cognitive and motor function. With an increasing aging population and the onset of these diseases between 50 and 70 years, the consequences are bound to be devastating. While age and longevity are the main risk factors for neurodegenerative diseases, sex is also an important risk factor.

Pharmacologic fibroblast reprogramming into photoreceptors restores vision.

Photoreceptor loss is the final common endpoint in most retinopathies that lead to irreversible blindness, and there are no effective treatments to restore vision. Chemical reprogramming of fibroblasts offers an opportunity to reverse vision loss; however, the generation of sensory neuronal subtypes such as photoreceptors remains a challenge. Here we report that the administration of a set of five small molecules can chemically induce the transformation of fibroblasts into rod photoreceptor-like cells.

Gait Analyses in Mice: Effects of Age and Glutathione Deficiency.

Minor changes (~0.1 m/s) in human gait speed are predictive of various measures of decline and can be used to identify at-risk individuals prior to further decline. These associations are possible due to an abundance of human clinical research.