Systemic morphine treatment induces changes in firing patterns and responses of nociceptive afferent fibers in mouse glabrous skin.

Patients receiving opioids for pain may experience decreased effectiveness of the drug and even abnormal pain sensitivity-hyperalgesia and/or allodynia. We hypothesized that peripheral nociceptor hyperexcitability contributes to opioid-induced hyperalgesia and tested this using an in vitro mouse glabrous skin-nerve preparation. Mice were injected intraperitoneally with escalating doses of morphine (5, 8, 10, 15 mg/kg) or saline every 12 hours for 48 hours and killed approximately 12 hours after the last injection.

Topical metal chelation therapy ameliorates oxidation-induced toxicity in diabetic cataract.

Oxidative stress plays a critical role in cataractogenesis, the leading cause of blindness worldwide. Since transition metals generate reactive oxygen species (ROS) formation, metal chelation therapy has been proposed for treatment of cataracts. However, the effectiveness of most chelators is limited by low tissue penetrability.

Intermediate- and long-term recognition memory deficits in Tg2576 mice are reversed with acute calcineurin inhibition.

The Tg2576 transgenic mouse is an extensively characterized animal model for Alzheimer's disease (AD). Similar to AD, these mice suffer from progressive decline in several forms of declarative memory including contextual fear conditioning and novel object recognition (NOR). Recent work on this and other AD animal models suggests that initial cognitive deficits are due to synaptic dysfunction that, with the correct intervention, are fully treatable.

Collapsin response mediator protein-2 hyperphosphorylation is an early event in Alzheimer's disease progression.

Collapsin response mediator protein 2 (CRMP2) is an abundant brain-enriched protein that can regulate microtubule assembly in neurons. This function of CRMP2 is regulated by phosphorylation by glycogen synthase kinase 3 (GSK3) and cyclin-dependent kinase 5 (Cdk5). Here, using novel phosphospecific antibodies, we demonstrate that phosphorylation of CRMP2 at Ser522 (Cdk5-mediated) is increased in Alzheimer's disease (AD) brain, while CRMP2 expression and phosphorylation of the closely related isoform CRMP4 are not altered.

Acute inhibition of calcineurin restores associative learning and memory in Tg2576 APP transgenic mice.

Misfolded amyloid beta peptide (Abeta) is a pathological hallmark of Alzheimer's disease (AD), a neurodegenerative illness characterized by cognitive deficits and neuronal loss. Transgenic mouse models of Abeta over-production indicate that Abeta-induced cognitive deficits occur in the absence of overt neuronal death, suggesting that while extensive neuronal death may be associated with later stages of the human disease, subtle physiological changes may underlie initial cognitive deficits. Therefore, identifying signaling elements involved in those Abeta-induced cognitive impairments that occur prior to loss of neurons may reveal new potential pharmacological targets.

Antipsychotic drug interactions with specific [3H]ketanserin binding sites in membrane fragments derived from human prefrontal cortex and human amygdala.

Two regions of the brain potentially significant for psychopathology in schizophrenia are the prefrontal cortex and the amygdala. Antipsychotic compounds bind at serotonin receptors in human prefrontal cortex. We hypothesized that the serotoninergic antagonist [3H]ketanserin would label similar sets of binding sites in these two brain regions.

Interleukin-6 alters sleep of rats.

Although it is well established that the cytokines tumor necrosis factor (TNF) and interleukin (IL)-1 regulate sleep, there is no direct evidence implicating IL-6 in the regulation/modulation of sleep. We tested the hypotheses that central administration of rat recombinant IL-6 increases non-rapid eye movements (NREM) sleep of rats, and that central administration of anti-IL-6 antibodies reduces NREM sleep. Effective doses of IL-6 (100 and 500 ng) initially enhance NREM sleep, after which NREM sleep may be suppressed.