Age-related decrease of striatal neurogenesis is associated with apoptosis of neural precursors and newborn neurons in rat brain after ischemia

Abstract

In this research, we investigated striatal neurogenesis in 3-, 6-, 12-, and 18-month-old rats after cerebral ischemic injury. All rats were subjected to a 20-min middle cerebral artery occlusion (MCAO), given 5′-bromodeoxyuridine (BrdU, 30 mg/kg, i.p.) once daily during days 4–7 and sacrificed 2 weeks after MCAO. Neurogenesis was assessed with double immunohistochemical/immunofluorescence labeling of BrdU and doublecortin (DCX), microtubule-associated protein 2 (MAP-2), or 67-kDa glutamic acid decarboxylase (GAD 67). In 6-, 12-, and 18-month-old rats, the numbers of nestin +, BrdU +–DCX + (a marker of newborn neuronal progenitors/immature neuron), BrdU +–MAP-2 + (a marker of newborn mature neuron), and BrdU +–GAD 67 + (a marker of newborn GABAergic neuron) cells decreased dramatically in the ipsilateral striatum to MCAO compared with that in 3-month-old rats. The results indicated that stroke-induced striatal neurogenesis still existed in aging rats. However, the capacity of neurogenesis in older rats was considerably lower than that in young adults. Meanwhile, the apoptosis of neural precursors and immature neurons, indicated by double labeling of active caspase-3 and nestin/DCX/Tuj-1(β-tubulin III)/CRMP-4 (collapsin response-mediated protein-4), increased noticeably in the ipsilateral striatum of older rats. Taken together, the results suggested that aging-related attenuation of ischemia-induced striatal neurogenesis might be related to decrease of neural precursors and increase of apoptosis of newborn neurons.