Antidepressants and Cdk inhibitors: Releasing the brake on neurogenesis?

Chesnokova, Vera; Pechnick, Robert N.

doi:10.4161/cc.6446

Cited by 13 publications

(11 citation statements)

References 98 publications

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“…Co-treatment with antidepressants and neurotoxins prevented or reversed neurotoxin-induced changes in cell cycle, except for pargyline and deprenyl. Such effects of antidepressants on cell cycle transition is consistent with the recent reports that chronic treatment with different classes of antidepressants down-regulated expression of cell cycle inhibitors (Pechnick et al 2008, Pechnick et al 2011, Epp et al 2013), indicating that cell-cycle regulation occurs downstream from the primary site of antidepressant action (Chesnokova & Pechnick 2008). G1- to S-phase transition is one of the most important steps in the cell cycle.…”

Section: Discussionsupporting

confidence: 91%

“…Since antidepressants including SSRIs and tricyclics, increase cellular proliferation in adult rodent hippocampus (Malberg et al 2000, Lagace et al 2007, Green & Galea 2008), while chronic stress and high glucocorticids reduce cell proferatioin levels (Gould et al 1997, Brummelte & Galea 2010), down-regulatory effects of antidepressants on CDK inhibitors of p21 have been interpreted as releasing proliferation restraint and increasing neurogenesis in the brain. Intriguingly, our observations and reports in the literature (Chesnokova & Pechnick 2008, Pechnick et al 2008, Pechnick et al 2011, Epp et al 2013) may provide evidence to correlate the cell cycle regulation, neurogenesis, antidepressant drugs, and depression.…”

Section: Discussionsupporting

confidence: 79%

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Effects of Antidepressants on DSP4/CPT-Induced DNA Damage Response in Neuroblastoma SH-SY5Y Cells

et al. 2015

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DNA damage is a form of cell stress and injury. Increased systemic DNA damage is related to the pathogenic development of neurodegenerative diseases. Depression occurs in a relatively high percentage of patients suffering from degenerative diseases, for whom antidepressants are often used to relieve depressive symptoms. However, few studies have attempted to elucidate why different groups of antidepressants have similar effects on relieving symptoms of depression. Previously, we demonstrated that neurotoxins N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4)- and camptothecin (CPT)-induced the DNA damage response in SH-SY5Y cells, and DSP4 caused cell cycle arrest which was predominately in the S-phase. The present study shows that CPT treatment also resulted in similar cell cycle arrest. Some classic antidepressants could reduce the DNA damage response induced by DSP4 or CPT in SH-SY5Y cells. Cell viability examination demonstrated that both DSP4 and CPT caused cell death, which was prevented by spontaneous administration of some tested antidepressants. Flow cytometric analysis demonstrated that a majority of the tested antidepressants protect cells from being arrested in S-phase. These results suggest that blocking the DNA damage response may be an important pharmacologic characteristic of antidepressants. Exploring the underlying mechanisms may allow for advances in the effort to improve therapeutic strategies for depression appearing in degenerative and psychiatric diseases.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 79%

Effects of Antidepressants on DSP4/CPT-Induced DNA Damage Response in Neuroblastoma SH-SY5Y Cells

et al. 2015

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“…This neurogenesis may be associated with maintenance or restoration of neurological function in animal models of CNS diseases, suggesting that neurogenesis is functionally important to recovery (Palmer et al, 2000; Ohab et al, 2006; Abdipranoto et al, 2008; Chesnokova and Pechnick, 2008; Liu et al, 2009a). Neurogenesis arises from brain progenitor cells, rather than from differentiated adult neurons.…”

Section: Agents That Interfere With Molecules and Pathways Of The “Exmentioning

confidence: 99%

Cell cycle inhibition without disruption of neurogenesis is a strategy for treatment of central nervous system diseases

Liu¹,

Ander²,

Sharp³

2010

Neurobiology of Disease

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Classically, the cell cycle is regarded as the central process leading to cellular proliferation. However, increasing evidence over the last decade supports the notion that neuronal cell cycle re-entry results in post-mitotic death. A mature neuron that re-enters the cell cycle can neither advance to a new G0 quiescent state nor revert to its earlier G0 state. This presents a critical dilemma to the neuron from which death may be an unavoidable, but necessary, outcome for adult neurons attempting to complete the cell cycle. In contrast, tumor cells that undergo aberrant cell cycle re-entry divide and can survive. Thus, cell cycle inhibition strategies are of interest in cancer treatment, but may also represent an important means of protecting neurons. In this review, we put forth the concept of the "expanded cell cycle" and summarize the cell cycle proteins, signal transduction events and mitogenic molecules that can drive a neuron into the cell cycle in various CNS diseases. We also discuss the pharmacological approaches that interfere with the mitogenic pathways and prevent mature neurons from attempting cell cycle re-entry, protecting them from cell death. Lastly, future attempts at blocking the cell cycle to rescue mature neurons from injury should be designed so as to not block normal neurogenesis.

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“…The generation of new neurons in the hippocampal niche of the adult brain, depends on the harmonization of several processes and cellular activities, which include proliferation, cell cycle exit, activation of survival/death pathways, migration through the GCL and differentiation/maturation of the newborn neurons [34]. These processes are regulated by both intrinsic and extrinsic factors that are ultimately responsible for the modulation of the neurogenic phenomenon.…”

Section: Introductionmentioning

confidence: 99%

“…Whereas during development, the cellular environment is highly specialized to support proliferation, in the adult hippocampus the environmental context includes a population of fully mature and functionally active neurons [7, 37], thus providing a different set of both intrinsic and extrinsic signals. In fact, in the adult mammalian brain, the vast majority of neuronal cells are in a quiescent differentiated state (G0 phase of the cell cycle), which is probably promoted by an increase in the expression of region-specific Cdk inhibitors [34, 41, 42]. Nonetheless, the expression of cell cycle proteins in the postnatal brain and their definite role in this neurogenic niche are still being unveiled [36].…”

Section: Introductionmentioning

confidence: 99%

Re-cycling Paradigms: Cell Cycle Regulation in Adult Hippocampal Neurogenesis and Implications for Depression

et al. 2013

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Since adult neurogenesis became a widely accepted phenomenon, much effort has been put in trying to understand the mechanisms involved in its regulation. In addition, the pathophysiology of several neuropsychiatric disorders, such as depression, has been associated with imbalances in adult hippocampal neurogenesis. These imbalances may ultimately reflect alterations at the cell cycle level, as a common mechanism through which intrinsic and extrinsic stimuli interact with the neurogenic niche properties. Thus, the comprehension of these regulatory mechanisms has become of major importance to disclose novel therapeutic targets. In this review, we first present a comprehensive view on the cell cycle components and mechanisms that were identified in the context of the homeostatic adult hippocampal neurogenic niche. Then, we focus on recent work regarding the cell cycle changes and signaling pathways that are responsible for the neurogenesis imbalances observed in neuropathological conditions, with a particular emphasis on depression.

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Antidepressants and Cdk inhibitors: Releasing the brake on neurogenesis?

Cited by 13 publications

References 98 publications

Effects of Antidepressants on DSP4/CPT-Induced DNA Damage Response in Neuroblastoma SH-SY5Y Cells

Effects of Antidepressants on DSP4/CPT-Induced DNA Damage Response in Neuroblastoma SH-SY5Y Cells

Cell cycle inhibition without disruption of neurogenesis is a strategy for treatment of central nervous system diseases

Re-cycling Paradigms: Cell Cycle Regulation in Adult Hippocampal Neurogenesis and Implications for Depression

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