RGD Reference Report - Beclin 1 knockdown inhibits autophagic activation and prevents the secondary neurodegenerative damage in the ipsilateral thalamus following focal cerebral infarction. - Rat Genome Database
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Beclin 1 knockdown inhibits autophagic activation and prevents the secondary neurodegenerative damage in the ipsilateral thalamus following focal cerebral infarction.

Authors: Xing, S  Zhang, Y  Li, J  Zhang, J  Li, Y  Dang, C  Li, C  Fan, Y  Yu, J  Pei, Z  Zeng, J 
Citation: Xing S, etal., Autophagy. 2012 Jan;8(1):63-76. doi: 10.4161/auto.8.1.18217. Epub 2012 Jan 1.
RGD ID: 11561900
Pubmed: (View Article at PubMed) PMID:22108007
DOI: Full-text: DOI:10.4161/auto.8.1.18217

Cerebral infarction can cause secondary degeneration of thalamus and delay functional recovery. However, the mechanisms underlying secondary degeneration are unclear. The present study aimed to determine the occurrence and contribution of autophagy to the thalamic degeneration after cerebral infarction. Focal cerebral infarction was induced by distal middle cerebral artery occlusion (MCAO). Autophagic activation, Beclin 1 expression and amyloid beta (Abeta) deposits were determined by immunofluorescence, immunoblot and electron microscopy. Secondary damage to thalamus was assessed with Nissl staining and immunofluorescence analysis. Apoptosis was determined using TUNEL staining. The contribution of autophagy to the secondary damage was evaluated by shRNA-mediated downregulation of Beclin 1 and the autophagic inhibitor, 3-methyladenine (3-MA). The potential role of Abeta in autophagic activation was determined with N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). The results showed that the conversion of LC3-II, the formation of autophagosomes, and the levels of activated cathepsin B and Beclin 1 were significantly increased in the ipsilateral thalamus at 7 and 14 days after MCAO (p < 0.05 or 0.01). Both Beclin 1 knockdown and 3-MA treatment significantly reduced LC3-II conversion and autophagosome formation, which were accompanied by obvious decreases in neuronal loss, gliosis and apoptosis in the ipsilateral thalamus (p < 0.05 or 0.01). Additionally, DAPT treatment markedly reduced Abeta deposits, which coincided with decreases in LC3-II conversion and autophagosome formation (p < 0.01). These results suggest that inhibition of autophagy by Beclin 1 knockdown can attenuate the secondary thalamic damage after focal cerebral infarction. Furthermore, Abeta deposits may be involved in the activation of autophagy.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Becn1  (beclin 1)

Genes (Mus musculus)
Becn1  (beclin 1, autophagy related)

Genes (Homo sapiens)
BECN1  (beclin 1)


Additional Information