Regional Microglial Response in Entorhino-Hippocampal Slice Cultures to Schaffer Collateral Lesion and Metalloproteinases Modulation

Microglia and astrocytes are essential in sustaining physiological networks in the central nervous system, with their ability to remodel the extracellular matrix, being pivotal for synapse plasticity. Recent findings have challenged the traditional view of homogenous glial populations in the brain, uncovering morphological, functional, and molecular heterogeneity among glial cells. This diversity has significant implications for both physiological and pathological brain states. In the present study, we mechanically induced a Schaffer collateral lesion (SCL) in mouse entorhino-hippocampal slice cultures to investigate glial behavior, i.e., microglia and astrocytes, under metalloproteinases (MMPs) modulation in the lesioned area, CA3, and the denervated region, CA1. We observed distinct response patterns in the microglia and astrocytes 3 days after the lesion. Notably, GFAP-expressing astrocytes showed no immediate changes post-SCL. Microglia responses varied depending on their anatomical location, underscoring the complexity of the hippocampal neuroglial network post-injury. The MMPs inhibitor GM6001 did not affect microglial reactions in CA3, while increasing the number of Iba1-expressing cells in CA1, leading to a withdrawal of their primary branches. These findings highlight the importance of understanding glial regionalization following neural injury and MMPs modulation and pave the way for further research into glia-targeted therapeutic strategies for neurodegenerative disorders.