A Microglial Function for the Nerve Growth Factor: Predictions of the Unpredictable

Microglia are the only immune cell population present in the brain parenchyma. Their vantage position in the central nervous system (CNS) enables these myeloid cells to perform the most disparate of tasks: from the classical immune functions of fighting infections and surveilling the extracellular space for pathogens and damage, to sculpting the neuronal circuitry by pruning unnecessary synapses and assisting neurons in spine formation, aiding in the maintenance of brain homeostasis. The neurotrophin field has always been dominated by the neurocentric view that the primary target of these molecules must be neurons: this holds true even for the Nerve Growth Factor (NGF), which owes its popularity in the neuroscience community to its trophic and tropic activity towards sensory and sympathetic neurons in the peripheral nervous system, and cholinergic neurons in the CNS. The increasing evidence that microglia are an integral part of neuronal computation calls for a closer look as to whether these glial cells are capable of responding directly to NGF. In this review, we will first outline evidence in support of a role for NGF as a molecule mediating neuroimmune communication. Then, we will illustrate some of those non-immune features that have made microglial cells one of the hottest topics of this last decade. In conclusion, we will discuss evidence in support of a microglial function for NGF.