Transgenic mouse models for studying adult neurogenesis

Abstract

The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life. Newborn neurons, generated by the radial neural stem cells (NSCs), are important for learning and memory as well as mood control. During aging, the number and responses of NSCs to neurogenic stimuli diminish, leading to decreased neurogenesis and age-associated cognitive decline and psychiatric disorders. Thus, adult hippocampal neurogenesis has garnered significant interest because targeting it could be a novel potential therapeutic strategy for these disorders. However, if we are to use neurogenesis to halt or reverse hippocampal-related pathology, we need to understand better the core molecular machinery that governs NSC and their progeny. In this review, we summarize a wide variety of mouse models used in adult neurogenesis field, present their advantages and disadvantages based on specificity and efficiency of labeling of different cell types, and review their contribution to our understanding of the biology and the heterogeneity of different cell types found in adult neurogenic niches.

Keywords: adult neurogenesis; lineage tracing; mouse models; neural stem cells; neuroprogenitors.

Figure 1. Summary of immunohistochemical markers, reporter and lineage tracing mouse models used to identify different cell types of the adult hippocampal neurogenic niche

NSC, neural stem cells; RGL, radial glia like cells; ANP, amplifying neuroprogenitors; IPC, intermediate progenitor cells. Upper part: Markers, Middle part: Reporter lines; Lower part: Lineage tracing lines. * denotes the mouse models that target mostly quiescent neural stem cells

Figure 2. Summary of immunohistochemical markers, reporter and lineage tracing mouse models used to identify different cell types of the adult subventricular zone neurogenic niche

Broken strip (EGFR) indicates expression in only subset of Type B cells. EGFR⁺ population is actively cycling whereas EGFR⁻ population consists of quiescent SVZ neural stem cells. SVZ=subventricular zone; RMS=rostral migratory stream; OB=olfactory bulb. Upper part: Markers, Middle part: Reporter lines; Lower part: Lineage tracing lines.