Neurogenesis after neuron loss. (a) Spontaneous neuronal regeneration in HD. In parallel with the progressive degeneration of striatal neurons caused by HD, the production of new neurons in the SVZ increases significantly. These new neurons migrate into the affected striatum, where only some differentiate into mature neurons. (b) Migration of new neurons toward the damaged area in the mouse MCAO model. MCAO causes an infarction in the striatum and adjacent parietal cortex. Within a week of the insult, neural stem cells (blue) and transit-amplifying cells (green) in the SVZ begin to proliferate, and by two or three weeks after MCAO, new neurons (red) migrate and appear at the border of the damaged area in the striatum. (c) At left, a schematic drawing of the coronal brain section 18 days after MCAO. At right a section immunostained for DCX. Boxed area is shown at higher magnification at far right. Many new neurons migrate into the ipsilateral striatum, but not the contralateral striatum. Some new neurons migrate into the striatum in chain-like clusters (far right, arrowheads). Scale bars: left, 500 μm; right, 200 μm. (d) Schematic drawing of new neurons migrating along blood vessels toward the damaged striatum. (e) Confocal projection image of new neurons migrating along blood vessels, in a coronal brain section, 18 days after MCAO. The section was immunostained for DCX (green) and an endothelial cell marker, PECAM-1 (red). Scale bar: 50 μm. MCAO, middle cerebral artery occlusion; SVZ, subventricular zone; OB, olfactory bulb; DCX, doublecortin; PECAM-1, platelet endothelial cell adhesion molecule-1.

Neurogenesis in the adult brain. (a) Schematic drawing of adult rodent brain showing the two regions, the SVZ and the DG, where new neurons are continuously generated. (b) Location and structure of the SVZ. The SVZ consists of four types of cells, ependymal cells (purple), neural stem cells (blue), transit-amplifying cells (green), and new neurons (red). Neural stem cells directly contact the ventricle with their apical membrane and extend long basal processes that end on blood vessels within the ventricular wall. The neural stem cell proliferates slowly to replicate itself (self-renewal) and to generate transit-amplifying cells. Transit-amplifying cells proliferate quickly, and the progeny differentiate into immature new neurons. (c) Migration of new neurons. New neurons generated in the SVZ migrate into the OB through the RMS, where they form elongated chain-like cell aggregates, which are surrounded by astrocytic tunnels, called glial tubes. The new neurons (red) in the RMS secrete Slit1, whose receptor, Robo, is expressed on astrocytes (blue). Through the Slit1-Robo pathway, the new neurons regulate the morphology of the astrocytes, promoting the formation and maintenance of the glial tubes, which are needed for the neurons' rapid and directional migration. (d) Differentiation of new neurons in the OB. New neurons (red) that reach the OB detach from the chain and migrate radially toward their final destinations, where they differentiate into two types of olfactory interneurons, granule cells (pink) and periglomerular cells (orange) in different layers, the GCL and GL, respectively. (e) Sagittal section of the RMS and OB immunostained for the new neuron marker, DCX. The right panel shows a higher-magnification image of the boxed area at left. Whereas DCX-positive new neurons migrate tangentially in chains, new neurons that migrate radially do so as individuals. Scale bars: left, 500 μm; right, 200 μm. SVZ, subventricular zone; DG, dentate gyrus; OB, olfactory bulb; RMS, rostral migratory stream; GCL, granule cell layer; MCL, mitral cell layer; GL, glomerular layer; DCX, doublecortin.