Interactions of estrogens and insulin-like growth factor-I in the brain: implications for neuroprotection

Interactions of estrogens and insulin-like growth factor-I in the brain: implications for... Data from epidemiological studies suggest that the decline in estrogen following menopause could increase the risk of neurodegenerative diseases. Furthermore, experimental studies on different animal models have shown that estrogen is neuroprotective. The mechanisms involved in the neuroprotective effects of estrogen are still unclear. Anti-oxidant effects, activation of different membrane-associated intracellular signaling pathways, and activation of classical nuclear estrogen receptors (ERs) could contribute to neuroprotection. Interactions with neurotrophins and other growth factors may also be important for the neuroprotective effects of estradiol. In this review we focus on the interaction between insulin-like growth factor-I (IGF-I) and estrogen signaling in the brain and on the implications of this interaction for neuroprotection. During the development of the nervous system, IGF-I promotes the differentiation and survival of specific neuronal populations. In the adult brain, IGF-I is a neuromodulator, regulates synaptic plasticity, is involved in the response of neural tissue to injury and protects neurons against different neurodegenerative stimuli. As an endocrine signal, IGF-I represents a link between the growth and reproductive axes and the interaction between estradiol and IGF-I is of particular physiological relevance for the regulation of growth, sexual maturation and adult neuroendocrine function. There are several potential points of convergence between estradiol and IGF-I receptor (IGF-IR) signaling in the brain. Estrogen activates the mitogen-activated protein kinase (MAPK) pathway and has a synergistic effect with IGF-I on the activation of Akt, a kinase downstream of phosphoinositol-3 kinase. In addition, IGF-IR is necessary for the estradiol induced expression of the anti-apoptotic molecule Bcl-2 in hypothalamic neurons. The interaction of ERs and IGF-IR in the brain may depend on interactions between neural cells expressing ERs with neural cells expressing IGF-IR, or on direct interactions of the signaling pathways of α and β ERs and IGF-IR in the same cell, since most neurons expressing IGF-IR also express at least one of the ER subtypes. In addition, studies on adult ovariectomized rats given intracerebroventricular (i.c.v.) infusions with antagonists for ERs or IGF-IR or with IGF-I have shown that there is a cross-regulation of the expression of ERs and IGF-IR in the brain. The interaction of estradiol and IGF-I and their receptors may be involved in different neural events. In the developing brain, ERs and IGF-IR are interdependent in the promotion of neuronal differentiation. In the adult, ERs and IGF-IR interact in the induction of synaptic plasticity. Furthermore, both in vitro and in vivo studies have shown that there is an interaction between ERs and IGF-IR in the promotion of neuronal survival and in the response of neural tissue to injury, suggesting that a parallel activation or co-activation of ERs and IGF-IR mediates neuroprotection. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Reviews Elsevier

Interactions of estrogens and insulin-like growth factor-I in the brain: implications for neuroprotection

Loading next page...
 
/lp/elsevier/interactions-of-estrogens-and-insulin-like-growth-factor-i-in-the-GsGsyDiJkw
Publisher
Elsevier
Copyright
Copyright © 2001 Elsevier Science B.V.
ISSN
0165-0173
D.O.I.
10.1016/S0165-0173(01)00137-0
Publisher site
See Article on Publisher Site

