Neurosteroids as modulators of neurogenesis and neuronal survival

Charalampopoulos, Ioannis; Remboutsika, Eumorphia; Margioris, Andrew N.; Gravanis, Achille

doi:10.1016/j.tem.2008.07.004

Cited by 177 publications

(118 citation statements)

References 70 publications

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“…In addition, estrogen protects against experimental ischemic stroke [16,19], chronic inflammatory diseases [20] and dopaminergic system dysfunction following the administration of a variety of neurotoxins [21,22], including kainic acid and 6-hydroxydopamine.…”

Section: Introductionmentioning

confidence: 99%

Effects of 17<i>β</i>-Estradiol on Cognitive Performance of Ovariectomized Female Rats Exposed to Space Radiation

Rabin¹,

Carrihill-Knoll²,

Long³

et al. 2013

JBBS

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On exploratory class missions to other planets astronauts will be exposed to types and doses of radiation that are not experienced in low earth orbit. While it is likely that the crew will consist of both male and female astronauts, there has been little research on the effects of exposure to space radiation on central nervous system function and cognitive performance in female subjects. Because estrogen can function as a neuroprotectant, the present experiments were designed to evaluate whether or not the presence or absence of estrogen at the time of irradiation would affect the susceptibility to the neurocognitive effects of exposure to 56 Fe particles in female rats. Capsules containing 17β-estradiol or vehicle were implanted in ovariectomized rats three days prior to exposure 56 Fe particles (50 -200 cGy, 1000 MeV/n). Cognitive performance was evaluated using novel object recognition memory to measure learning and memory and operant responding on an ascending fixed-ratio schedule to measure changes in motivation and in the responsiveness to environmental contingencies. The results indicated the estrogen does not function as a neuroprotectant to minimize the cognitive effects of exposure to 56 Fe particles. However, the presence/absence of estrogen at the time of irradiation could modulate the responsiveness of the subject to the disruptive effects of exposure to HZE particles on the performance of specific cognitive tasks.

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Section: Introductionmentioning

confidence: 99%

Effects of 17<i>β</i>-Estradiol on Cognitive Performance of Ovariectomized Female Rats Exposed to Space Radiation

Rabin¹,

Carrihill-Knoll²,

Long³

et al. 2013

JBBS

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“…In the nervous system, neurotransmission, receptor function, and the strength of synaptic transmission is modified by pregnenolone sulfate stimulation (Baulieu, 1998). Intracerebral infusion of pregnenolone sulfate was shown to influence cognitive processes, neuronal survival, and neurogenesis (Mayo et al, 2001;Charalampopoulos et al, 2008). In pancreatic ␤ cells and insulinoma cells, pregnenolone sulfate triggers a rapid Ca 2ϩ influx into the cells, leading to enhanced insulin secretion (Wagner et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Pregnenolone Sulfate Activates Basic Region Leucine Zipper Transcription Factors in Insulinoma Cells: Role of Voltage-Gated Ca²⁺Channels and Transient Receptor Potential Melastatin 3 Channels

Muller

Rößler²,

Thiel³

2011

Mol Pharmacol

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The neurosteroid pregnenolone sulfate activates a signaling cascade in insulinoma cells involving activation of extracellular signal-regulated protein kinase and enhanced expression of the transcription factor Egr-1. Here, we show that pregnenolone sulfate stimulation leads to a significant elevation of activator protein-1 (AP-1) activity in insulinoma cells. Expression of the basic region leucine zipper (bZIP) transcription factors c-Jun and c-Fos is up-regulated in insulinoma cells and pancreatic ␤-cells in primary culture after pregnenolone sulfate stimulation. Up-regulation of a chromatin-embedded c-Jun promoter/ luciferase reporter gene transcription in pregnenolone sulfatestimulated insulinoma cells was impaired when the AP-1 binding sites were mutated, indicating that these motifs function as pregnenolone sulfate response elements. In addition, phosphorylation of cAMP response element (CRE)-binding protein is induced and transcription of a CRE-controlled reporter gene is stimulated after pregnenolone sulfate treatment, indicating that the CRE functions as a pregnenolone sulfate response element as well. Pharmacological and genetic experiments revealed that both L-type Ca 2ϩ channels and transient receptor potential melastatin 3 (TRPM3) channels are essential for connecting pregnenolone sulfate stimulation with enhanced AP-1 activity and bZIP-mediated transcription in insulinoma cells. In contrast, pregnenolone sulfate stimulation did not enhance AP-1 activity or c-Jun and c-Fos expression in pituitary corticotrophs that express functional L-type Ca 2ϩ channels but only trace amounts of TRPM3. We conclude that expression of L-type Ca 2ϩ channels is not sufficient to activate bZIP-mediated gene transcription by pregnenolone sulfate. Rather, additional expression of TRPM3 or depolarization of the cells is required to connect pregnenolone sulfate stimulation with enhanced gene transcription.

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“…The unique place of neuroactive steroids in this setting is given further support by a growing body of evidence showing that these agents are important for both improving the survival of neurons and increasing the number of newly formed neurons (Charalampopoulos et al, 2008). Fig.…”

Section: Discussionmentioning

confidence: 94%

Targeting the Modulation of Neural Circuitry for the Treatment of Anxiety Disorders

Farb

Ratner

2014

Pharmacol Rev

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Neurosteroids as modulators of neurogenesis and neuronal survival

Cited by 177 publications

References 70 publications

Effects of 17<i>β</i>-Estradiol on Cognitive Performance of Ovariectomized Female Rats Exposed to Space Radiation

Effects of 17<i>β</i>-Estradiol on Cognitive Performance of Ovariectomized Female Rats Exposed to Space Radiation

Pregnenolone Sulfate Activates Basic Region Leucine Zipper Transcription Factors in Insulinoma Cells: Role of Voltage-Gated Ca²⁺Channels and Transient Receptor Potential Melastatin 3 Channels

Targeting the Modulation of Neural Circuitry for the Treatment of Anxiety Disorders

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Neurosteroids as modulators of neurogenesis and neuronal survival

Cited by 177 publications

References 70 publications

Effects of 17&lt;i&gt;β&lt;/i&gt;-Estradiol on Cognitive Performance of Ovariectomized Female Rats Exposed to Space Radiation

Effects of 17&lt;i&gt;β&lt;/i&gt;-Estradiol on Cognitive Performance of Ovariectomized Female Rats Exposed to Space Radiation

Pregnenolone Sulfate Activates Basic Region Leucine Zipper Transcription Factors in Insulinoma Cells: Role of Voltage-Gated Ca2+Channels and Transient Receptor Potential Melastatin 3 Channels

Targeting the Modulation of Neural Circuitry for the Treatment of Anxiety Disorders

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Effects of 17<i>β</i>-Estradiol on Cognitive Performance of Ovariectomized Female Rats Exposed to Space Radiation

Effects of 17<i>β</i>-Estradiol on Cognitive Performance of Ovariectomized Female Rats Exposed to Space Radiation

Pregnenolone Sulfate Activates Basic Region Leucine Zipper Transcription Factors in Insulinoma Cells: Role of Voltage-Gated Ca²⁺Channels and Transient Receptor Potential Melastatin 3 Channels