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1.
Mater Sci Eng C Mater Biol Appl ; 107: 110325, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761222

RESUMO

Synthesis of nanomaterials having uniform shape and size is a challenging task. Properties exhibited by such substrates would be compatible and homogeneous compared to the average properties displayed by those substrates with heterogeneous size. Herein, we report the synthesis of polypyrrole nanorods (PPy-NRs) of almost uniform size via oxidative chemical polymerization of pyrrole within anodized aluminum oxide nanopores followed by sacrificial removal of the template. Field emission scanning electron microscopy (FE-SEM), fourier transformed infra-red (FT-IR) spectra, X-ray diffraction (XRD), and ultra-violet-visible-near infra-red (UV-Vis-NIR) spectra of the substrate were used to analyze the physicochemical properties of as-synthesized PPy-NRs. PPy-NRs treated MC3T3-E1 and PC12 cells exhibited good biocompatibility in CCK-8 and live/dead assays. The assay showed more cell viability on PC12 cell lines. Electrical stimulation through PPy-NRs treated PC12 cells accelerated neuronal differentiation compared to those without electrical stimulation during in vitro cell culture.


Assuntos
Nanoporos , Nanotubos/química , Neurônios/efeitos dos fármacos , Polímeros/síntese química , Polímeros/farmacologia , Pirróis/síntese química , Pirróis/farmacologia , Óxido de Alumínio/isolamento & purificação , Animais , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular , Estimulação Elétrica , Camundongos , Microscopia Eletrônica de Varredura , Neurônios/fisiologia , Osteoblastos/efeitos dos fármacos , Células PC12 , Polimerização , Ratos , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
2.
Nat Med ; 23(1): 39-48, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27892953

RESUMO

Although 22q11.2 deletion syndrome (22q11DS) is associated with early-life behavioral abnormalities, affected individuals are also at high risk for the development of schizophrenia symptoms, including psychosis, later in life. Auditory thalamocortical (TC) projections recently emerged as a neural circuit that is specifically disrupted in mouse models of 22q11DS (hereafter referred to as 22q11DS mice), in which haploinsufficiency of the microRNA (miRNA)-processing-factor-encoding gene Dgcr8 results in the elevation of the dopamine receptor Drd2 in the auditory thalamus, an abnormal sensitivity of thalamocortical projections to antipsychotics, and an abnormal acoustic-startle response. Here we show that these auditory TC phenotypes have a delayed onset in 22q11DS mice and are associated with an age-dependent reduction of miR-338-3p, a miRNA that targets Drd2 and is enriched in the thalamus of both humans and mice. Replenishing depleted miR-338-3p in mature 22q11DS mice rescued the TC abnormalities, and deletion of Mir338 (which encodes miR-338-3p) or reduction of miR-338-3p expression mimicked the TC and behavioral deficits and eliminated the age dependence of these deficits. Therefore, miR-338-3p depletion is necessary and sufficient to disrupt auditory TC signaling in 22q11DS mice, and it may mediate the pathogenic mechanism of 22q11DS-related psychosis and control its late onset.


Assuntos
Córtex Auditivo/fisiopatologia , Vias Auditivas/fisiopatologia , Síndrome de DiGeorge/genética , MicroRNAs/genética , Transtornos Psicóticos/genética , Tálamo/fisiopatologia , Idade de Início , Animais , Antipsicóticos/farmacologia , Córtex Auditivo/efeitos dos fármacos , Córtex Auditivo/metabolismo , Vias Auditivas/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Western Blotting , Síndrome de DiGeorge/fisiopatologia , Síndrome de DiGeorge/psicologia , Modelos Animais de Doenças , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Potenciais Evocados Auditivos do Tronco Encefálico/genética , Deleção de Genes , Haploinsuficiência , Humanos , Camundongos , MicroRNAs/metabolismo , Vias Neurais , Optogenética , Técnicas de Patch-Clamp , Fenótipo , Transtornos Psicóticos/fisiopatologia , Transtornos Psicóticos/psicologia , Proteínas de Ligação a RNA/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Dopamina D2/genética , Reflexo de Sobressalto , Esquizofrenia/metabolismo , Tálamo/efeitos dos fármacos , Tálamo/metabolismo
3.
Science ; 344(6188): 1178-82, 2014 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-24904170

