Genetic deletion of neuronal pentraxin 1 expression prevents brain injury in a neonatal mouse model of cerebral hypoxia-ischemia.

Genetic deletion of neuronal pentraxin 1 expression prevents brain injury in a neonatal mouse model of cerebral hypoxia-ischemia. Neurobiol Dis. 2014 Dec 29; Authors: Thatipamula S, Rahim MA, Zhang J, Hossain MA Abstract Neonatal hypoxic-ischemic (HI) brain injury is a leading cause of mortality and morbidity in infants and children for which there is no promising therapy at present. Previously, we reported induction of neuronal pentraxin 1 (NP1), a novel neuronal protein of the long-pentraxin family, following HI injury in neonatal brain. Here, we report that genetic deletion of NP1 expression prevents HI injury in neonatal brain. Elevated expression of NP1 was observed in neurons, not in astrocytes, of the ipsilateral cortical layers (I-IV) and in the hippocampal CA1 and CA3 areas of WT brains following hypoxia-ischemia; brain areas that developed infarcts (at 24-48h), showed significantly increased number of TUNEL-(+) cells and tissue loss (at 7 d). In contrast, NP1-KO mice showed no evidence of brain infarction and tissue loss after HI. The immunofluorescence staining of brain sections with mitochondrial protein COX IV and subcellular fractionation analysis showed increased accumulation of NP1 in mitochondria, pro-death protein Bax activation and NP1co-localization with activated caspase-3 in WT, but not in the NP1-KO brains; corroborating NP1 interactions with the mitochondria-derived pro-death pathways. Disruption of NP1 transl...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research