Leptin signaling has received considerable attention in the Alzheimer disease (AD) field. Within the past decade, the peptide hormone has been demonstrated to attenuate tau hyperphosphorylation in neuronal cells and to be modulated by amyloid-β. Moreover, a role in neuroprotection and neurogenesis within the hippocampus has been shown in animal models. To further characterize the association between leptin signaling and vulnerable regions in AD, we assessed the profile of leptin and the leptin receptor in AD and control patients. We analyzed leptin levels in cerebrospinal fluid (CSF), and the concentration and localization of leptin and leptin receptor in the hippocampus. Significant elevations in leptin levels in both CSF and hippocampal tissue of AD patients, compared to age-matched control cases, indicate a physiological upregulation of leptin in AD. However, the level of leptin receptor mRNA decreased in AD brain and the leptin receptor protein was localized to neurofibrillary tangles, suggesting a severe discontinuity in the leptin signaling pathway. Collectively, our results suggest that leptin resistance in the hippocampus may play a role in the characteristic changes associated with the disease. These findings are the first to demonstrate such dysregulated leptin-signaling circuitry and provide novel insights into the possible role of aberrant leptin signaling in AD.

Objective: To present recommendations for the prevention, recognition, and treatment of environmental cold injuries.Background: Individuals engaged in sport-related or workrelated physical activity in cold, wet, or windy conditions are at risk for environmental cold injuries. An understanding of the physiology and pathophysiology, risk management, recognition, and immediate care of environmental cold injuries is an essential skill for certified athletic trainers and other health care providers working with individuals at risk.Recommendations: These recommendations are intended to provide certified athletic trainers and others participating in athletic health care with the specific knowledge and problem-solving skills needed to address environmental cold injuries. Each recommendation has been graded (A, B, or C) according to the Strength of Recommendation Taxonomy criterion scale.

Tryptophan metabolism, through the kynurenine pathway (KP), produces neurotoxic intermediates that are implicated in the pathogenesis of Alzheimer disease (AD). In particular, oxidative stress via 3-hydroxykynurenine (3-HK) and its cleaved product 3-hydroxyanthranilic acid (3-HAA) significantly damages neuronal tissue and may potentially contribute to a cycle of neurodegeneration through consequent amyloid-β accumulation, glial activation, and upregulation of the KP. To determine the role of the KP in eliciting and continuing oxidative stress within AD brain, we used immunocytochemical methods to show elevated levels of 3-HK modifications and the upstream, ratelimiting enzyme indoleamine 2,3-dioxygenase (IDO-1) in AD brain when compared to controls. Importantly, the association of IDO-1 with senile plaques was confirmed, and for the first time, IDO-1 was shown to be specifically localized in conjunction with neurofibrillary tangles. As senile plaques and neurofibrillary tangles are the pathological hallmarks of AD, our study provides further evidence that the KP is involved with the destructive neurodegenerative pathway of AD.

J. Neurochem. (2012) 121, 672–679. Abstract Fragile X syndrome (FXS) is a developmental disorder caused by the loss of Fragile X Mental Retardation 1 (FMR1) gene function because of a CGG repeat expansion (> 200 repeats) in the gene. The molecular mechanism(s) linking loss of FMR1 function to the molecular pathology and cognitive/behavioral disability remain unclear. Given the critical role of extracellular signal‐regulated kinase (ERK) in synaptic plasticity and neurodevelopment, a number of recent studies have investigated ERK phosphorylation under basal conditions or upon mGluR‐induction using neuronal and peripheral tissues from Fmr1 knockout mice and peripheral tissues from FXS patients. However, these reports have presented conflicting results. The current study is the first to focus on the levels of ERK phosphorylation in brain tissue from human FXS patients. In both human brain tissue and brain tissue from Fmr1 knockout mice there was significantly increased phosphorylation of MEK1/2 and ERK. Indeed, treating Fmr1 knockout mice with the MEK1/2 inhibitor SL327 abrogated audiogenic seizure activity, a feature of the Fmr1 knockout mice that replicates the symptom in patients with FXS. These findings suggest that activation of the ERK pathway results in some cardinal cognitive and clinical features in FXS patients and likely have profound translational implications.