Background The prevalence of post-operative cognitive disturbance, coupled with growing in vitro, cell and animal evidence suggesting anesthetic effects on neurodegeneration, calls for further study of the interaction between surgical care and Alzheimer neuropathology. Here, we study human cerebral spinal fluid (CSF) biomarkers perioperatively. Methods Eleven patients undergoing idiopathic nasal CSF leak correction joined this Institutional Review Board approved study. Lumbar subarachnoid catheters were placed prior to the procedure. Anesthesia was total intravenous anesthesia (propofol/remifentanil) or inhalational (sevoflurane), depending on provider choice. CSF samples were taken after catheter placement (base), at procedure end (0h), and then at 6, 24 and 48h. CSF was analyzed using xMAP Luminex immunoassay (Luminex, Austin, TX). Results Patients: 53±6 yrs old; 8 women; 4 received intravenous anesthesia, 6 sevoflurane, 1 mixed. Procedures lasted 6.4 ± 2h. Mean CSF amyloid-β1-42 remained unchanged, but total-tau and phosphorylated-tau181P increased progressively until at least 48h. Total-tau, phosphorylated-tau or amyloid-β1-42 levels were not different between anesthetic groups. CSF interleukin-10, S100B and tumor necrosis factor alpha were increased similarly in both anesthetic groups at 24h, but interleukin-6 was increased more in the inhalational group. Conclusion These data indicate a robust neuroinflammatory response, including not only the usual markers (interleukin-6, tumor necrosis factor α, interleukin-10), but also S100B and tau, markers of injury. The total-tau/amyloid-β1-42 ratio increased in a pattern consistent with Alzheimer disease, largely due to an increase in total-tau rather than a decline in amyloid-β1-42. The differences in CSF interleukin-6 levels, suggest that anesthetic management may make a difference in neuroinflammatory response.

DTNBP1 (dystrobrevin binding protein 1) remains a top candidate gene in schizophrenia. Reduced expression of this gene and of its encoded protein, dysbindin-1, have been reported in the brains of schizophrenia cases. It has not been established, however, if the protein reductions encompass all dysbindin-1 isoforms or if they are associated with decreased DTNBP1 gene expression. Using a matched pairs design in which each of 28 Caucasian schizophrenia cases was matched in age and sex to a normal Caucasian control, Western blotting of whole-tissue lysates of dorsolateral prefrontal cortex (DLPFC) revealed significant reductions in dysbindin-1C (but not in dysbindin-1A or -1B) in schizophrenia (P = 0.022). These reductions occurred without any significant change in levels of the encoding transcript in the same tissue samples and in the absence of the only DTNBP1 risk haplotype for schizophrenia reported in the USA. Indeed, no significant correlations were found between case-control differences in any dysbindin-1 isoform and the case-control differences in its encoding mRNA. Consequently, the mean 60% decrease in dysbindin-1C observed in 71% of our case-control pairs appears to reflect abnormalities in mRNA translation and/or processes promoting dysbindin-1C degradation (e.g. oxidative stress, phosphorylation and/or ubiquitination). Given the predominantly post-synaptic localization of dysbindin-1C and known post-synaptic effects of dysbindin-1 reductions in the rodent equivalent of the DLPFC, the present findings suggest that decreased dysbindin-1C in the DLPFC may contribute to the cognitive deficits of schizophrenia by promoting NMDA receptor hypofunction in fast-spiking interneurons.

Chicken growth traits are important economic traits in broilers. A large number of studies are available on finding genetic factors affecting chicken growth. However, most of these studies identified chromosome regions containing putative quantitative trait loci and finding causal mutations is still a challenge. In this genome-wide association study (GWAS), we identified a narrow 1.5 Mb region (173.5–175 Mb) of chicken (Gallus gallus) chromosome (GGA) 1 to be strongly associated with chicken growth using 47,678 SNPs and 489 F2 chickens. The growth traits included aggregate body weight (BW) at 0–90 d of age measured weekly, biweekly average daily gains (ADG) derived from weekly body weight, and breast muscle weight (BMW), leg muscle weight (LMW) and wing weight (WW) at 90 d of age. Five SNPs in the 1.5 Mb KPNA3-FOXO1A region at GGA1 had the highest significant effects for all growth traits in this study, including a SNP at 8.9 Kb upstream of FOXO1A for BW at 22–48 d and 70 d, a SNP at 1.9 Kb downstream of FOXO1A for WW, a SNP at 20.9 Kb downstream of ENSGALG00000022732 for ADG at 29–42 d, a SNP in INTS6 for BW at 90 d, and a SNP in KPNA3 for BMW and LMW. The 1.5 Mb KPNA3-FOXO1A region contained two microRNA genes that could bind to messenger ribonucleic acid (mRNA) of IGF1, FOXO1A and KPNA3. It was further indicated that the 1.5 Mb GGA1 region had the strongest effects on chicken growth during 22–42 d.

Sandy mice have a deletion mutation in the gene encoding dysbindin-1, Dtnbp1, with consequent reduction of the protein in heterozygotes and its loss in homozygotes. The sandy mouse thus serves as an animal model of dysbindin-1 function. Since this protein is concentrated in synaptic tissue and affects transmitter release, it may affect neuronal processes that mediate behavior. To investigate the neurobehavioral effects of the Dtnbp1 mutation, we studied littermate sandy and wild-type controls on a C57BL/6J genetic background. The three animal groups were indistinguishable in their external physical characteristics, sensorimotor skills, and indices of anxiety-like behaviors. In the open field, however, homozygous animals were hyperactive and appeared to show less habituation to the initially novel environment. In the Morris water maze, homozygous animals displayed clear deficits in spatial learning and memory with marginal deficits in visual association learning. Apart from the last mention deficits, these abnormalities are consistent with hippocampal dysfunction and in some cases with elevated dopaminergic transmission via D2 dopamine receptors. Since similar deficits in spatial learning and memory have been found in schizophrenia, where decreased dysbindin-1 has been found in the hippocampus, the sandy mouse may also model certain aspects of cognition and behavior relevant to schizophrenia.

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