RESUMO

Auditory hallucinations in schizophrenia are alleviated by antipsychotic agents that inhibit D2 dopamine receptors (Drd2s). The defective neural circuits and mechanisms of their sensitivity to antipsychotics are unknown. We identified a specific disruption of synaptic transmission at thalamocortical glutamatergic projections in the auditory cortex in murine models of schizophrenia-associated 22q11 deletion syndrome (22q11DS). This deficit is caused by an aberrant elevation of Drd2 in the thalamus, which renders 22q11DS thalamocortical projections sensitive to antipsychotics and causes a deficient acoustic startle response similar to that observed in schizophrenic patients. Haploinsufficiency of the microRNA-processing gene Dgcr8 is responsible for the Drd2 elevation and hypersensitivity of auditory thalamocortical projections to antipsychotics. This suggests that Dgcr8-microRNA-Drd2-dependent thalamocortical disruption is a pathogenic event underlying schizophrenia-associated psychosis.


Assuntos
Síndrome da Deleção 22q11/genética , Córtex Auditivo/metabolismo , Haploinsuficiência , Proteínas de Ligação a RNA/genética , Receptores de Dopamina D2/biossíntese , Esquizofrenia/genética , Tálamo/metabolismo , Síndrome da Deleção 22q11/tratamento farmacológico , Animais , Antipsicóticos/uso terapêutico , Modelos Animais de Doenças , Resistência a Medicamentos/genética , Camundongos , Camundongos Mutantes , MicroRNAs/metabolismo , Receptores de Dopamina D2/genética , Esquizofrenia/tratamento farmacológico , Transmissão Sináptica/genética
4.
J Neurosci ; 33(17): 7345-57, 2013 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-23616541

RESUMO

Cortical maps in sensory cortices are plastic, changing in response to sensory experience. The cellular site of such plasticity is currently debated. Thalamocortical (TC) projections deliver sensory information to sensory cortices. TC synapses are currently dismissed as a locus of cortical map plasticity because TC synaptic plasticity is thought to be limited to neonates, whereas cortical map plasticity can be induced in both neonates and adults. However, in the auditory cortex (ACx) of adults, cortical map plasticity can be induced if animals attend to a sound or receive sounds paired with activation of cholinergic inputs from the nucleus basalis. We now show that, in the ACx, long-term potentiation (LTP), a major form of synaptic plasticity, is expressed at TC synapses in both young and mature mice but becomes gated with age. Using single-cell electrophysiology, two-photon glutamate uncaging, and optogenetics in TC slices containing the auditory thalamus and ACx, we show that TC LTP is expressed postsynaptically and depends on group I metabotropic glutamate receptors. TC LTP in mature ACx can be unmasked by cortical disinhibition combined with activation of cholinergic inputs from the nucleus basalis. Cholinergic inputs passing through the thalamic radiation activate M1 muscarinic receptors on TC projections and sustain glutamate release at TC synapses via negative regulation of presynaptic adenosine signaling through A1 adenosine receptors. These data indicate that TC LTP in the ACx persists throughout life and therefore can potentially contribute to experience-dependent cortical map plasticity in the ACx in both young and adult animals.


Assuntos
Córtex Auditivo/fisiologia , Período Crítico Psicológico , Potenciação de Longa Duração/fisiologia , Plasticidade Neuronal/fisiologia , Tálamo/fisiologia , Fatores Etários , Animais , Animais Recém-Nascidos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Técnicas de Cultura de Órgãos
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