RGD Reference Report - Inhibition of NF-kappaB activation by Pyrrolidine dithiocarbamate partially attenuates hippocampal MMP-9 activation and improves cognitive deficits in streptozotocin-induced diabetic rats. - Rat Genome Database

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Inhibition of NF-kappaB activation by Pyrrolidine dithiocarbamate partially attenuates hippocampal MMP-9 activation and improves cognitive deficits in streptozotocin-induced diabetic rats.

Authors: Zhao, Z  Huang, G  Wang, B  Zhong, Y 
Citation: Zhao Z, etal., Behav Brain Res. 2013 Feb 1;238:44-7. doi: 10.1016/j.bbr.2012.10.018. Epub 2012 Oct 23.
RGD ID: 8547974
Pubmed: PMID:23089644   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbr.2012.10.018   (Journal Full-text)

Matrix metalloproteinase-9 (MMP-9) has been found at significantly increased activity and also contributes to blood-brain barrier degradation in diabetes. Activation of NF-kappaB pathway is associated with diabetes-induced cognitive impairment, and MMP-9 gene promoter contains a highly conserved motif that matches the NF-kappaB p65 binding element. No data have been yet provided to show that diabetes-induced cognitive decline is actually associated with increased activity of MMP-9, however, so we sought to understand the potential role of NF-kappaB-MMP-9 pathway in diabetic rats' brain. Streptozocin (STZ) was used to induce diabetes in Wistar rats. Pyrrolidine dithiocarbamate (PDTC), an effective NF-kappaB inhibitor, was administrated to diabetic rats for 6 weeks from the end of diabetes induction. Six weeks later, separate cohorts of rats were tested for cognitive function with Morris water maze task, or euthanized to assess MMP-9 and NF-kappaB levels in hippocampus. The diabetic rats developed cognitive deficit which was associated with enhanced hippocampal MMP-9 and NF-kappaB expression. PDTC treatment returned the levels of NF-kappaB toward their control values and significantly improved diabetes-induced behavioral dysfunction. However, the hippocampal MMP-9 expression triggered by diabetes was only slightly (though significantly) attenuated because MMP-9 protein level in PDTC treated diabetic rats was still higher than that in control rats. Moreover, chronic PDTC treatment did not affect the body weight and plasma glucose levels as compared to the diabetic group, which suggested that PDTC could not ameliorate the diabetic metabolic disorder. In conclusion, these data reveal that diabetes-associated cognitive deficit stems partially from up-regulation of hippocampal MMP-9 via activation of NF-kappaB signaling pathway.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus treatmentISOMmp9 (Rattus norvegicus)8547974; 8547974 RGD 
Experimental Diabetes Mellitus treatmentIEP 8547974 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mmp9  (matrix metallopeptidase 9)

Genes (Mus musculus)
Mmp9  (matrix metallopeptidase 9)

Genes (Homo sapiens)
MMP9  (matrix metallopeptidase 9)


Additional Information