RESUMEN
Monocyte-derived macrophages play a role in the repair of the injured brain. We previously reported that a deficiency of the Parkinson's disease (PD)-associated gene DJ-1 delays repair of brain injury produced by stereotaxic injection of ATP, a component of damage-associated molecular patterns. Here, we show that a DJ-1 deficiency attenuates monocyte infiltration into the damaged brain owing to a decrease in C-C motif chemokine ligand 2 (CCL2) expression in astrocytes. Like DJ-1-knockout (KO) mice, CCL2 receptor (CCR2)-KO mice showed defects in monocyte infiltration and delayed recovery of brain injury, as determined by 9.4 T magnetic resonance imaging analysis and immunostaining for tyrosine hydroxylase and glial fibrillary acid protein. Notably, transcriptome analyses showed that genes related to regeneration and synapse formation were similarly downregulated in injured brains of DJ-1-KO and CCR2-KO mice compared with the injured wild-type brain. These results indicate that defective astrogliosis in DJ-1-KO mice is associated with decreased CCL2 expression and attenuated monocyte infiltration, resulting in delayed repair of brain injury. Thus, delayed repair of brain injury could contribute to the development of PD. MAIN POINTS: A DJ-1 deficiency attenuates infiltration of monocytes owing to a decrease in CCL2 expression in astrocytes, which in turn led to delay in repair of brain injury.
Asunto(s)
Astrocitos/metabolismo , Lesiones Encefálicas/metabolismo , Quimiocina CCL2/biosíntesis , Monocitos/metabolismo , Proteína Desglicasa DJ-1/deficiencia , Animales , Astrocitos/patología , Lesiones Encefálicas/genética , Lesiones Encefálicas/patología , Quimiocina CCL2/antagonistas & inhibidores , Quimiocina CCL2/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Monocitos/patología , Proteína Desglicasa DJ-1/genéticaRESUMEN
In this study, we examined how systemic inflammation affects repair of brain injury. To this end, we created a brain-injury model by stereotaxic injection of ATP, a damage-associated molecular pattern component, into the striatum of mice. Systemic inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS-ip). An analysis of magnetic resonance images showed that LPS-ip reduced the initial brain injury but slowed injury repair. An immunostaining analysis using the neuronal marker, NeuN, showed that LPS-ip delayed removal of dead/dying neurons, despite the fact that LPS-ip enhanced infiltration of monocytes, which serve to phagocytize dead cells/debris. Notably, infiltrating monocytes showed a widely scattered distribution. Bulk RNAseq analyses showed that LPS-ip decreased expression of genes associated with phagocytosis, with PCR and immunostaining of injured brains confirming reduced levels of Cd68 and Clec7a, markers of phagocytic activity, in monocytes. Collectively, these results suggest that systemic inflammation affects properties of blood monocytes as well as brain cells, resulting in delay in clearing damaged cells and activating repair processes.
Asunto(s)
Encéfalo , Inflamación , Lipopolisacáridos , Ratones Endogámicos C57BL , Monocitos , Fagocitosis , Animales , Fagocitosis/efectos de los fármacos , Monocitos/metabolismo , Inflamación/patología , Encéfalo/patología , Masculino , Lipopolisacáridos/farmacología , Lesiones Encefálicas/patología , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Neuronas/metabolismo , Neuronas/patología , Neuronas/efectos de los fármacos , Lectinas Tipo C/metabolismo , Cicatrización de Heridas , Ratones , Adenosina Trifosfato/metabolismo , Molécula CD68RESUMEN
Queensland fruit fly (Q-fly), Bactrocera tryoni (Froggatt), presents a major threat to Australian fruit production and trade. The sterile insect technique (SIT) is increasingly employed to manage Q-fly. Quality of sterile males released in SIT programs, and hence program efficacy, can be affected by pre- and post-production processes, such as mass rearing, packing, irradiation, transportation, and release. Given long distances from rear-out facilities to release sites, adult flies are usually chilled to reduce metabolism and stress during transportation. To guide SIT procedures, it is important to understand the impact of such practices on performance of sterile Q-fly. The present study assesses the effect of chilling temperature and exposure period on quality parameters of sterile Q-fly. We considered the effects of two temperature regimes (4 and 6°C) and six exposure periods (0, 1, 2, 4, 6, and 12 h) on chill-coma recovery time, flight ability, survival under nutritional stress, and longevity of both males and females. Flies chilled at 4°C took longer to recover than that those chilled at 6°C. Flight ability, survival under nutritional stress, and longevity all decreased as chilling period increased but did not differ between the two tested temperatures. We recommend that periods of chilling during transportation from rear-out facilities to release sites be minimized in order to retain quality of sterile Q-fly and that increased release rates be considered when longer chilling periods are required.