Suppression of neuroinflammation in forebrain-specific Cdk5 conditional knockout mice by PPARγ agonist improves neuronal loss and early lethality.

ABSTRACT:

Background

Cyclin-dependent kinase 5 (Cdk5) is essential for brain development and function, and its deregulated expression is implicated in some of neurodegenerative diseases. We reported earlier that the forebrain-specific Cdk5 conditional knockout (cKO) mice displayed an early lethality associated with neuroinflammation, increased expression of the neuronal tissue-type plasminogen activator (tPA), and neuronal migration defects.

Methods

In order to suppress neuroinflammation in the cKO mice, we first treated these mice with pioglitazone, a PPARγ agonist, and analyzed its effects on neuronal loss and longevity. In a second approach, to delineate the precise role of tPA in neuroinflammation in these mice, we generated Cdk5 cKO; tPA double knockout (dKO) mice.

Results

SUBMITTER: Utreras E 

PROVIDER: S-EPMC3931315 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature