Deletion of JMJD2B in neurons leads to defective spine maturation, hyperactive behavior and memory deficits in mouse.

JMJD2B is a histone demethylase enzyme that regulates gene expression through demethylation of H3K9me3. Although mutations of JMJD2B have been suggested to be responsible for neurodevelopmental disorders, the function of JMJD2B in the central nervous system (CNS) remains to be elucidated. Here we show that JMJD2B has a critical role in the development of the CNS. We observed JMJD2B expression, which was especially strong in the hippocampus, throughout the CNS from embryonic periods through adulthood. We generated neuron-specific JMJD2B-deficient mice using the cre-loxP system. We found an increase in total spine number, but a decrease in mature spines, in the CA1 region of the hippocampus. JMJD2B-deficient mice exhibited hyperactive behavior, sustained hyperactivity in a novel environment, deficits in working memory and spontaneous epileptic-like seizures. Together these observations indicate that JMJD2B mutant mice display symptoms reminiscent of neurodevelopmental disorders. Our findings provide evidence for the involvement of histone demethylation in the formation of functional neural networks during development.

Atomoxetine reverses locomotor hyperactivity, impaired novel object recognition, and prepulse inhibition impairment in mice lacking pituitary adenylate cyclase-activating polypeptide.

Attention-deficit/hyperactivity disorder (ADHD) is a complex neurobehavioral disorder that is characterized by attention difficulties, impulsivity, and hyperactivity. A non-stimulant drug, atomoxetine (ATX), which is a selective noradrenaline reuptake inhibitor, is widely used for ADHD because it exhibits fewer adverse effects compared to conventional psychostimulants. However, little is known about the therapeutic mechanisms of ATX. ATX treatment significantly alleviated hyperactivity of pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient (PACAP(-/-)) mice with C57BL/6J and 129S6/SvEvTac hybrid background. ATX also improved impaired novel object recognition memory and prepulse inhibition in PACAP(-/-) mice with CD1 background. The ATX-induced increases in extracellular noradrenaline and dopamine levels were significantly higher in the prefrontal cortex of PACAP(-/-) mice compared to wild-type mice with C57BL/6J and 129S6/SvEvTac hybrid background. These results suggest that ATX treatment-induced increases in central monoamine metabolism may be involved in the rescue of ADHD-related abnormalities in PACAP(-/-) mice. Our current study suggests that PACAP(-/-) mice are an ideal rodent model with predictive validity for the study of ADHD etiology and drug development. Additionally, the potential effects of differences in genetic background of PACAP(-/-) mice on behaviors are discussed.

Development and utilization of a drug information system in the Japanese pharmaceutical industry.

Pharmaceutical companies are responsible for providing updated, relevant information on the efficacy, safety and quality of drugs to medical professionals and finally to patients. To fulfill this responsibility, we must always endeavour to collect and evaluate the relevant information. We developed a drug information database system called Advanced Medical Online Network of Daiichi (AMOND) to manage various information generated during development of new products and after launch of the products using the classification format for retrieval. This system has been used for 9 years for the purpose of supporting medical representatives who play a primary role in the drug information services in the pharmaceutical industry. This system is incorporated into an on-line network system, and can be directly accessed by more than 1200 people at 11 branch offices and more than 110 subbranches all over the country. We upgraded this system to AMOND-II to improve the function, including retrieval and output abilities. As a result, utilization by users of this system increased six times. We report on the improved system, AMOND-II and our experience of the system.

[The obstetric prognosis and neonatal outcome of pregnant women with psychiatric disorders].

Obstetric prognosis and neonatal outcome of pregnant women with psychiatric disorders were retrospectively investigated. 1. Out of 1.472 deliveries at Saga Medical School from April 1983 to July 1988, there were fourteen cases (0.95%) involving psychiatric disorders-six of epilepsy, one of anxiety neurosis and seven of schizophrenias. 2. Total blood loss was relatively great in four epileptic patients. However, the general prognosis for each was good and the neonatal outcome was uneventful. 3. As for schizophrenic patients, six out of seven cases grew worse during the pregnancy and four in the postpartum period. Three cases underwent cesarean section due to their mental illness. 4. We made inquiries about the postpartum life of schizophrenic mothers and children, and received five answers (70.1%). It was found that schizophrenic mothers could not bring up the baby by themselves; they needed the help of their husbands and their own mothers. It is concluded that consistent management by both psychiatrist and obstetrician from the antepartum period to postpartum life are required for psychotic mothers and their children to obtain a favorable prognosis, and a follow-up system is desirable for the physical as well as the mental growth of the infants.