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1.
Neuropsychopharmacology ; 41(5): 1404-15, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26383016

RESUMO

Elucidating how the brain's serotonergic network mediates diverse behavioral actions over both relatively short (minutes-hours) and long period of time (days-weeks) remains a major challenge for neuroscience. Our relative ignorance is largely due to the lack of technologies with robustness, reversibility, and spatio-temporal control. Recently, we have demonstrated that our chemogenetic approach (eg, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) provides a reliable and robust tool for controlling genetically defined neural populations. Here we show how short- and long-term activation of dorsal raphe nucleus (DRN) serotonergic neurons induces robust behavioral responses. We found that both short- and long-term activation of DRN serotonergic neurons induce antidepressant-like behavioral responses. However, only short-term activation induces anxiogenic-like behaviors. In parallel, these behavioral phenotypes were associated with a metabolic map of whole brain network activity via a recently developed non-invasive imaging technology DREAMM (DREADD Associated Metabolic Mapping). Our findings reveal a previously unappreciated brain network elicited by selective activation of DRN serotonin neurons and illuminate potential therapeutic and adverse effects of drugs targeting DRN neurons.


Assuntos
Ansiedade/fisiopatologia , Depressão/fisiopatologia , Núcleo Dorsal da Rafe/fisiologia , Neurônios Serotoninérgicos/fisiologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiologia , Ritmo Circadiano , Drogas Desenhadas/administração & dosagem , Núcleo Dorsal da Rafe/efeitos dos fármacos , Núcleo Dorsal da Rafe/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Neurônios Serotoninérgicos/efeitos dos fármacos , Neurônios Serotoninérgicos/metabolismo , Fatores de Tempo
2.
Arch Environ Contam Toxicol ; 64(1): 130-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23080409

RESUMO

The Yankee Fork is a large tributary of the Salmon River located in central Idaho, USA, with an extensive history of placer and dredge-mining activities. Concentrations of selenium (Se) and mercury (Hg) in various aquatic trophic levels were measured in the Yankee Fork during 2001 and 2002. Various measurements of fish health were also performed. Sites included four on the mainstem of the Yankee Fork and two off-channel sites in partially reclaimed dredge pools used as rearing habitat for cultured salmonid eggs and fry. Hg concentrations in whole mountain whitefish and shorthead sculpin ranged from 0.28 to 0.56 µg/g dry weight (dw), concentrations that are generally less than those reported to have significant impacts on fish. Biofilm and invertebrates ranged from 0.05 to 0.43 µg Hg/g dw. Se concentrations measured in biota samples from the Yankee Fork were greater than many representative samples collected in the Snake and Columbia watersheds and often exceeded literature-based toxic thresholds. Biofilm and invertebrates ranged from 0.58 to 4.66 µg Se/g dw. Whole fish ranged from 3.92 to 7.10 µg Se/g dw, and gonads ranged from 6.91 to 31.84 µg Se/g dw. Whole-body Se concentrations exceeded reported toxicological thresholds at three of four sites and concentrations in liver samples were mostly greater than concentrations shown to have negative impacts on fish health. Histological examinations performed during this study noted liver abnormalities, especially in shorthead sculpin, a bottom-dwelling species.


Assuntos
Monitoramento Ambiental , Peixes/metabolismo , Mercúrio/metabolismo , Selênio/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Peixes/fisiologia , Idaho , Mercúrio/análise , Mercúrio/toxicidade , Selênio/análise , Selênio/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
3.
Environ Monit Assess ; 115(1-3): 381-93, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16648955

RESUMO

Portions of the Boulder River watershed contain elevated concentrations of arsenic, cadmium, copper, lead, and zinc in water, sediment, and biota. We measured concentrations of As, Cd, Cu, Pb, and Zn in biofilm and macroinvertebrates, and assessed macroinvertebrate assemblage and aquatic habitat with the objective of monitoring planned remediation efforts. Concentrations of metals were generally higher in downstream sites compared with upstream or reference sites, and two sites contained metal concentrations in macroinvertebrates greater than values reported to reduce health and survival of resident trout. Macroinvertebrate assemblage was correlated with metal concentrations in biofilm and macroinvertebrates. However, macroinvertebrate metrics were significantly correlated with a greater number of biofilm metals (8) than metals in invertebrates (4). Lead concentrations in biofilm appeared to have the most significant impact on macroinvertebrate assemblage. Metal concentrations in macroinvertebrates were directly proportional to concentrations in biofilm, indicating biofilm as a potential surrogate for monitoring metal impacts in aquatic systems.


Assuntos
Monitoramento Ambiental/métodos , Sedimentos Geológicos/microbiologia , Invertebrados , Metais Pesados/análise , Rios , Poluentes Químicos da Água/análise , Animais , Biofilmes/crescimento & desenvolvimento , Invertebrados/química , Invertebrados/crescimento & desenvolvimento , Montana
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