Tibolone modulates neuronal plasticity through regulating Tau,GSK3β/Akt/PI3K pathway and CDK5 p35/p25 complexes in the hippocampus of aged male mice

Aging is a key risk factor for cognitive decline and age-related neurodegenerative disorders. Also, an age-related decrease in sex steroid hormones may have a negative impact on the formation of neurofibrillary tangles(NFTs); these hormones can regulate Tau phosphorylation and the principal kinase GSK3β involved in this process. Hormone replacement therapy decreases NFTs, but it increases the risk of some types of cancer. However, other synthetic hormones such as tibolone(TIB) have been used for hormone replacement therapy. The aim of this work was to evaluate the long-term effects of TIB(0.01 mg/kg and 1 mg/kg, intragastrically for 12 weeks) on the content of total and hyperphosphorylated Tau(PHF-1) proteins and the regulation of GSK3β/Akt/PI3 K pathway and CDK5/p35/p25 complexes in the hippocampus of aged male mice. We observed that the content of PHF-1 decreased with TIB administration. In contrast, no changes were observed in the active form of GSK3β or PI3 K. TIB decreased the expression of the total and phosphorylated form of Akt while increased that of p110 and p85. The content of CDK5 was differentially modified with TIB: it was increased at low doses and decreased at high doses. When we analyzed the content of CDK5 activators, an increase was found on p35; however, the content of p25 decreased with administration of low dose of TIB. Our results suggest a possible mechanism of action of TIB in the hippocampus of aged male mice. Through the regulation of Tau and GSK3β/Akt/PI3 K pathway, and CDK5/p35/p25 complexes, TIB may modulate neuronal plasticity and regulate learning and memory processes.     

Disappearance of Female Genital Mutilation from the Bedouin Population of Southern Israel

IntroductionRecently, clinicians in Southern Israel perceived that the practice of female genital mutilation had disappeared entirely in the Bedouin population. We previously studied the prevalence of this practice in 1995.AimWe decided to survey again the Bedouin population focusing on those tribes previously reported to perform this practice.MethodsEighty percent of the interviews were done by an Arabic-speaking psychiatrist and 20% were done by an Arabic speaking nurse in the gynecologic clinic of a large Bedouin township or the gynecologic clinic of a smaller Bedouin township. Women were asked if they would be willing to answer a few questions about their past and if they were willing to have the gynecologist, with no additional procedure, note whether any operation had been performed on their genitalia.Main Outcome MeasuresPhysical examination by gynecologist and an oral questionnaire.ResultsOne hundred and thirty two women were examined. No cases of any scarring of the kind reported in the previous study were found on physical examination.ConclusionsFGM has apparently disappeared over 15 years in a population in which it was once prevalent. Halila S, Belmaker RH, Rabia YA, Froimovici M, and Applebaum J. Disappearance of female genital mutilation from the bedouin population of Southern Israel. J Sex Med 2009;6:70–73.     

The familial association of tourette's disorder and ADHD: The impact of OCD symptoms

Tourette's disorder (TD) frequently co‐occurs with attention‐deficit/hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). While the relationship between TD and OCD suggests that they share etiological factors, the exact relationship between TD and ADHD is less clear. The goal of the current analyses was to understand better the familial relationship between DSM‐IV ADHD and TD. Direct interview diagnostic data from a case–control study of 692 relatives of 75 comorbid TD and ADHD (TD + ADHD), 74 TD without ADHD (TD Only), 41 ADHD without TD (ADHD Only), and 49 control probands were analyzed. Hierarchical loglinear modeling was used to explore association patterns between TD, ADHD, and OCD or sub‐clinical OCD (OCD/OCDsub) diagnoses among the 190 affected probands and their 538 relatives. The presence of OCD or OCDsub diagnosis in a proband was associated with a significantly increased risk of comorbid TD + ADHD in his/her relatives. The finding of an association between TD, ADHD and a proband OCD/OCDsub diagnosis was unexpected. The current results suggest that TD, ADHD, and OCD symptoms have overlapping neurobiology when occurring in families of TD and/or ADHD probands. © 2011 Wiley‐Liss, Inc.     

Chromosomal aberrations in railroad transit workers: Effect of genetic polymorphisms

Complex chemical mixtures are transported by train from Russia to Finland for further shipment. Here, we studied if exposure to genotoxic components among these substances could affect chromosomal aberrations (CAs) in peripheral lymphocytes of workers handling the tank cars. An initial survey among 48 railroad workers and 39 referents (male smokers and nonsmokers) showed an elevation of CAs. A campaign was started to reduce exposures through preventive measures. Five years later, 51 tank car workers and 40 age‐matched referents (all nonsmoking men) were studied for CAs and genetic polymorphisms of xenobiotic metabolism (EPHX1, GSTM1, GSTP1, GSTT1, NAT1, NAT2), DNA repair (ERCC2, ERCC5, XPA, XPC, XRCC1, XRCC3), and folate metabolism (MTHFR, MTR). No increase in CAs was seen in the exposed group, suggesting that the preventive measures had been successful. However, a positive association existed between exposure duration and CA level among the exposed subjects. The level of chromosome‐type breaks was actually lower in the exposed workers than the referents, particularly among MTHFR wild‐type homozygotes or XRCC3 codon 241 variant allele carriers, suggesting modulation of CA frequency by folate metabolism and DNA repair. An interaction was observed between the occupational exposure and MTHFR, EPHX1, and MTR genotypes in determining CA level. The NAT2, ERCC2 exon 10, and XRCC1 codon 194 polymorphisms also affected CA frequency. Our findings suggest that handling of tank cars containing complex chemical mixtures poses a genotoxic risk, which may be reduced by preventive measures. Several genetic polymorphisms seem to modify the genotoxic effect or baseline CA level. Environ. Mal. Mutagen. 2009. © 2009 Wiley‐Liss, Inc.