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1.
Mol Psychiatry ; 22(3): 466-475, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27240530

RESUMO

Anxiety disorders constitute a major disease and social burden worldwide; however, many questions concerning the underlying molecular mechanisms still remain open. Besides the involvement of the major excitatory (glutamate) and inhibitory (gamma aminobutyric acid (GABA)) neurotransmitter circuits in anxiety disorders, the stress system has been directly implicated in the pathophysiology of these complex mental illnesses. The glucocorticoid receptor (GR) is the major receptor for the stress hormone cortisol (corticosterone in rodents) and is widely expressed in excitatory and inhibitory neurons, as well as in glial cells. However, currently it is unknown which of these cell populations mediate GR actions that eventually regulate fear- and anxiety-related behaviors. In order to address this question, we generated mice lacking the receptor specifically in forebrain glutamatergic or GABAergic neurons by breeding GRflox/flox mice to Nex-Cre or Dlx5/6-Cre mice, respectively. GR deletion specifically in glutamatergic, but not in GABAergic, neurons induced hypothalamic-pituitary-adrenal axis hyperactivity and reduced fear- and anxiety-related behavior. This was paralleled by reduced GR-dependent electrophysiological responses in the basolateral amygdala (BLA). Importantly, viral-mediated GR deletion additionally showed that fear expression, but not anxiety, is regulated by GRs in glutamatergic neurons of the BLA. This suggests that pathological anxiety likely results from altered GR signaling in glutamatergic circuits of several forebrain regions, while modulation of fear-related behavior can largely be ascribed to GR signaling in glutamatergic neurons of the BLA. Collectively, our results reveal a major contribution of GRs in the brain's key excitatory, but not inhibitory, neurotransmitter system in the regulation of fear and anxiety behaviors, which is crucial to our understanding of the molecular mechanisms underlying anxiety disorders.


Assuntos
Transtornos de Ansiedade/fisiopatologia , Receptores de Glucocorticoides/metabolismo , Receptores de Glutamato/metabolismo , Tonsila do Cerebelo/metabolismo , Animais , Ansiedade/fisiopatologia , Complexo Nuclear Basolateral da Amígdala/metabolismo , Corticosterona/metabolismo , Fármacos Atuantes sobre Aminoácidos Excitatórios/metabolismo , Medo/fisiologia , GABAérgicos/metabolismo , Neurônios GABAérgicos/metabolismo , Ácido Glutâmico/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Camundongos , Camundongos Knockout , Neurônios/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Prosencéfalo/metabolismo , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/metabolismo
2.
Andrologia ; 14(2): 113-7, 1982.
Artigo em Alemão | MEDLINE | ID: mdl-7103130

RESUMO

The new electronic spermcounter was developed to make andrological routine work easier. The apparatus is a complete microcomputer and has three main functions: The counter function allows to determine the number of spermatozoa and round cells at the same time. The morphological function allows the detailed morphological analysis of stained spermatozoa specimen within a reasonable time. Besides the determination of normal and pathlogical forms a more exact differentiation of the respective pathological spermatozoon is possible. The timer function guarantees the exact timing of the evaluation of sperm motility. We judge the motility immediately after ejaculation and 30, 60, 120, 240 minutes later. Using the electronic sperm counter in the andrological routine laboratory and for detailed morphological studies we observed an improvement of the quality of our results and a remarkable saving of time. It is evident, that the spermcounter is a valuable equipment for all institutions performing investigations on sperm, of instance clinical and practical andrologists, veterinarians and scientists working in the field of reproduction.


Assuntos
Sêmen/citologia , Contagem de Espermatozoides/instrumentação , Motilidade dos Espermatozoides , Espermatozoides/citologia , Humanos , Cinética , Masculino , Microcomputadores
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