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1.
Genes Brain Behav ; 20(7): e12755, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34056840

RESUMO

While there is a strong focus on the negative consequences of maternal immune activation (MIA) on developing brains, very little attention is directed towards potential advantages of early life challenges. In this study, we utilized a polyinosine-polycytidylic acid (poly(I:C)) MIA model to test visual pairwise discrimination (PD) and reversal learning (RL) in mice using touchscreen technology. Significant sex differences emerged in that MIA reduced the latency for males to make a correct choice in the PD task while females reached criterion sooner, made fewer errors, and utilized fewer correction trials in RL compared to saline controls. These surprising improvements were accompanied by the sex-specific upregulation of several genes critical to cognitive functioning, indicative of compensatory plasticity in response to MIA. In contrast, when exposed to a 'two-hit' stress model (MIA + loss of the social component of environmental enrichment [EE]), mice did not display anhedonia but required an increased number of PD and RL correction trials. These animals also had significant reductions of CamK2a mRNA in the prefrontal cortex. Appropriate functioning of synaptic plasticity, via mediators such as this protein kinase and others, are critical for behavioral flexibility. Although EE has been implicated in, delaying the appearance of symptoms associated with certain brain disorders, these findings are in line with evidence that it also makes individuals more vulnerable to its loss. Overall, with the right 'dose', early life stress exposure can confer at least some functional advantages, which are lost when the number or magnitude of these exposures become too great.


Assuntos
Discriminação Psicológica/efeitos dos fármacos , Poli I-C/farmacologia , Reversão de Aprendizagem/efeitos dos fármacos , Fatores Sexuais , Percepção Visual/imunologia , Animais , Atenção/efeitos dos fármacos , Comportamento Animal/fisiologia , Cognição/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Camundongos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/imunologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Percepção Visual/efeitos dos fármacos , Percepção Visual/fisiologia
2.
J Neurotrauma ; 37(12): 1463-1480, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32056479

RESUMO

The purpose of this study was to characterize acute changes in inflammatory pathways in the mouse eye after blast-mediated traumatic brain injury (bTBI) and to determine whether modulation of these pathways could protect the structure and function of retinal ganglion cells (RGC). The bTBI was induced in C57BL/6J male mice by exposure to three 20 psi blast waves directed toward the head with the body shielded, with an inter-blast interval of one hour. Acute cytokine expression in retinal tissue was measured through reverse transcription-quantitative polymerase chain reaction (RT-qPCR) four hours post-blast. Increased retinal expression of interleukin (lL)-1ß, IL-1α, IL-6, and tumor necrosis factor (TNF)α was observed in bTBI mice exposed to blast when compared with shams, which was associated with activation of microglia and macroglia reactivity, assessed via immunohistochemistry with ionized calcium binding adaptor molecule 1 and glial fibrillary acidic protein, respectively, one week post-blast. Blockade of the IL-1 pathway was accomplished using anakinra, an IL-1RI antagonist, administered intra-peritoneally for one week before injury and continuing for three weeks post-injury. Retinal function and RGC layer thickness were evaluated four weeks post-injury using pattern electroretinogram (PERG) and optical coherence tomography (OCT), respectively. After bTBI, anakinra treatment resulted in a preservation of RGC function and RGC structure when compared with saline treated bTBI mice. Optic nerve integrity analysis demonstrated a trend of decreased damage suggesting that IL-1 blockade also prevents axonal damage after blast. Blast exposure results in increased retinal inflammation including upregulation of pro-inflammatory cytokines and activation of resident microglia and macroglia. This may explain partially the RGC loss we observed in this model, as blockade of the acute inflammatory response after injury with the IL-1R1 antagonist anakinra resulted in preservation of RGC function and RGC layer thickness.


Assuntos
Lesões Encefálicas Traumáticas/imunologia , Imunidade/imunologia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Receptores de Interleucina-1/antagonistas & inibidores , Retina/imunologia , Percepção Visual/imunologia , Animais , Traumatismos por Explosões/diagnóstico por imagem , Traumatismos por Explosões/tratamento farmacológico , Traumatismos por Explosões/imunologia , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/tratamento farmacológico , Eletrorretinografia/métodos , Imunidade/efeitos dos fármacos , Proteína Antagonista do Receptor de Interleucina 1/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Retina/diagnóstico por imagem , Retina/efeitos dos fármacos , Tomografia de Coerência Óptica/métodos , Resultado do Tratamento , Percepção Visual/efeitos dos fármacos
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