A Modified Two-Way Active Avoidance Test for Combined Contextual and Auditory Instrumental Conditioning.

Available two-way active avoidance paradigms do not provide contextual testing, likely due to challenges in performing repetitive trials of context exposure. To incorporate contextual conditioning in the two-way shuttle box, we contextually modified one of the chambers of a standard two-chamber rat shuttle box with visual cues consisting of objects and black and white stripe patterns. During the 5 training days, electrical foot shocks were delivered every 10 s in the contextually modified chamber but were signaled by a tone in the plain chamber. Shuttling between chambers prevented an incoming foot shock (avoidance) or aborted an ongoing one (escape). During contextual retention testing, rats were allowed to freely roam in the box. During auditory retention testing, visual cues were removed, and tone-signaled shocks were delivered in both chambers. Avoidance gradually replaced escape or freezing behaviors reaching 80% on the last training day in both chambers. Rats spent twice more time in the plain chamber during contextual retention testing and had 90% avoidance rates during auditory retention testing. Our modified test successfully assesses both auditory and contextual two-way active avoidance. By efficiently expanding its array of outcomes, our novel test will complement standard two-way active avoidance in mechanistic studies and will improve its applications in translational research.

Gender-biased kidney damage in mice following exposure to tobacco cigarette smoke: More protection in premenopausal females.

Multiple clinical studies documented renal damage in chronic cigarette smokers (CS) irrespective of their age and gender. Premenopausal female smokers are known to exert a certain cardiovascular and renal protection with undefined mechanisms. Given the multiple demographic variables within clinical studies, this experimental study was designed to be the first to assess whether gender-biased CS-induced kidney damage truly exists between premenopausal female and age-matched C57Bl6J male mice when compared to their relative control groups. Following 6 weeks of CS exposure, cardiac function, inflammatory marker production, fibrosis formation, total and glomerular ROS levels, and glomerulotubular homeostasis were assessed in both genders. Although both CS-exposed male and female mice exhibited comparable ROS fold change relative to their respective control groups, CS-exposed male mice showed a more pronounced fibrotic deposition, inflammation, and glomerulotubular damage profile. However, the protection observed in CS-exposed female group was not absolute. CS-exposed female mice exhibited a significant increase in fibrosis, ROS production, and glomerulotubular alteration but with a pronounced anti-inflammatory profile when compared to their relative control groups. Although both CS-exposed genders presented with altered glomerulotubular homeostasis, the alteration phenotype between genders was different. CS-exposed males showed a significant decrease in Bowman's space along with reduced tubular diameter consistent with an endocrinization pattern of chronic tubular atrophy, suggestive of an advanced stage of glomerulotubular damage. CS-exposed female group, on the other hand, displayed glomerular hypertrophy with a mild tubular dilatation profile suggestive of an early stage of glomerulotubular damage that generally precedes collapse. In conclusion, both genders are prone to CS-induced kidney damage with pronounced female protection due to a milder damage slope.

Rodent Models of Methamphetamine Misuse: Mechanisms of Methamphetamine Action and Comparison of Different Rodent Paradigms.

Methamphetamine (METH) is among the most widely used illegal forms of amphetamine. Whether it is injected, snorted, or smoked, METH is a highly addictive substance that affects both peripheral and central nervous system actions. METH use ranges from episodes of binge to chronic use. To investigate METH effects, several animal models have been developed and described to model the various patterns of human METH use. In this work, we examine the molecular, cellular, and structural mechanisms of METH use. Then, we describe the different animal models of METH misuse. Next, we discuss, in details, the acute exposure model which assesses the immediate effects of METH on the brain and the chronic exposure model which best describes the more common long-term consequences of METH use observed in humans. Finally, we tackle the effects and consequences of each paradigm and focus on METH-induced neurotoxic effects and the behavioral changes attributed to each of the described paradigms.

Glycosylation Changes in Brain Cancer.

Protein glycosylation is a posttranslational modification that affects more than half of all known proteins. Glycans covalently bound to biomolecules modulate their functions by both direct interactions, such as the recognition of glycan structures by binding partners, and indirect mechanisms that contribute to the control of protein conformation, stability, and turnover. The focus of this Review is the discussion of aberrant glycosylation related to brain cancer. Altered sialylation and fucosylation of N- and O-glycans play a role in the development and progression of brain cancer. Additionally, aberrant O-glycan expression has been implicated in brain cancer. This Review also addresses the clinical potential and applications of aberrant glycosylation for the detection and treatment of brain cancer. The viable roles glycans may play in the development of brain cancer therapeutics are addressed as well as cancer-glycoproteomics and personalized medicine. Glycoprotein alterations are considered as a hallmark of cancer while high expression in body fluids represents an opportunity for cancer assessment.