Regional Microglial Response in Enthorino-hippocampal Slice Cultures to Schaffer Collateral Lesion and Metalloproteinases Modulation

Abstract

Microglia and astrocytes are essential in sustaining physiological networks on the central nervous system, with their ability to remodel the extracellular matrix, being pivotal for synapse plasticity. Recent findings challenge the traditional view of homogenous glial populations in the brain, uncovering morphological, functional and molecular heterogeneity among glial cells. This di-versity has significant implications for both physiological and pathological brain states. In the present study, we mechanically induced a Schaffer collateral lesion (SCL) in mouse enthori-no-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 microglia and astrocytes 3 days after the lesion. Notably, GFAP-expressing astrocytes showed no immediate changes post-SCL. Microglia re-sponses varied depending on their anatomical location. The MMPs inhibitor GM6001 did not affect microglial reactions in CA3, while increasing the Iba1 cells numbers in CA1, underscoring the complexity of the hippocampal neuroglial network post-injury. 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 neurodegen-erative disorders.