Cellular registration without behavioral recall of olfactory sensory input under general anesthesia.

BACKGROUND: Previous studies suggest that sensory information is "received" but not "perceived" under general anesthesia. Whether and to what extent the brain continues to process sensory inputs in a drug-induced unconscious state remain unclear. METHODS: One hundred seven rats were randomly assigned to 12 different anesthesia and odor exposure paradigms. The immunoreactivities of the immediate early gene products c-Fos and Egr1 as neural activity markers were combined with behavioral tests to assess the integrity and relationship of cellular and behavioral responsiveness to olfactory stimuli under a surgical plane of ketamine-xylazine general anesthesia. RESULTS: The olfactory sensory processing centers could distinguish the presence or absence of experimental odorants even when animals were fully anesthetized. In the anesthetized state, the c-Fos immunoreactivity in the higher olfactory cortices revealed a difference between novel and familiar odorants similar to that seen in the awake state, suggesting that the anesthetized brain functions beyond simply receiving external stimulation. Reexposing animals to odorants previously experienced only under anesthesia resulted in c-Fos immunoreactivity, which was similar to that elicited by familiar odorants, indicating that previous registration had occurred in the anesthetized brain. Despite the "cellular memory," however, odor discrimination and forced-choice odor-recognition tests showed absence of behavioral recall of the registered sensations, except for a longer latency in odor recognition tests. CONCLUSIONS: Histologically distinguishable registration of sensory processing continues to occur at the cellular level under ketamine-xylazine general anesthesia despite the absence of behavioral recognition, consistent with the notion that general anesthesia causes disintegration of information processing without completely blocking cellular communications.

Beta1-integrin signaling is essential for lens fiber survival.

Integrins have been proposed to play a major role in lens morphogenesis. To determine the role of beta1-integrin and its down-stream signaling partner, integrin linked kinase (ILK), in lens morphogenesis, eyes of WT mice and mice with a nestin-linked conditional knockout of beta1-integrin or ILK were analyzed for defects in lens development. Mice, lacking the genes encoding the beta1-integrin subunit (Itgb1) or ILK (Ilk), showed a perinatal degeneration of the lens. Early signs of lens degeneration included vacuolization, random distribution of lens cell nuclei, disrupted fiber morphology and attenuation and separation of the lens capsule. The phenotype became progressively more severe during the first postnatal week eventually leading to the complete loss of the lens. A more severe phenotype was observed in ILK mutants at similar stages. Eyes from embryonic day 13 beta1-integrin-mutant embryos showed no obvious signs of lens degeneration, indicating that mutant lens develops normally until peri-recombination. Our findings suggest that beta1-integrins and ILK cooperate to control lens cell survival and link lens fibers to the surrounding extracellular matrix. The assembly and integrity of the lens capsule also appears to be reliant on integrin signaling within lens fibers. Extrapolation of these results indicates a novel role of integrins in lens cell-cell adhesions as well as a potential role in the pathogenesis of congenital cataracts.

3-aminobenzamide prevents restraint-evoked immunocompromise.

Chronic stressors compromise immune function, which may affect disease state in rats and mice. Although the molecular mechanism(s) underlying the link between psychological stressors and physiological responses remain elusive, one putative mechanism is oxidative stress. DNA damage activates poly(ADP-ribose) polymerase (PARP), a nuclear enzyme that participates in DNA repair; if DNA damage is extensive, however, then PARP becomes cytotoxic. Because PARP-1-/- transgenic mice are resistant to chronic stress-induced immunocompromise, we tested the hypothesis that pre-restraint administration of 3-aminobenzamide (3-AB), a PARP inhibitor, would prevent restraint-evoked suppression of antibody production to the novel protein, keyhole limpet hemocyanin (KLH). Mice were physically restrained for 3 h daily for 14 consecutive days, then immunized with KLH. Daily restraint continued for an additional 21 days and anti-KLH IgG production was assessed. Mice exposed to repeated restraint reduced concentrations of anti-KLH IgG, whereas, mice treated with 3-AB (0.5, 5.0, or 20.0 mg/kg) prior to each bout of restraint displayed anti-KLH IgG concentrations similar to those of unrestrained mice. Treatment with 3-AB (0.5 and 5.0 mg/kg) during the restraint paradigm also facilitated habituation of the corticosterone response to restraint, and 3-AB (0.5 mg/kg) reduced the effect of repeated restraint on body mass. However, the immunoprotective effects of 3-AB and the endocrine and metabolic effects appear to be distinctly regulated because, unlike the endocrine and metabolic effects, the immunoprotective effects of 3-AB were independent of dose. These data suggest that PARP inhibitors may be useful to prevent compromised immune function in response to stressors.