The neuron-astrocyte-microglia triad involvement in neuroinflammaging mechanisms in the CA3 hippocampus of memory-impaired aged rats.

ABSTRACT

We examined the effects of inflammaging on memory encoding, and qualitative and quantitative modifications on proinflammatory proteins, apoptosis, neurodegeneration and morphological changes of neuron-astrocyte-microglia triads in CA3 Stratum Pyramidale (SP), Stratum Lucidum (SL) and Stratum Radiatum (SR) of young (3months) and aged rats (20months). Aged rats showed short-term memory impairments in the inhibitory avoidance task, increased expression of iNOS and activation of p38MAPK in SP, increase of apoptotic neurons in SP and of ectopic neurons in SL, and decrease of CA3 pyramidal neurons. The number of astrocytes and their branches length decreased in the three CA3 subregions of aged rats, with morphological signs of clasmatodendrosis. Total and activated microglia increased in the three CA3 subregions of aged rats. In aged rats CA3, astrocytes surrounded ectopic degenerating neurons forming "micro scars" around them. Astrocyte branches infiltrated the neuronal cell body, and, together with activated microglia formed "triads". In the triads, significantly more numerous in CA3 SL and SR of aged rats, astrocytes and microglia cooperated in fragmentation and phagocytosis of ectopic neurons. Inflammaging-induced modifications of astrocytes and microglia in CA3 of aged rats may help clearing neuronal debris derived from low-grade inflammation and apoptosis. These events might be common mechanisms underlying many neurodegenerative processes. The frequency to which they appear might depend upon, or might be the cause of, the burden and severity of neurodegeneration. Targeting the triads may represent a therapeutic strategy which may control inflammatory processes and spread of further cellular damage to neighboring cells.