Functional neurogenesis in the adult hippocampus

Praag, Henriette van; Schinder, Alejandro F.; Christie, Brian R.; Toni, Nicolas; Palmer, Theo D.; Gage, Fred H.

doi:10.1038/4151030a

Cited by 2,540 publications

(1,892 citation statements)

References 31 publications

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“…These neuroblasts, upon completing migration, are capable of maturing into fully differentiated neurons, integrating into local synaptic circuits and may be important in adult cognitive processing [8][9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

et al. 2006

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The ability of the mature mammalian nervous system to continually produce neuronal precursors is of considerable importance, as manipulation of this process might one day permit the replacement of cells lost as a result of injury or disease. In mammals, the anterior subventricular zone (SVZa) region is one of the primary sites of adult neurogenesis. Here we show that Doublecortin (DCX), a widely used marker for newly generated neurons, when deleted in mouse results in a severe morphological defect in the rostral migratory stream and delayed neuronal migration that is independent of direction or responsiveness to Slit chemorepulsion. DCX is required for nuclear translocation and maintenance of bipolar morphology during migration of these cells. Our data identifies a critical function for DCX in the movement of newly generated neurons in the adult brain.In the rodent and primate brain, the anterior region of the lateral ventricle and the hippocampus are the primary sites of adult neurogenesis [1][2][3][4][5][6][7] . These neuroblasts, upon completing migration, are capable of maturing into fully differentiated neurons, integrating into local synaptic circuits and may be important in adult cognitive processing [8][9][10][11] .The mechanisms controlling the targeted translocation of large numbers of cells to the olfactory bulb (OB) over a considerable distance (>5 mm in the adult mouse) are an issue of intense investigation. These neurons translocate using a process known as chain migration, whereby the cells use each other as the migratory substrate 12 . These newly generated neurons are derived from SVZa glial fibrillary acidic protein (GFAP)-positive astrocytes 13,14 , which also ensheath them as they move through extensive interconnected networks along the lining of the lateral ventricle in the rostral forebrain and the rostral migratory stream (RMS) 15 . There, they are under the control of extracellular migration guidance cues, including the secreted ligands Slit and Reelin [16][17][18][19] , the receptors ErbB4 and Deleted in Colorectal Carcinoma (DCC) 20,21 , as well as integrins and neural cell adhesion molecule [21][22][23] . Upon reaching the bulb, the neurons turn and migrate in a radial direction 24 , integrating into either the granule cell layer or the periglomerular network 25 . 3The X-linked gene doublecortin (DCX) is mutated in some patients with the severe neuronal migration defect called classical lissencephaly or double cortex syndrome 26,27 . This migration defect is likely to be cell autonomous, because in females with a heterozygous mutation, approximately half of the neurons are misplaced within the cerebral cortex as would be expected from random X-chromosome inactivation. As a result, males display a four-layered agyric cortex and females display a subcortical band of heterotopic neurons. It was surprising, therefore, that the Dcx knockout mice displayed no appreciable defect in cortical neuronal lamination or positioning 28 . One possible explanation for these species differences ...

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Section: Introductionmentioning

confidence: 99%

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

et al. 2006

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“…The dentate gyrus of the hippocampus is one of the few adult brain regions where proliferating cells differentiate into young neurons [1,2], which integrate anatomically and physiologically into the hippocampal neuronal network [3][4][5][6]. Changes in the extent of adult hippocampal neurogenesis are associated with changes in the performance of animals in hippocampus-dependent behavioral tasks [7][8][9][10][11], and a recent study of conditional TLX knockout mice, a gene expressed by adult neural stem cells, suggest a causal link between the performance in specific aspects of behavioral tasks and neurogenesis [12].…”

