Age-dependent decline in hippocampal neurogenesis is not altered by chronic treatment with fluoxetine

Cowen, David L.; Takase, Luiz Fernando; Fornal, Casimir A.; Jacobs, Barry L.

doi:10.1016/j.brainres.2008.06.059

Cited by 61 publications

(55 citation statements)

References 27 publications

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“…However, after lack of success in producing the expected result, communications between our group and researchers from other laboratories revealed that many had experienced similar difficulties in reproducing this effect. Most of these negative results have not been published, with notable exceptions involving fluoxetine in two studies and citalopram in a third (Jaako-Movits et al, 2006;Cowen et al, 2008;David et al, 2009; it is important to note that each of these studies also used behaviorally active antidepressant doses).…”

Section: Discussionmentioning

confidence: 99%

“…NPC proliferation rate and immature neuron survival rate have been up-regulated by 14 or more days of treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine, but not by shorter regimens (Malberg et al, 2000;Kodama et al, 2004;Huang and Herbert, 2006;Marcussen et al, 2008), although this effect has not been observed universally (Cowen et al, 2008;David et al, 2009). Experiments involving the SSRI citalopram/escitalopram have been less successful, with negative results outnumbering positive ones, with regard to both proliferation and survival (Jaako-Movits et al, 2006;Jayatissa et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Lithium, but Not Fluoxetine or the Corticotropin-Releasing Factor Receptor 1 Receptor Antagonist R121919, Increases Cell Proliferation in the Adult Dentate Gyrus

Hanson

Nemeroff

Owens

2011

J Pharmacol Exp Ther

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Several antidepressant drugs have previously been reported to increase neurogenesis in the dentate gyrus of the hippocampus in laboratory animals. We found no effect of the selective serotonin reuptake inhibitor fluoxetine or the corticotropin-releasing factor receptor 1 antagonist R121919 [3-on the rate of cell proliferation or hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression in either adult or adolescent rats after long-term administration. In adults, the mood stabilizer lithium was found to significantly increase cell proliferation; the atypical antipsychotic paliperidone did not affect proliferation, either alone or when combined with lithium. Fourteen-day survival of neuronally fated cells showed a significant interaction effect of lithium and paliperidone but no effect of either drug alone. BDNF mRNA expression was significantly decreased by lithium in the CA1/2 cell fields and increased by paliperidone in the CA1/2, CA3, and dentate gyrus. These results raise questions concerning the hypothesis that all antidepressants increase neurogenesis under nonstressed conditions. They also confirm and extend previous reports of lithium-induced increases in cell proliferation but not survival.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lithium, but Not Fluoxetine or the Corticotropin-Releasing Factor Receptor 1 Receptor Antagonist R121919, Increases Cell Proliferation in the Adult Dentate Gyrus

Hanson

Nemeroff

Owens

2011

J Pharmacol Exp Ther

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“…However, whether their integration and diVerentiation into mature neurons is of functional signiWcance is still a matter of debate [17,22,48,64]. In rodents, a decrease of the magnitude of hippocampal neurogenesis with increasing age is well known [9,19,25,42]. However, recent data suggest that hippocampal neurogenesis in rats appears to remain relatively unaltered in adulthood [18].…”

Section: Introductionmentioning

confidence: 91%

“…Since then, diVerent new methods have veriWed the proliferation of neural progenitor cells and their diVerentiation into mature neurons within the granule cell layer of the hippocampal dentate gyrus in both adult mammalian [1,9,17,19,22,25,38,48,53,64] and human brains [2,3,6,12,21,31,37,52,56].…”

Section: Introductionmentioning

confidence: 99%

Increased neurogenesis after hypoxic-ischemic encephalopathy in humans is age related

et al. 2009

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The leading cause of morbidity and mortality after successful resuscitation is hypoxic-ischemic encephalopathy (HIE), which results in neuronal loss within the neocortex and the hippocampal formation. This study focuses on the impact of HIE on adult neurogenesis in the human hippocampal dentate gyrus as a potential intrinsic regenerative mechanism in response to neuronal damage. Brain sections of 22 autopsy cases with HIE and of 19 agematched controls without neuropathological abnormalities were investigated by means of immunohistochemistry. The densities of immature granule cells during axon guidance and outgrowth (assessed by TUC-4 immunohistochemistry) and of young calretinin-expressing postmitotic neurons were increased in the granule cell layer of cases who had suVered from HIE (P = 0.0002 and P = 0.0001, respectively). Similarly, the density of apoptotic granule cells, as detected by in situ tailing and morphological criteria, was increased in HIE (P = 0.014). In cases with HIE, the increase in the density of TUC-4-labeled cells inversely correlated with age (P = 0.027). In contrast, neither the density of proliferating nor that of apoptotic cells was substantially inXuenced by age within the control group. Taken together, both an increase in adult neurogenesis and in neuronal apoptosis was observed in the human dentate gyrus in response to HIE. The data suggest a decrease of adult neurogenesis in older-aged cases. Whether neurogenesis can contribute to recovery after HIE remains to be determined. The stimulation of adult neurogenesis may be less eYcient in older victims of HIE.

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“…41 In the later study however, only proliferation was assessed under ongoing chronic fluoxetine treatment.…”

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confidence: 99%

Ageing abolishes the effects of fluoxetine on neurogenesis

et al. 2009

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Depression constitutes a widespread condition observed in elderly patients. Recently, it was found that several drugs employed in therapies against depression stimulate hippocampal neurogenesis in young rodents and nonhuman primates. As the rate of neurogenesis is dramatically reduced during ageing, we examined the influences of ageing on neurogenic actions of antidepressants. We tested the impact of fluoxetine, a broadly used antidepressant, on hippocampal neurogenesis in mice of three different age groups (100, 200 and over 400 days of age). Proliferation and survival rate of newly generated cells, as well as the percentage of cells that acquired a neuronal phenotype were analyzed in the hippocampus of mice that received fluoxetine daily in a chronic manner. Surprisingly, the action of fluoxetine on neurogenesis was decreasing as a function of age and was only significant in young animals. Hence, fluoxetine increased survival and the frequency of neuronal marker expression in newly generated cells of the hippocampus in the young adult group (that is 100 days of age) only. No significant effects on neurogenesis could be detected in fluoxetine-treated adult and elderly mice (200 and over 400 days of age). The data indicate that the action of fluoxetine on neurogenesis is highly dependent on the age of the treated individual. Although the function of neurogenesis in the clinical manifestation of depression is currently a matter of speculation, this study clearly shows that the therapeutic effects of antidepressants in elderly patients are not mediated by neurogenesis modulation.

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Age-dependent decline in hippocampal neurogenesis is not altered by chronic treatment with fluoxetine

Cited by 61 publications

References 27 publications

Lithium, but Not Fluoxetine or the Corticotropin-Releasing Factor Receptor 1 Receptor Antagonist R121919, Increases Cell Proliferation in the Adult Dentate Gyrus

Lithium, but Not Fluoxetine or the Corticotropin-Releasing Factor Receptor 1 Receptor Antagonist R121919, Increases Cell Proliferation in the Adult Dentate Gyrus

Increased neurogenesis after hypoxic-ischemic encephalopathy in humans is age related

Ageing abolishes the effects of fluoxetine on neurogenesis

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