RESUMO
BACKGROUND: Long-term synaptic plasticity is a basic ability of the brain to dynamically adapt to external stimuli and regulate synaptic strength and ultimately network function. It is dysregulated by behavioral stress in animal models of depression and in humans with major depressive disorder. Antidepressants have been shown to restore disrupted synaptic plasticity in both animal models and humans; however, the underlying mechanism is unclear. METHODS: We examined modulation of synaptic plasticity by selective serotonin reuptake inhibitors (SSRIs) in hippocampal brain slices from wild-type rats and serotonin transporter (SERT) knockout mice. Recombinant voltage-gated calcium (Ca2+) channels in heterologous expression systems were used to determine the modulation of Ca2+ channels by SSRIs. We tested the behavioral effects of SSRIs in the chronic behavioral despair model of depression both in the presence and in the absence of SERT. RESULTS: SSRIs selectively inhibited hippocampal long-term depression. The inhibition of long-term depression by SSRIs was mediated by a direct block of voltage-activated L-type Ca2+ channels and was independent of SERT. Furthermore, SSRIs protected both wild-type and SERT knockout mice from behavioral despair induced by chronic stress. Finally, long-term depression was facilitated in animals subjected to the behavioral despair model, which was prevented by SSRI treatment. CONCLUSIONS: These results showed that antidepressants protected synaptic plasticity and neuronal circuitry from the effects of stress via a modulation of Ca2+ channels and synaptic plasticity independent of SERT. Thus, L-type Ca2+ channels might constitute an important signaling hub for stress response and for pathophysiology and treatment of depression.
Assuntos
Antidepressivos/uso terapêutico , Canais de Cálcio Tipo L/metabolismo , Proteínas de Ligação a RNA/metabolismo , Estresse Psicológico/tratamento farmacológico , Transmissão Sináptica/efeitos dos fármacos , Fatores Etários , Animais , Células CHO , Cloreto de Cádmio/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/genética , Cricetulus , Modelos Animais de Doenças , Estimulação Elétrica , Feminino , Fluvoxamina/uso terapêutico , Células HEK293 , Elevação dos Membros Posteriores/psicologia , Hipocampo/citologia , Humanos , Técnicas In Vitro , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/genética , Nifedipino/farmacologia , Paroxetina/farmacologia , Técnicas de Patch-Clamp , Piperazinas/farmacologia , Piridinas/farmacologia , Proteínas de Ligação a RNA/genética , Ratos , Ratos Transgênicos , Ratos Wistar , Serotonina/farmacologia , Antagonistas da Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Estresse Psicológico/genética , Natação/psicologia , Transmissão Sináptica/genética , TransfecçãoRESUMO
Plant materials have long been demonstrated to sorb organic compounds. However, there are no known reports about pollen grains acting as sorbents to remove hydrophobic organic compounds (HOCs) such as pesticides, polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) from contaminated waters. We report a facile and effective method to remove HOCs from water using magnetized short ragweed (Ambrosia artemisiifolia) pollen grains. We dispersed the magnetized pollen grains in two different water samples - deionized (DI) and natural storm water to mimic real environmental conditions likely to be encountered during treatment. The magnetized pollen grains were readily separated from the aqueous media via a magnetic field after adsorption of the HOCs. We measured the adsorption of five representative HOCs (acenaphthene, phenanthrene, atrazine, diuron, and lindane) onto magnetized ragweed pollen in different aqueous matrices. We demonstrate that the adsorption capacity of the magnetized ragweed pollen can be regenerated to a large extent for reuse as a sorbent. Our results also indicate that the magnetized pollen grains are as effective as activated carbon (AC) in removing HOCs from both types of contaminated waters. The high HOC sorption of the ragweed pollen allows it to have potential remediation application in the field under realistic conditions.