Prenatal phencyclidine treatment induces behavioral deficits through impairment of GABAergic interneurons in the prefrontal cortex.

RATIONALE: We previously reported that prenatal treatment with phencyclidine (PCP) induces glutamatergic dysfunction in the prefrontal cortex (PFC), leading to schizophrenia-like behavioral deficits in adult mice. However, little is known about the prenatal effect of PCP treatment on other types of neurons. OBJECTIVES: We focused on γ-aminobutyric acid (GABA)-ergic interneurons and evaluated the effect of prenatal PCP exposure on the neurodevelopment of GABAergic interneurons in the PFC. METHODS: PCP was administered at the dose of 10 mg/kg/day to pregnant dams from embryonic day 6.5 to 18.5. After the pups were reared to adult, we analyzed their GABAergic system in the PFC using immunohistological, biochemical, and behavioral analyses in adulthood. RESULTS: The prenatal PCP treatment decreased the density of parvalbumin-positive cells and reduced the expression level of glutamic acid decarboxylase 67 (GAD67) and GABA content of the PFC in adults. Additionally, prenatal PCP treatment induced behavioral deficits in adult mice, such as hypersensitivity to PCP and prepulse inhibition (PPI) deficits. These behavioral deficits were ameliorated by pretreatment with the GABAB receptor agonist baclofen. Furthermore, the density of c-Fos-positive cells was decreased after the PPI test in the PFC of mice treated with PCP prenatally, and this effect was ameliorated by pretreatment with baclofen. CONCLUSIONS: These findings suggest that prenatal treatment with PCP induced GABAergic dysfunction in the PFC, which caused behavioral deficits.

Climate change, population immunity, and hyperendemicity in the transmission threshold of dengue.

BACKGROUND: It has been suggested that the probability of dengue epidemics could increase because of climate change. The probability of epidemics is most commonly evaluated by the basic reproductive number (R(0)), and in mosquito-borne diseases, mosquito density (the number of female mosquitoes per person [MPP]) is the critical determinant of the R(0) value. In dengue-endemic areas, 4 different serotypes of dengue virus coexist-a state known as hyperendemicity-and a certain proportion of the population is immune to one or more of these serotypes. Nevertheless, these factors are not included in the calculation of R(0). We aimed to investigate the effects of temperature change, population immunity, and hyperendemicity on the threshold MPP that triggers an epidemic. METHODS AND FINDINGS: We designed a mathematical model of dengue transmission dynamics. An epidemic was defined as a 10% increase in seroprevalence in a year, and the MPP that triggered an epidemic was defined as the threshold MPP. Simulations were conducted in Singapore based on the recorded temperatures from 1980 to 2009 The threshold MPP was estimated with the effect of (1) temperature only; (2) temperature and fluctuation of population immunity; and (3) temperature, fluctuation of immunity, and hyperendemicity. When only the effect of temperature was considered, the threshold MPP was estimated to be 0.53 in the 1980s and 0.46 in the 2000s, a decrease of 13.2%. When the fluctuation of population immunity and hyperendemicity were considered in the model, the threshold MPP decreased by 38.7%, from 0.93 to 0.57, from the 1980s to the 2000s. CONCLUSIONS: The threshold MPP was underestimated if population immunity was not considered and overestimated if hyperendemicity was not included in the simulations. In addition to temperature, these factors are particularly important when quantifying the threshold MPP for the purpose of setting goals for vector control in dengue-endemic areas.

Optimal timing of insecticide fogging to minimize dengue cases: modeling dengue transmission among various seasonalities and transmission intensities.

BACKGROUND: Dengue infection is endemic in many regions throughout the world. While insecticide fogging targeting the vector mosquito Aedes aegypti is a major control measure against dengue epidemics, the impact of this method remains controversial. A previous mathematical simulation study indicated that insecticide fogging minimized cases when conducted soon after peak disease prevalence, although the impact was minimal, possibly because seasonality and population immunity were not considered. Periodic outbreak patterns are also highly influenced by seasonal climatic conditions. Thus, these factors are important considerations when assessing the effect of vector control against dengue. We used mathematical simulations to identify the appropriate timing of insecticide fogging, considering seasonal change of vector populations, and to evaluate its impact on reducing dengue cases with various levels of transmission intensity. METHODOLOGY/PRINCIPAL FINDINGS: We created the Susceptible-Exposed-Infectious-Recovered (SEIR) model of dengue virus transmission. Mosquito lifespan was assumed to change seasonally and the optimal timing of insecticide fogging to minimize dengue incidence under various lengths of the wet season was investigated. We also assessed whether insecticide fogging was equally effective at higher and lower endemic levels by running simulations over a 500-year period with various transmission intensities to produce an endemic state. In contrast to the previous study, the optimal application of insecticide fogging was between the onset of the wet season and the prevalence peak. Although it has less impact in areas that have higher endemicity and longer wet seasons, insecticide fogging can prevent a considerable number of dengue cases if applied at the optimal time. CONCLUSIONS/SIGNIFICANCE: The optimal timing of insecticide fogging and its impact on reducing dengue cases were greatly influenced by seasonality and the level of transmission intensity. We suggest that these factors should be considered when planning a control strategy against dengue vectors.