The Chalcidoidea bush of life: evolutionary history of a massive radiation of minute wasps.

Chalcidoidea are mostly parasitoid wasps that include as many as 500 000 estimated species. Capturing phylogenetic signal from such a massive radiation can be daunting. Chalcidoidea is an excellent example of a hyperdiverse group that has remained recalcitrant to phylogenetic resolution. We combined 1007 exons obtained with Anchored Hybrid Enrichment with 1048 ultra-conserved elements (UCEs) for 433 taxa including all extant families, >95% of all subfamilies, and 356 genera chosen to represent the vast diversity of the superfamily. Going back and forth between the molecular results and our collective knowledge of morphology and biology, we detected bias in the analyses that was driven by the saturation of nucleotide data. Our final results are based on a concatenated analysis of the least saturated exons and UCE datasets (2054 loci, 284 106 sites). Our analyses support an expected sister relationship with Mymarommatoidea. Seven previously recognized families were not monophyletic, so support for a new classification is discussed. Natural history in some cases would appear to be more informative than morphology, as illustrated by the elucidation of a clade of plant gall associates and a clade of taxa with planidial first-instar larvae. The phylogeny suggests a transition from smaller soft-bodied wasps to larger and more heavily sclerotized wasps, with egg parasitism as potentially ancestral for the entire superfamily. Deep divergences in Chalcidoidea coincide with an increase in insect families in the fossil record, and an early shift to phytophagy corresponds with the beginning of the "Angiosperm Terrestrial Revolution". Our dating analyses suggest a middle Jurassic origin of 174 Ma (167.3-180.5 Ma) and a crown age of 162.2 Ma (153.9-169.8 Ma) for Chalcidoidea. During the Cretaceous, Chalcidoidea may have undergone a rapid radiation in southern Gondwana with subsequent dispersals to the Northern Hemisphere. This scenario is discussed with regard to knowledge about the host taxa of chalcid wasps, their fossil record and Earth's palaeogeographic history

NADPH oxidase elevations in pyramidal neurons drive psychosocial stress-induced neuropathology

Oxidative stress is thought to be involved in the development of behavioral and histopathological alterations in animal models of psychosis. Here we investigate the causal contribution of reactive oxygen species generation by the phagocyte NADPH oxidase NOX2 to neuropathological alterations in a rat model of chronic psychosocial stress. In rats exposed to social isolation, the earliest neuropathological alterations were signs of oxidative stress and appearance of NOX2. Alterations in behavior, increase in glutamate levels and loss of parvalbumin were detectable after 4 weeks of social isolation. The expression of the NOX2 subunit p47phox was markedly increased in pyramidal neurons of isolated rats, but below detection threshold in GABAergic neurons, astrocytes and microglia. Rats with a loss of function mutation in the NOX2 subunit p47phox were protected from behavioral and neuropathological alterations induced by social isolation. To test reversibility, we applied the antioxidant/NOX inhibitor apocynin after initiation of social isolation for a time period of 3 weeks. Apocynin reversed behavioral alterations fully when applied after 4 weeks of social isolation, but only partially after 7 weeks. Our results demonstrate that social isolation induces rapid elevations of the NOX2 complex in the brain. Expression of the enzyme complex was strongest in pyramidal neurons and a loss of function mutation prevented neuropathology induced by social isolation. Finally, at least at early stages, pharmacological targeting of NOX2 activity might reverse behavioral alterations

The Influence of Interleukin-1β on γ-Glutamyl Transpeptidase Activity in Rat Hippocampus

Summary Brain infections as well as peripheral challenges to the immune system lead to an increased production of interleukin1beta (IL-1β), a cytokine involved in leukocyte-mediated breakdown of the blood-brain barrier. The effects of IL-1β have been reported to depend on whether the route of administration is systemic or intracerebral. Using 50-day-old male rats, we compared the effects of IL-1β on brain γ-glutamyl transpeptidase (GGT; an enzymatic marker of brain capillary endothelium) at 2, 24 and 96 h after either an intravenous (i.v.) injection of 5 μg IL-1β or an intracerebroventricular (i.c.v. -lateral ventricle) infusion of 50 ng IL-1β. When the i.v. route was used, the GGT activity underwent small but significant changes; decreasing in the hippocampus 2 h after the i.v. injection, increasing 24 h later and returning to control levels at 96 h. No significant changes in the hippocampal GGT activity were observed at 2 and 24 h following the i.c.v. infusion. The GGT activity in the hypothalamus remained unchanged regardless of the route of IL-1β administrations. Similar changes in GGT activity were revealed histochemically. The labeling was found mainly in the capillary bed, the changes being most evident in the hippocampal stratum radiatum and stratum lacunosum-moleculare. A transient increase in GGT activity at 24 h, together with a less sharp delineation of GGT-stained vessels, may reflect IL-1β induced increased turnover of glutathione and/or oxidative stress, that may in turn, be related to altered permeability of the blood-brain barrier in some neurological and mental disorders, including schizophrenia

