MT5-MMP promotes neuroinflammation, neuronal excitability and Aβ production in primary neuron/astrocyte cultures from the 5xFAD mouse model of Alzheimer's disease.

ABSTRACT:

Background

Membrane-type matrix metalloproteinase 5 (MT5-MMP) deficiency in the 5xFAD mouse model of Alzheimer's disease (AD) reduces brain neuroinflammation and amyloidosis, and prevents deficits in synaptic activity and cognition in prodromal stages of the disease. In addition, MT5-MMP deficiency prevents interleukin-1 beta (IL-1β)-mediated inflammation in the peripheral nervous system. In this context, we hypothesized that the MT5-MMP/IL-1β tandem could regulate nascent AD pathogenic events in developing neural cells shortly after the onset of transgene activation.

Methods

To test this hypothesis, we used 11-14 day in vitro primary cortical cultures from wild type, MT5-MMP^-/-, 5xFAD and 5xFAD/MT5-MMP^-/- mice, and evaluated the impact of MT5-MMP defic

SUBMITTER: Pilat D 

PROVIDER: S-EPMC8915472 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature