Hyperphosphorylation of protein Tau in hippocampus may cause cognitive dysfunction of propofol-anesthetized rats.

OBJECTIVE: We aimed to explore the effect of hyperphosphorylation of Tau on cognitive function of propofol-anesthetized rats. MATERIALS AND METHODS: Thirty 2-month-old male Wistar rats weighing 180-220 g were randomly divided into 3 groups (n=10): group of treating with saline (C group), group of treating with propofol for 1 hour (P1) and 24 h (P24 group). The cognitive function of rats was tested by Morris water maze before and 1 h or 24 h after drug administration. The rats were then sacrificed. The protein and mRNA expression levels of GSK-3ß, total and phosphorylated Tau, cyclin D1, p27kip1 and c-caspase 3 in hippocampus were determined by Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. RESULTS: Compared with group C, the incubation period of P1 group and P24 group was prolonged, and the target quadrant retention time was shortened (p<0.05). There was no statistical difference between P1 and P24 group (p>0.05). Immunohistochemistry showed that compared with group C, p-Tau in hippocampus of P1 group and P24 group was highly expressed, with statistical difference (p<0.05). Western blot and RT-PCR showed that protein and mRNA expressions of GSK-3ß, phosphorylated Tau, cyclin D1 and c-caspase 3 in hippocampus of P1 and P24 groups were up-regulated (p<0.05). CONCLUSIONS: Propofol-induced cognitive dysfunction in rats may be related to the hyperphosphorylation of Tau that causes neuronal cells to re-enter the cell cycle, thus leading to apoptosis.

Impaired DNA damage response in cells expressing an exon 11-deleted murine Brca1 variant that localizes to nuclear foci.

Both human and mouse cells express an alternatively spliced variant of BRCA1, BRCA1-Delta11, which lacks exon 11 in its entirety, including putative nuclear localization signals. Consistent with this, BRCA1-Delta11 has been reported to reside in the cytoplasm, a localization that would ostensibly preclude it from playing a role in the nuclear processes in which its full-length counterpart has been implicated. Nevertheless, the finding that murine embryos bearing homozygous deletions of exon 11 survive longer than embryos that are homozygous for Brca1 null alleles suggests that exon 11-deleted isoforms may perform at least some of the functions of Brca1. We have analyzed both the full-length and the exon 11-deleted isoforms of the murine Brca1 protein. Our results demonstrate that full-length murine Brca1 is identical to human BRCA1 with respect to its cell cycle regulation, DNA damage-induced phosphorylation, nuclear localization, and association with Rad51. Surprisingly, we show that endogenous Brca1-Delta11 localizes to discrete nuclear foci indistinguishable from those found in wild-type cells, despite the fact that Brca1-Delta11 lacks previously defined nuclear localization signals. However, we further show that DNA damage-induced phosphorylation of Brca1-Delta11 is significantly reduced compared to full-length Brca1, and that gamma irradiation-induced Rad51 focus formation is impaired in cells in which only Brca1-Delta11 is expressed. Our results suggest that the increased viability of embryos bearing homozygous deletions of exon 11 may be due to expression of Brca1-Delta11 and suggest an explanation for the genomic instability that accompanies the loss of full-length Brca1.

Psychiatric co-morbidity among male heroin addicts: differences between hospital and incarcerated subjects in Taiwan.

AIMS: To examine the differences in psychiatric co-morbidity between hospital and incarcerated groups of heroin addicts in Taiwan. DESIGN: Life-time prevalence of DSM-III-R-based coexisting psychiatric disorders, including personality disorders, were surveyed. SETTINGS: A psychiatric hospital and two prisons. PARTICIPANTS: Two hundred and sixty heroin users who were incarcerated in prisons, and 47 heroin users who voluntarily sought help in a psychiatric hospital were interviewed by board-certified psychiatrists. MEASUREMENTS: Using two psychometric instruments, the Psychiatric Diagnostic Assessment (PDA) and the Structured Interview for DSM-III-R Personality Disorders (SIPD-R), psychiatric co-morbidity was assessed. FINDINGS: Different life-time rates of coexisting psychiatric disorders among heroin addicts in different settings were found: 83% of hospital subjects and 66% of incarcerated subjects were diagnosed as having at least one coexisting axis I or II disorder. The most prevalent coexisting DSM-III-R defined axis I disorders were additional substance use disorders (alcohol and methamphetamine), while the axis II disorder was antisocial personality disorder. The hospital group had a significantly higher prevalence rate of mood disorder (p < 0.001), paranoid personality disorder (p < 0.05) and antisocial personality disorder (p < 0.001) than the incarcerated group. CONCLUSIONS: We suggest that heroin addicts with coexisting psychiatric disorders receive relevant psychiatric treatment. Those with personality disorders, especially the antisocial type, should be considered for specialized therapeutic community programmes instead of incarceration.