Chronic methamphetamine self-administration dysregulates 5-HT2A and mGlu2 receptor expression in the rat prefrontal and perirhinal cortex: Comparison to chronic phencyclidine and MK-801

Chronic methamphetamine (meth) abuse often turns into a compulsive drug-taking disorder accompanied by persistent cognitive deficits and re-occurring psychosis. Possible common neurobiological substrates underlying meth-induced deficits and schizophrenia remain poorly understood. Serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptors co-regulate psychosis-like behaviors and cognitive function in animals. Therefore, in the present study we examined the effects of chronic exposure to three different drugs known to produce persistent deficits in sensorimotor gating and cognition [meth, phencyclidine (PCP) and MK-801] on the expression of 5-HT2A and mGlu2 within the rat medial prefrontal cortex (PFC), dorsal hippocampus (dHPC) and perirhinal cortex (PRh). Adult male rats underwent 14 days of: (a) meth self-administration (6 h/day), (b) phencyclidine (PCP; 5 mg/kg, twice/day) administration, or (c) MK-801 (0.3 mg/kg, twice/day) administration. Seven days after the discontinuation of drug administration, tissues of interest were collected for protein expression analysis. We found that despite different pharmacological mechanism of action, chronic meth, PCP, and MK-801 similarly dysregulated 5-HT2A and mGlu2, as indicated by an increase in the 5-HT2A/mGlu2 expression ratio in the mPFC (all three tested drugs), PRh (meth and PCP), and dHPC (MK-801 only). Complementary changes in G-protein expression (increase in Gα and decrease in Gα) were also observed in the mPFC of meth animals. Finally, we found that 5-HT2A/mGlu2 cooperation can be mediated in part by the formation of the receptor heteromer in some, but not all cortical regions. In summary, these data suggest that a shift towards increased availability (and G-protein coupling) of cortical 5-HT2A vs. mGlu2 receptors may represent a common neurobiological mechanism underlying the emergence of psychosis and cognitive deficits observed in subjects with meth use disorder and schizophrenia

Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes

Cortical GABAergic dysfunction may underlie the pathophysiology of psychiatric disorders, including schizophrenia. Here, we characterized a mouse strain in which the essential NR1 subunit of the NMDA receptor (NMDAR) was selectively eliminated in 40–50% of cortical and hippocampal interneurons in early postnatal development. Consistent with the NMDAR hypofunction theory of schizophrenia, distinct schizophrenia-related symptoms emerged after adolescence, including novelty-induced hyperlocomotion, mating and nest-building deficits, as well as anhedonia-like and anxiety-like behaviors. Many of these behaviors were exacerbated by social isolation stress. Social memory, spatial working memory and prepulse inhibition were also impaired. Reduced expression of glutamic acid decarboxylase 67 and parvalbumin was accompanied by disinhibition of cortical excitatory neurons and reduced neuronal synchrony. Postadolescent deletion of NR1 did not result in such abnormalities. These findings suggest that early postnatal inhibition of NMDAR activity in corticolimbic GABAergic interneurons contributes to the pathophysiology of schizophrenia-related disorders.Fil: Belforte, Juan Emilio. Wayne State University; Estados Unidos. National Institute of Mental Health; Estados Unidos. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Zsiros, Veronika. National Institute of Mental Health; Estados UnidosFil: Sklar, Elyse R. National Institute of Mental Health; Estados Unidos. Wayne State University; Estados UnidosFil: Jiang, Zhihong. National Institute of Mental Health; Estados UnidosFil: Yu, Gu. University of Maryland; Estados UnidosFil: Li, Yuqing. University of Alabama at Birmingahm; Estados UnidosFil: Quinlan, Elizabeth M. University of Maryland; Estados UnidosFil: Nakazawa, Kazu. National Institute of Mental Health; Estados Unido