Muizen

Imidacloprid (IMD), a neonicotinoid insecticide, is the most widely used insecticide on the planet. The purpose of this study was to examine the behavioural and biochemical effects of chronic in utero and early postnatal IMD exposure. Our treatment regimen entailed chronic exposure whereby pregnant mice were infused with 0.5 mg/kg/day of IMD via a subcutaneous osmotic mini-pump from gestational day 3 to postnatal day 21.

Schwarze Knopfaugen und dicke Bäckchen: Der Feldhamster sieht niedlich aus. Doch zu Gesicht bekommt den Nager im Norden kaum noch jemand, denn der Feldhamster (Cricetus cricetus) ist so gut wie ausgestorben. In Schleswig-Holstein und Mecklenburg-Vorpommern lebt nach Angaben der Deutschen Wildtier Stiftung kein einziger Feldhamster mehr. Und auch für Niedersachsen sieht es schlecht aus: Dort gibt es noch wenige Tiere rund um die die Hildesheimer Börde und Peine, aber auch hier schrumpft der Bestand. "Es ist fünf vor zwölf", sagt Biologe Peer Cyriacks von der Deutschen Wildtier Stiftung.

Neonicotinoids, a widely used group of pesticides designed to selectively bind to insect nicotinic acetylcholine receptors, were considered relatively safe for mammalian species. However, they have been found to activate vertebrate nicotinic acetylcholine receptors and could be toxic to the mammalian brain.

One year ago, an agency of the World Health Organization’s International Agency for Cancer Research (IARC) declared that glyphosate (or Roundup), the world’s most widely used herbicide, probably causes cancer. Then, in the fall, the European Food Safety Agency’s (EFSA) responded with an assessment that disagreed with the WHO’s findings. In response, 94 scientists came out in support of the IARC’s original findings. This week, the group—which includes scientists from around the world—released their article in the peer-reviewed Journal of Epidemiology and Community Health saying: The most appropriate and scientifically based evaluation of the cancers reported in humans and laboratory animals as well as supportive mechanistic data is that glyphosate is a probable human carcinogen. On the basis of this conclusion and in the absence of evidence to the contrary, it is reasonable to conclude that glyphosate formulations should also be considered likely human carcinogens. And their endorsement is no small matter. In fact, as the U.S. Environmental Protection Agency (EPA) reassesses the safety of glyphosate, and the U.S. Food and Drug Administration (FDA) plans to begin testing food for its residue, this volley has important implications.

The EPA document attached shows how Monsanto tried to convince the EPA to ‘disappear’ toxicology data, which confirmed that 18 out of 100 test-mice developed a rare form of kidney tumour when fed glyphosate. EPA scientists were concerned that when 18% of mice developed ‘rare’ kidney tumours when fed glyphosate; moreover, this was not a case of ‘false positives’ as Monsanto was claiming. The tumors in question were real and also rare. The EPA refused to allow Monsanto to argue that ‘false positives’ argument should be used to ‘dilute’ the findings. The EPA regulators in question fought back - to protect the Public Health; evidently the EPA still had a sense of ethics and public service at that time. Since glyphosate is the most widely used pesticide in the world today it is clear that Monsanto ‘persuaded’ the EPA to suppress its concerns and give Glyphosate an unconditional license. Glyphosate was found in Warburtons Bread and Jordans Muesli in the UK in 2014.

The objective of the present study was to evaluate immunotoxic effects of imidacloprid in female BALB/c mice. Imidacloprid was administered orally daily at 10, 5, or 2.5 mg/kg over 28 days. Specific parameters of humoral and cellular immune response including hemagglutinating antibody (HA) titer to sheep red blood cells (SRBC; T-dependent antigen), delayed type hypersensitivity (DTH) response to SRBC, and T-lymphocyte proliferation in response to phytohemagglutinin (PHA) were evaluated. The results showed that imidacloprid at high dose, specifically suppressed cell-mediated immune response as was evident from decreased DTH response and decreased stimulation index of T-lymphocytes to PHA. At this dose, there were also prominent histopathological alterations in spleen and liver. Histopathological analysis of footpad sections of mice revealed dose-related suppression of DTH response. Imidacloprid at low dose of 2.5 mg/kg/day did not produce any significant alterations in cellular and humoral immune response and it seemed to be an appropriate dose for assessment of ‘no observable adverse effects level’ for immunotoxicity in BALB/c mice. The results also indicated that imidacloprid has immunosuppressive effects at doses >5 mg/kg, which could potentially be attributed to direct cytotoxic effects of IMD against T cells (particularly TH cells) and that long-term exposure could be detrimental to the immune system.

Maternal smoking during pregnancy can impair performance of the exposed offspring in tasks that require auditory stimulus processing and perception; however, the tobacco component(s) responsible for these effects and the underlying neurobiological mechanisms remain uncertain. In this study, we show that administration of nicotine during mouse perinatal development can impair performance in an auditory discrimination paradigm when the exposed animals are mature. This suggests that nicotine disrupts auditory pathways via nicotinic acetylcholine receptors (nAChRs) that are expressed at an early stage of development. We have also determined that mice which lack nAChRs containing the β2 subunit (β2* nAChRs) exhibit similarly compromised performance in this task, suggesting that β2* nAChRs are necessary for normal auditory discrimination or that β2* nAChRs play a critical role in development of the circuitry required for task performance. In contrast, no effect of perinatal nicotine exposure or β2 subunit knockout was found on the acquisition and performance of a differential reinforcement of low rate task. This suggests that the auditory discrimination impairments are not a consequence of a general deficit in learning and memory, but may be the result of compromised auditory stimulus processing in the nicotine-exposed and knockout animals

This suggests that some constituent of smoke, such as the primary addictive component, nicotine, alters neurodevelopment. Although many effects of developmental nicotine exposure have been identified in humans and animal models, very few mechanistic studies have identified the molecular and anatomical basis for a defined behavioral consequence of developmental exposure. We show in this study that a mouse model of developmental nicotine exposure results in hypersensitive passive avoidance in adulthood. We have used transgenic mice in which β2 subunit containing nicotinic acetylcholine receptors (β2* nAChRs) are expressed exclusively on corticothalamic neurons (β2 tr(CT) mice) to identify the receptor subtypes involved and also to define the circuit level site of action responsible for this persistent, nicotine-induced behavioral phenotype. Further characterization of the native nAChRs expressed in this circuit indicates that both (α4)2(β2)3 and (α4)2(β2)2α5 nAChR subtypes are present in corticothalamic projections. Consistent with a role for (α4)2(β2)2α5 nAChRs in mediating the effect of developmental nicotine exposure on adult passive avoidance behavior, constitutive deletion of the α5 nAChR subunit also alters this behavior. A critical period for this developmental consequence of nicotine exposure was defined by limiting exposure to the early post-natal period. Taken together, these studies identify a novel consequence of developmental nicotine exposure in the mouse, define the nAChR subtypes and neural circuit involved in this behavioral change and delimit the neurodevelopmental period critical for vulnerability to a behavioral alteration that persists into adulthood.