engleski

Impact of Toll –like receptor 2 on hippocampal neurogenesis and cognitive function in adult mice

In the adult central nervous system (CNS), ongoing neurogenesis persists in two regions, the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG). Newly born neurons generated from neural stem and progenitor cells in the DG integrate locally into the granular layer of the DG as granule cells, which contribute to learning and memory. However, the precise molecular mechanisms involved in the regulation of neurogenesis are still not fully defined. Toll- like receptors (TLRs) are innate immune receptors that prime an inflammatory response and facilitate activation of the adaptive immune response. In addition, recently TLRs have emerged as regulators of multiple processes in the CNS such as neuronal survival, axonal growth, and synaptic plasticity. Thus TLR2, widely expressed within the CNS, is found to be expressed in neural progenitor cells (NPCs) as well. It has been shown that TLR2 expressed by these cells is involved in their differentiation into neurons. In this study, using adult TLR2 deficient mice and their wild- type littermates, we investigated the impact of TLR2 on hippocampal neurogenesis and cognitive function. TLR2 deficiency does not alter the proliferative capacity of NPC in the dentate gyrus, but affects their phenotypic fate by increasing the formation of astrocytes at the expense of neurons. Furthermore, TLR2 deficient mice exhibit reduced dendritic arborization and performed significantly worse in hippocampal- dependent behavioral tasks compared to their control littermates. Thus, our data indicate that dysregulation of the innate immune system by a TLR2 deficiency impairs neurogenesis in the hippocampal DG and cognitive function in adult mice.

Toll-like receptor 2 ; hippocampal neurogenesis, cognitive function, mice

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