Elevated levels of chloramines and chlorine detected near an indoor sports complex.

Chloramines (NH2Cl, NHCl2, and NCl3) are toxic compounds that can be created during the use of bleach-based disinfectants that contain hypochlorous acid (HOCl) and the hypochlorite ion (OCl-) as their active ingredients. Chloramines can then readily transfer from the aqueous-phase to the gas-phase. Atmospheric chemical ionization mass spectrometry using iodide adduct chemistry (I-CIMS) made observations across two periods (2014 and 2016) at an urban background site on the University of Leicester campus (Leicester, UK). Both monochloramine (NH2Cl) and molecular chlorine (Cl2) were detected and positively identified from calibrated mass spectra during both sampling periods and to our knowledge, this is the first detection of NH2Cl outdoors. Mixing ratios of NH2Cl reached up to 2.2 and 4.0 parts per billion by volume (ppbv), with median mixing ratios of 30 and 120 parts per trillion by volume (pptv) during the 2014 and 2016 sampling periods, respectively. Levels of Cl2 were observed to reach up to 220 and 320 pptv. Analysis of the NH2Cl and Cl2 data pointed to the same local source, a nearby indoor sports complex with a swimming pool and a cleaning product storage shed. No appreciable levels of NHCl2 and NCl3 were observed outdoors, suggesting the indoor pool was not likely to be the primary source of the observed ambient chloramines, as prior measurements made in indoor pool atmospheres indicate that NCl3 would be expected to dominate. Instead, these observations point to indoor cleaning and/or cleaning product emissions as the probable source of NH2Cl and Cl2 where the measured levels provide indirect evidence for substantial amounts transported from indoors to outdoors. Our upper estimate for total NH2Cl emissions from the University of Leicester indoor sports complexes scaled for similar sports complexes across the UK is 3.4 × 105 ± 1.1 × 105 µg h-1 and 0.0017 ± 0.00034 Gg yr-1, respectively. The Cl-equivalent emissions in HCl are only an order of magnitude less to those from hazardous waste incineration and iron and steel sinter production in the UK National Atmospheric Emissions Inventory (NAEI).

ERK pathway activation bidirectionally affects visual recognition memory and synaptic plasticity in the perirhinal cortex.

ERK 1,2 pathway mediates experience-dependent gene transcription in neurons and several studies have identified its pivotal role in experience-dependent synaptic plasticity and in forms of long term memory involving hippocampus, amygdala, or striatum. The perirhinal cortex (PRHC) plays an essential role in familiarity-based object recognition memory. It is still unknown whether ERK activation in PRHC is necessary for recognition memory consolidation. Most important, it is unknown whether by modulating the gain of the ERK pathway it is possible to bidirectionally affect visual recognition memory and PRHC synaptic plasticity. We have first pharmacologically blocked ERK activation in the PRHC of adult mice and found that this was sufficient to impair long term recognition memory in a familiarity-based task, the object recognition task (ORT). We have then tested performance in the ORT in Ras-GRF1 knock-out (KO) mice, which exhibit a reduced activation of ERK by neuronal activity, and in ERK1 KO mice, which have an increased activation of ERK2 and exhibit enhanced striatal plasticity and striatal mediated memory. We found that Ras-GRF1 KO mice have normal short term memory but display a long term memory deficit; memory reconsolidation is also impaired. On the contrary, ERK1 KO mice exhibit a better performance than WT mice at 72 h retention interval, suggesting a longer lasting recognition memory. In parallel with behavioral data, LTD was strongly reduced and LTP was significantly smaller in PRHC slices from Ras-GRF1 KO than in WT mice while enhanced LTP and LTD were found in PRHC slices from ERK1 KO mice.

Early environmental enrichment moderates the behavioral and synaptic phenotype of MeCP2 null mice.

BACKGROUND: Rett syndrome (RTT) is an X-linked progressive neurodevelopmental disorder characterized by a variety of symptoms including motor abnormalities, mental retardation, anxiety, and autism. Most of RTT cases are caused by mutations of MeCP2. In mice, impaired MeCP2 function results in synaptic deficits associated with motor, cognitive, and emotional alterations. Environmental enrichment (EE) is a rearing condition that enhances synapse formation and plasticity. Previous studies analyzing the effects of postweaning EE found limited effects on motor performance of male MeCP2 mutants. However, EE during early postnatal development produces powerful effects on neural development and plasticity. Thus, we tested whether early EE could ameliorate several phenotypes of male homozygous and female heterozygous MeCP2 mutants. METHODS: We investigated the effects of early EE on motor coordination, structural and functional synaptic plasticity, and brain-derived neurotrophic factor expression in male MeCP2 null mice. Anxiety-related behavior and spatial learning was analyzed in heterozygous MeCP2 female mice. RESULTS: In male mutants, EE modified excitatory and to a lesser extent inhibitory synaptic density in cerebellum and cortex, reversed the cortical long-term potentiation deficit and augmented cortical brain-derived neurotrophic factor levels. Environmental enrichment also ameliorated motor coordination and motor learning. In female heterozygous mice, a model closely mimicking some aspects of RTT symptoms, EE rescued memory deficits in the Morris water maze and decreased anxiety-related behavior. CONCLUSIONS: Early EE dramatically improves several phenotypes of MeCP2 mutants. Thus, environmental factors should be taken into account when analyzing phenotypes of MeCP2 knockout mice, an accepted model of RTT. Early EE might be beneficial in RTT patients.

Brain-derived neurotrophic factor (BDNF) overexpression in the forebrain results in learning and memory impairments.

In this study we analyzed the effect on behavior of a chronic exposure to brain-derived neurotrophic factor (BDNF), by analysing a mouse line overexpressing BDNF under the alphaCaMKII promoter, which drives the transgene expression exclusively to principal neurons of the forebrain. BDNF transgenic mice and their WT littermates were examined with a battery of behavioral tests, in order to evaluate motor coordination, learning, short and long-term memory formation. Our results demonstrate that chronic BDNF overexpression in the central nervous system (CNS) causes learning deficits and short-term memory impairments, both in spatial and instrumental learning tasks. This observation suggests that a widespread increase in BDNF in forebrain networks may result in adverse effects on learning and memory formation.

Brain-derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment.

Neurogenesis continues to occur in the adult mammalian hippocampus and is regulated by both genetic and environmental factors. It is known that exposure to an enriched environment enhances the number of newly generated neurons in the dentate gyrus. However, the mechanisms by which enriched housing produces these effects are poorly understood. To test a role for neurotrophins, we used heterozygous knockout mice for brain-derived neurotrophic factor (BDNF+/-) and mice lacking neurotrophin-4 (NT-4-/-) together with their wild-type littermates. Mice were either reared in standard laboratory conditions or placed in an enriched environment for 8 weeks. Animals received injections of the mitotic marker bromodeoxyuridine (BrdU) to label newborn cells. Enriched wild-type and enriched NT-4-/- mice showed a two-fold increase in hippocampal neurogenesis as assessed by stereological counting of BrdU-positive cells in the dentate gyrus and double labelling for BrdU and the neuronal marker NeuN. Remarkably, this enhancement of hippocampal neurogenesis was not seen in enriched BDNF+/- mice. Failure to up-regulate BDNF accompanied the lack of a neurogenic response in enriched BDNF heterozygous mice. We conclude that BDNF but not NT-4 is required for the environmental induction of neurogenesis.