Sirtuins function with other biogenic molecules to promote adaptation to caloric restriction in a broad spectrum of eukaryotic species. Sirtuin pathways also converge in the mammalian brain where they appear to protect neurons from nutrient stress. However, few anatomical studies on sirtuins (e.g., SIRT1) are available, particularly those detailing the spatial distribution and subcellular localization pattern of SIRT1 in the brain parenchyma. Here, we report the characterization of a panel of SIRT1-specific antibodies within rodent (i.e., rat and mouse) and human central nervous systems. Immunocytochemical and Western blot analyses indicate that the subcellular localization of SIRT1 is predominantly nuclear throughout the rodent brain and spinal cord. A similar subcellular distribution pattern of SIRT1 was detected in human central nervous system material. SIRT1 is ubiquitously present in areas of the brain especially susceptible to age-related neurodegenerative states (e.g., the prefrontal cortex, hippocampus and basal ganglia). Further, we show no apparent species-specific differences in the subcellular localization pattern of rodent versus human SIRT1. Finally, we identify the chemical phenotype of SIRT1-containing neurons in a number of brain sites that are strongly compromised by aging. These data provide additional and important anatomical findings for the role of SIRT1 in the mammalian brain and suggest that SIRT1 pathways are broadly distributed in neurons most susceptible to senescence injury. Activating endogenous sirtuin pathways may, therefore, offer a therapeutic approach to delay and/or treat human agerelated diseases. Anat Rec, 293:1024Rec, 293: -1032Rec, 293: , 2010. V V C 2010 Wiley-Liss, Inc.Key words: basal ganglia; hippocampus; parvalbumin; prefrontal cortex; tyrosine hydroxylaseSirtuins are histone nicotinamide adenosine dinucleotide (NAD)-dependent deacetylases widely recognized for their link to eukaryotic life span (Guarente and Picard, 2005;Michan and Sinclair, 2007). Silent information regulator 1 (SIRT1), the most studied among the seven mammalian sirtuins, increases when situations favor longevity, such as caloric restriction or following treatment with the polyphenol resveratrol. SIRT1 resides primarily in the cell nucleus where it targets several nonhistone transcriptional regulators including p53, heat shock factor 1 (HSF1), forkhead transcription factor (FOXO), NF-jB, and peroxisome proliferator-activator receptor-c coactivator-1a (PGC-1a). These factors promote adaptation to caloric restriction by regulating agerelated programs of replicative senescence, protein homeostasis, inflammatory function, and energy metabolism (Vaziri et al., 2001;Motta et al., 2004;Yeung et al.,

Ketamine exerts powerful anesthetic, psychotic and anti-depressant effects in both healthy volunteers and clinically-depressed patients. Although ketamine targets particular glutamate receptors, there is a dearth of evidence for additional, alternative molecular substrates for the behavioral actions of this NMDA receptor antagonist drug. Here, we provide behavioral and molecular evidence for the actions of ketamine using a new vertebrate model for psychiatric disorders: the zebrafish. Sub-anesthetic doses of ketamine produced a variety of abnormal behaviors in zebrafish that were qualitatively analogous to those previously measured in humans and rodents treated with drugs that produce transient psychosis. In addition, we revealed that the transcription factor Phox2b is a molecular substrate for the actions of ketamine, particularly during periods of hypoxic stress. Finally, we also show that SIRT1, a histone deacetylase widely recognized for its link to cell survival is also affected by hypoxia crises. These results establish a relevant assay system in which the effects of psychotomimetic drugs can rapidly be assessed, and provide a plausible and novel neuronal mechanism through which ketamine affects critical sensory circuits that monitor breathing behavior.

This review discusses the biology and behavior of Propionibacterium acnes (P. acnes), a dominant bacterium species of the skin biogeography thought to be associated with transmission, recurrence and severity of disease. More specifically, we discuss the ability of P. acnes to invade and persist in epithelial cells and circulating macrophages to subsequently induce bouts of sarcoidosis, low-grade inflammation and metastatic cell growth in the prostate gland. Finally, we discuss the possibility of P. acnes infiltrating the brain parenchyma to indirectly contribute to pathogenic processes in neurodegenerative disorders such as those observed in Parkinson's disease (PD).