Abstract
Neuronal activity is closely influenced by glia, especially microglia which are the resident immune cells in the central nervous system (CNS). Microglia in medicinal leech are the only cells able to migrate to the injury site within the 24 hours post-lesion. The microglia-neuron interactions constitute an important mechanism as there is neither astrocyte nor oligodendrocyte in the leech CNS. Given that axonal sprouting is impaired when microglia recruitment is inhibited, the crosstalk between microglia and neurons plays a crucial role in neuroprotection. The present results show that neurons and microglia both use ALK4/5 (a type of TGF-β receptor) signaling in order to maintain mutual exchanges in an adult brain following an axonal injury. Indeed, a TGF-β family member (nGDF) is immediately released by injured axons contributing to the early recruitment of ALK4/5+ microglia to the lesion site. Surprisingly, within the following hours, nGDF from microglia activates ALK4/5+ neurons to maintain a later microglia accumulation in lesion. Taken together, the results demonstrate that ALK4/5 signaling is essential throughout the response to the lesion in the leech CNS and gives a new insight in the understanding of this pathway. This latter is an important signal contributing to a correct sequential mobilization over time of microglia recruitment leading to axon regeneration.
Highlights
The nerve cord from the medicinal leech (Hirudo medicinalis) is an excellent model in this regard
Because the results showed the involvement of the ALK4/5 pathway in the crosstalk between microglia and neurons, the protein profiles throughout the microglia recruitment were studied in the lesion site using a Liquid Extraction Surface Analysis (LESA) approach
A similar observation is performed between microglia and peritoneal macrophages demonstrating a preferential expression of mRNAs encoding TGF-β receptors tgfbr[1] and tgfbr[2] in microglia[22]
Summary
The nerve cord from the medicinal leech (Hirudo medicinalis) is an excellent model in this regard. Microglial cells are positive for iba[1] marker as its mammalian counterparts They progressively change their morphology from ramified to an amoeboid shape so that they move to the lesion without any blood cell infiltration[7,8]. Microglia in leech are the only cells able to migrate to an injury site (Fig. 1) depending on chemotactic signals including ATP, C1q, EMAPII and Interleukin-1612–17. This recruitment massively occurs within the 24 hours post-lesion[18,19]. We use an axonal lesion system in the connectives of the leech CNS It involves the recruitment of microglia subpopulations over time. After the characterization of a TGF-β type I receptor in the leech microglia and neurons, its involvement in the time-course of microglia recruitment was evaluated following the axonal lesion
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