Byline: Ijair. dos Santos, Michelle. Dias, Walace. Gomes-Leal
The discovery that new neurons are produced in some regions of the adult mammalian brain is a paradigm-shift in neuroscience research. These new-born cells are produced from neuroprogenitors mainly in the subventricular zone at the margin of the lateral ventricle, subgranular zone in the hippocampal dentate gyrus and in the striatum, a component of the basal ganglia, even in humans. In the human hippocampus, neuroblasts are produced even in elderlies. The regulation of adult neurogenesis is a complex phenomenon involving a multitude of molecules, neurotransmitters and soluble factors released by different sources including glial cells. Microglia, the resident macrophages of the central nervous system, are considered to play an important role on the regulation of adult neurogenesis both in physiological and pathological conditions. Following stroke and other acute neural disorders, there is an increase in the numbers of neuroblast production in the neurogenic niches. Microglial activation is believed to display both beneficial and detrimental role on adult neurogenesis after stroke, depending on the activation level and brain location. In this article, we review the scientific evidence addressing the role of microglial activation on adult neurogenesis after ischemia. A comprehensive understanding of the microglial role after stroke and other neural disorders it is an important step for development of future therapies based on manipulation of adult neurogenesis.
Adult Neurogenesis: Historical Background
There was a long-lasting belief that the central nervous system (CNS) of adult mammals was unable to generate new neurons. Nevertheless, the pioneering studies performed by Joseph Altman (Altman and Das, 1965), Michael Kaplan (Kaplan and Hinds, 1977) and Fernando Nottebohm (Nottebohm et al., 1986), respectively, in the 1960s, 1970s and 1980s were the basis for in vitro studies performed in the 1990s (Reynolds and Weiss, 1992) that definitively confirmed that the adult brain possesses the capacity of producing new neurons (Lima and Gomes-leal W, 2019). An important contribution to the field was the demonstration that new granule neurons are produced in the dentate gyrus (DG) of adult rodents (Cameron, 1994; Gould et al., 1997). Therefore, the neural circuits of adult mammalian brains are not fixed and immutable as previously thought. Experimental findings suggest that the brain modulates and maintains preexisting neural circuits by adding newborn cells (Vicidomini et al., 2020). In addition, this phenomenon might be used to replace neurons lost after CNS diseases (Zhao et al., 2008).
Nowadays, is fully confirmed the existence of two main neurogenic niches in the mammalian brain: subventricular zone (SVZ) at the wall of lateral ventricles (Doetsch et al., 1997) and subgranular zone in the hippocampus, even in humans (Boldrini et al., 2018; Moreno-Jimenez et al., 2019). In the SVZ, astrocyte-like adult neural stem cells, termed B1 in mice, generate C cells, which in turn generate neuroblasts (A cells). These immature neurons migrate to the olfactory bulb (OB) to be constantly integrated into preexisting neural circuits, which seems to be very important for maintenance and repair of OB circuitry (Imayoshi et al., 2008). In the...