Section: Introductionmentioning

confidence: 99%

A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice

Klaus

Hauser

Slomianka

et al. 2009

Behavioural Brain Research

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A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice Klaus, F; Hauser, T; Slomianka, L; Amrein, I; Lipp, H P Klaus, F; Hauser, T; Slomianka, L; Amrein, I; Lipp, H P (2009). A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice. A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice Abstract Exercise is one of the best-known stimulators of adult hippocampal neurogenesis, but it is not known if voluntary changes in the intensity of exercise are accompanied by changes in neurogenesis. In this study we investigated whether a reward influences the performance in a running wheel and the rate of cell proliferation, neuronal differentiation and cell death in C57BL/6 mice. Mice had free access to a running wheel during the first week of the experiment. In the second week, animals were rewarded for their performance and compared to normal voluntary running and control mice. A reward significantly increased the performance by 78% when compared to the non-rewarded performance of the first week.The performance of the non-rewarded runners remained relatively constant. Fourteen days of exercise significantly increased cell proliferation by 27% and the number of doublecortin immunoreactive cells by 46%. A reward and the associated increase of performance did not modulate proliferation, cell death or the number of cells entering the neuronal lineage. We suggest that, in C57BL/6 mice, either exercise increases adult hippocampal neurogenesis to a ceiling value, which is reached by a performance at or below the level achieved by voluntary wheel running, or that a possible positive effect of increased running-wheel activity is balanced by stress resulting from rewarded running, which is no longer performed on a strictly voluntary basis. We suggest that, in C57BL/6 mice, either exercise increases adult hippocampal neurogenesis to a ceiling value, which is reached by a performance at or below the level achieved by voluntary wheel running, or that a possible positive effect of increased is balanced by stress resulting from rewarded running, which is no longer performed on a strictly voluntary basis.

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“…Most importantly, newly born granular neurons are incorporated into the neural circuitry and mature into functional neurons. 12 The specific function of these neurons is not yet clear, 13 but some hippocampus-dependent learning and memory tasks have been related to an increased neurogenesis, 14,15 suggesting that they might contribute to cognitive processes.…”

Section: Introductionmentioning

confidence: 99%

Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior

et al. 2006

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Hormonal imbalances are involved in many of the age-related pathologies, as neurodegenerative and psychiatric diseases. Specifically, thyroid state alterations in the adult are related to psychological changes and mood disorders as depression. The dentate gyrus of the hippocampal formation undergoes neurogenesis in adult mammals including humans. Recent evidence suggests that depressive disorders and their treatment are tightly related to the number of newly born neurons in the dentate gyrus. We have studied the effect of thyroid hormones (TH) on hippocampal neurogenesis in adult rats in vivo. A short period of adultonset hypothyroidism impaired normal neurogenesis in the subgranular zone of the dentate gyrus with a 30% reduction in the number of proliferating cells. Hypothyroidism also reduced the number of newborn neuroblasts and immature neurons (doublecortin (DCX) immunopositive cells) which had a severely hypoplastic dendritic arborization. To correlate these changes with hippocampal function, we subjected the rats to the forced swimming and novel object recognition tests. Hypothyroid rats showed normal memory in object recognition, but displayed abnormal behavior in the forced swimming test, indicating a depressive-like disorder. Chronic treatment of hypothyroid rats with TH not only normalized the abnormal behavior but also restored the number of proliferative and DCX-positive cells, and induced growth of their dendritic trees. Therefore, hypothyroidism induced a reversible depressive-like disorder, which correlated to changes in neurogenesis. Our results indicate that TH are essential for adult hippocampal neurogenesis and suggest that mood disorders related to adult-onset hypothyroidism in humans could be due, in part, to impaired neurogenesis.

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Functional neurogenesis in the adult hippocampus

Cited by 2,540 publications

References 31 publications

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain

A reward increases running-wheel performance without changing cell proliferation, neuronal differentiation or cell death in the dentate gyrus of C57BL/6 mice

Modulation of adult hippocampal neurogenesis by thyroid hormones: implications in depressive-like behavior

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