Adult neurogenesis and functional plasticity in neuronal circuits

Lledo, Pierre−Marie; Alonso, Mariana; Grubb, Matthew S.

doi:10.1038/nrn1867

Cited by 1,223 publications

(998 citation statements)

References 221 publications

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“…The generation of new neurons is the end product of a series of steps consisting of proliferation, survival, migration, differentiation, and establishment of functional connections with other neurons (Lledo et al, 2006). In animals killed 24 h after BrdU injection, the BrdUpositive cells in the dentate gyrus represents the number of newly generated cells (cell proliferation rate; Figure 3a).…”

Section: Chronic Stress Inhibits Neurogenesis In the Dentate Gyrus: Rmentioning

confidence: 99%

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

Czéh

Müller-Keuker

Ryguła

et al. 2006

Neuropsychopharmacol

316

221

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Profound neuroplastic changes have been demonstrated in various limbic structures after chronic stress exposure and antidepressant treatment in animal models of mood disorders. Here, we examined in rats the effect of chronic social stress and concomitant antidepressant treatment on cell proliferation in the medial prefrontal cortex (mPFC). We also examined possible hemispheric differences. Animals were subjected to 5 weeks of daily social defeat by an aggressive conspecific and received concomitant, daily, oral fluoxetine (10 mg/kg) during the last 4 weeks. Bromodeoxyuridine (BrdU) labeling and quantitative stereological techniques were used to evaluate the treatment effects on proliferation and survival of newborn cells in limbic structures such as the mPFC and the hippocampal dentate gyrus, in comparison with nonlimbic structures such as the primary motor cortex and the subventricular zone. Phenotypic analysis showed that neurogenesis dominated the dentate gyrus, whereas in the mPFC most newborn cells were glia, with smaller numbers of endothelial cells. Chronic stress significantly suppressed cytogenesis in the mPFC and neurogenesis in the dentate gyrus, but had minor effect in nonlimbic structures. Fluoxetine treatment counteracted the inhibitory effect of stress. Hemispheric comparison revealed that the rate of cytogenesis was significantly higher in the left mPFC of control animals, whereas stress inverted this asymmetry, yielding a significantly higher incidence of newborn cells in the right mPFC. Fluoxetine treatment abolished hemispheric asymmetry in both control and stressed animals. These pronounced changes in gliogenesis after chronic stress exposure may relate to the abnormalities of glial cell numbers reported in the frontolimbic areas of depressed patients.

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Section: Chronic Stress Inhibits Neurogenesis In the Dentate Gyrus: Rmentioning

confidence: 99%

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

Czéh

Müller-Keuker

Ryguła

et al. 2006

Neuropsychopharmacol

316

221

View full text Add to dashboard Cite

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“…This is because repetitive division of stem and progenitor cells results in a continuous dilution of damaged macromolecules and organelles (here referred to as biological 'garbage' or 'waste'), while differentiated cells are frequently replaced and therefore do not accumulate any considerable amount of such 'garbage' [4,5]. Long-lived postmitotic cells, in contrast, are only rarely reinstated from stem cells [6,7], a fact that apparently determines their profound alterations by age ( Figure 1). …”

Section: Introductionmentioning

confidence: 99%

Autophagy, organelles and ageing

Terman

Gustafsson

Brunk

2007

The Journal of Pathology

263

210

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As a result of insufficient digestion of oxidatively damaged macromolecules and organelles by autophagy and other degradative systems, long-lived postmitotic cells, such as cardiac myocytes, neurons and retinal pigment epithelial cells, progressively accumulate biological 'garbage' ('waste' materials). The latter include lipofuscin (a non-degradable intralysosomal polymeric substance), defective mitochondria and other organelles, and aberrant proteins, often forming aggregates (aggresomes). An interaction between senescent lipofuscin-loaded lysosomes and mitochondria seems to play a pivotal role in the progress of cellular ageing. Lipofuscin deposition hampers autophagic mitochondrial turnover, promoting the accumulation of senescent mitochondria, which are deficient in ATP production but produce increased amounts of reactive oxygen species. Increased oxidative stress, in turn, further enhances damage to both mitochondria and lysosomes, thus diminishing adaptability, triggering mitochondrial and lysosomal pro-apoptotic pathways, and culminating in cell death.

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“…Only recently has it been recognized that adult neurogenesis replicates the complex process of neuronal development to generate functionally integrated new neurons ( Fig. 1) [15][16][17]. A role for these postnatally generated cells in learning was first suggested by Altman and Das in the 1960s [7-9,18].…”

mentioning

confidence: 99%

Adult Neurogenesis and Hippocampal Memory Function: New Cells, More Plasticity, New Memories?

Kitabatake

Sailor

Ming

et al. 2007

Neurosurgery Clinics of North America

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Memory consists of several separate entities that depend on various brain systems [1]. Clinical and behavioral evidence suggests that the hippocampus and the surrounding anatomically associated regions serve a critical role in learning and memory [2]. In the 1960s, the outlines of the essential neural substrates of memory were gradually elucidated based on analyzing the effects of therapeutic surgical lesions of the bilateral medial temporal lobes to suppress uncontrollable epilepsy in a patient [3]. Although the operation was effective in controlling the patient's epilepsy, one unexpected consequence was that he became profoundly amnesic while retaining his intelligence and perceptual and motor functions. Similar cases were also seen in other patients with damage to the hippocampal formation and surrounding medial temporal lobe structures [4]. These individuals had severe amnesia for episodic events, although other forms of learning and memory-semantic, perceptual, procedural, and simple forms of conditioning-were spared. It is now believed that the hippocampal formation has a central role in declarative memory, the ability to recollect everyday facts and events consciously [5]. The unique anatomy, electrophysiologic characteristics, and key roles in memory formation have made the hippocampus an attractive target of research for neuroscientists.For decades, it was believed that neurogenesis only occurred during embryonic stages in the mammalian central nervous system (CNS), making the brain one of the few mammalian organs incapable of replenishing its functional cell population throughout life [6]. In the 1960s, seminal studies by Altman and Das [7][8][9] provided the first evidence that new neurons were generated in the postnatal mammalian brain. In 1992, Reynolds and Weiss [10] isolated multipotent neural stem/progenitor cells (NSCs) from the adult rodent brain and characterized them in vitro. Studies in the 1990s confirmed that, contrary to long-held dogma, NSCs reside in the adult CNS and active neurogenesis occurs in discrete regions of the adult brain across various mammalian species, including mice, rats, monkeys, and humans [11][12][13][14]. Only recently has it been recognized that adult neurogenesis replicates the complex process of neuronal development to generate functionally integrated new neurons ( Fig. 1) [15][16][17]. A role for these postnatally generated cells in learning was first suggested by Altman and Das in the 1960s [7-9,18]. Later, Nottebohm [19] directly tested the role of * Corresponding author: shongju1@jhmi.edu (H. Song). HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript adult-generated neurons in song learning in birds. Subsequent work in rodents has led to the idea that adult neurogenesis is important for learning and memory of spatial information.The discovery of adult neurogenesis has generated significant interest, especially in regard to the hippocampus, not only for neuroscientists but for physicians who are engaged in treating various ...

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Adult neurogenesis and functional plasticity in neuronal circuits

Cited by 1,223 publications

References 221 publications

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

Autophagy, organelles and ageing

Adult Neurogenesis and Hippocampal Memory Function: New Cells, More Plasticity, New Memories?

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