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Brain matrix metalloproteinases (MMPs) have been recently implicated in alcohol addiction; however, the molecular mechanisms remain poorly understood. Matrix metalloproteinase-9 (MMP-9), an extrasynaptic protease, is the best described MMP that is thought to regulate addictive behavior. In the present study, the effect of MMP-9 overexpression on hippocampal neuron plasticity and alcoholic behavior was assessed in spontaneous alcohol drinking mice. Two-bottle choice model showed that the overexpression of MMP-9 in the hippocampus developed by adeno-associated virus (AAV) could decrease alcohol consumption and preference, but did not affect taste preference, which was tested using saccharin or quinine solutions. Dendritic spines number of hippocampal neurons was observed by Golgi staining. Compared with the alcohol treatment group, the density of dendritic spines in the hippocampus of alcohol drinking mice was decreased in alcohol + MMP-9 group. Western blot analysis indicated that GluN1 expression in the hippocampus of alcohol drinking group was lower than that in the control group, while the expression of GluN1 was increased in MMP-9 overexpressing mice. MMP-9 also regulated the depolymerization of actin filaments, which induced behavioral changes in mice. Taken together, overexpression of MMP-9 in the hippocampal neurons of mice resulted in decreased dendritic spine density and F-actin/G-actin ratio, which might be the crucial reason for the significant decrease in alcohol consumption in alcohol drinking mice. MMP-9 might be considered as a novel target studying the molecular mechanism of alcohol drinking.

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Objective To determine the status of false-positive report of congenital syphilis (CS),to analyze the possible causes of mis-diagnosis.Methods Basic information on CS in Shanghai in the past five years was collected.We identified infants diagnosed with CS and followed up the sero- logical reactivity of those patients and their mothers.The serological reactivity[rapid plasmin reagin (RPR)and treponema palidum hemagglutination assay(TPPA)]of infants was followed-up for up to 24 months,or until both antibodies turned to negative.The medical history of the mothers was col- lected,and their sera were examined for syphilitic antibodies.Results Total 99 infants diagnosed with CS were recruited. The major diagnostic method was treponemal antibody detection.Only 31.3% of the 99 infants exhibited clinical symptoms or syphilis-like symptoms at delivery.The cumu- lative RPR loss rates of the infants were 44.2%,64.0%,72.7%,83.9% and 87.1% at 1-3,3-6,6- 12,12-18 and 18-24 months after birth,respectively.The cumulative TPPA loss rates were 1.1%, 18.6%,44.6%,66.7% and 74.4% for 1-3,3-6,6-12,12-18 and 18-24 months after birth,respec- tively.TPPA remained positive in all mothers with syphilis.Conclusion The diagnosis of congenital syphilis determined solely by the positive tests of RPR and TPPA is unreliable and can be misdiagno- sis.The diagnosis and management of congenital syphilis should be urgently improved,and that the profes- sional health institutions should perform and closely monitor the quality controls in the diagnosis of CS and standardize the intervention strategy of maternal syphilis.