Abstract

Data from epidemiological studies suggest that the decline in estrogen following menopause could increase the risk of neurodegenerative diseases. Furthermore, experimental studies on different animal models have shown that estrogen is neuroprotective. The mechanisms involved in the neuroprotective effects of estrogen are still unclear. Anti-oxidant effects, activation of different membrane-associated intracellular signaling pathways, and activation of classical nuclear estrogen receptors (ERs) could contribute to neuroprotection. Interactions with neurotrophins and other growth factors may also be important for the neuroprotective effects of estradiol. In this review we focus on the interaction between insulin-like growth factor-I (IGF-I) and estrogen signaling in the brain and on the implications of this interaction for neuroprotection. During the development of the nervous system, IGF-I promotes the differentiation and survival of specific neuronal populations. In the adult brain, IGF-I is a neuromodulator, regulates synaptic plasticity, is involved in the response of neural tissue to injury and protects neurons against different neurodegenerative stimuli. As an endocrine signal, IGF-I represents a link between the growth and reproductive axes and the interaction between estradiol and IGF-I is of particular physiological relevance for the regulation of growth, sexual maturation and adult neuroendocrine function. There are several potential points of convergence between estradiol and IGF-I receptor (IGF-IR) signaling in the brain. Estrogen activates the mitogen-activated protein kinase (MAPK) pathway and has a synergistic effect with IGF-I on the activation of Akt, a kinase downstream of phosphoinositol-3 kinase. In addition, IGF-IR is necessary for the estradiol induced expression of the anti-apoptotic molecule Bcl-2 in hypothalamic neurons. The interaction of ERs and IGF-IR in the brain may depend on interactions between neural cells expressing ERs with neural cells expressing IGF-IR, or on direct interactions of the signaling pathways of α and β ERs and IGF-IR in the same cell, since most neurons expressing IGF-IR also express at least one of the ER subtypes. In addition, studies on adult ovariectomized rats given intracerebroventricular (i.c.v.) infusions with antagonists for ERs or IGF-IR or with IGF-I have shown that there is a cross-regulation of the expression of ERs and IGF-IR in the brain. The interaction of estradiol and IGF-I and their receptors may be involved in different neural events. In the developing brain, ERs and IGF-IR are interdependent in the promotion of neuronal differentiation. In the adult, ERs and IGF-IR interact in the induction of synaptic plasticity. Furthermore, both in vitro and in vivo studies have shown that there is an interaction between ERs and IGF-IR in the promotion of neuronal survival and in the response of neural tissue to injury, suggesting that a parallel activation or co-activation of ERs and IGF-IR mediates neuroprotection.

Journal

Brain Research ReviewsElsevier

Published: Nov 1, 2001

References

  • SK-ER3 neuroblastoma cells as a model for the study of estrogen influence on neural cells
    Agrati, P.; Garnier, M.; Patrone, C.; Pollio, G.; Santagati, S.; Vegeto, E.; Maggi, A.
  • Nongenomic effects of oestrogen: embryonic mouse midbrain neurones respond with a rapid release of calcium from intracellular stores
    Beyer, C.; Raab, H.
  • Differential effect of oestradiol and astroglia-conditioned media on the growth of hypothalamic neurons from male and female rat brains
    Cambiasso, M.J.; Colombo, J.A.; Carrer, H.F.
  • Sex steroids and the brain: lessons from animal studies
    Chowen, J.A.; Azcoitia, I.; Cardona-Gomez, G.P.; Garcia-Segura, L.M.
  • Estrogen facilitates induction of long term potentiation in the hippocampus of awake rats
    Cordoba Montoya, D.A.; Carrer, H.F.
  • Neuroprotective actions of peripherally administered insulin-like growth factor I in the injured olivo-cerebellar pathway
    Fernandez, A.M.; Gonzalez de la Vega, A.; Planas, B.; Torres-Aleman, I.
  • Phasic synaptic remodeling in the rat arcuate nucleus during the estrous cycle depends on insulin like growth factor-I receptor activation
    Fernandez-Galaz, M.C.; Naftolin, F.; Garcia-Segura, L.M.
  • Role of astroglia and insulin-like growth factor-I in gonadal hormone dependent synaptic plasticity
    Fernandez-Galaz, M.C.; Morschl, E.; Chowen, J.A.; Torres-Aleman, I.; Naftolin, F.; Garcia-Segura, L.M.
  • Treatment with estrogen and progesterone affects relative levels of brain-derived neurotrophic factor mRNA and protein in different regions of the adult rat brain
    Gibbs, R.B.
  • N-terminal tripeptide of IGF-1 (GPE) prevents the loss of TH positive neurons after 6-OHDA induced nigral lesion in rats
    Guan, J.; Krishnamurthi, R.; Waldvogel, H.J.; Faull, R.L.; Clark, R.; Gluckman, P.
  • Insulin-like growth factors and their binding proteins: biological actions
    Jones, J.I.; Clemmons, D.R.
  • Estrogen: mechanisms for a rapid action in CA1 hippocampal neurons
    Moss, R.L.; Gu, Q.
  • Synaptic remodeling in the rat arcuate nucleus during the estrous cycle
    Olmos, G.; Naftolin, F.; Perez, J.; Tranque, P.A.; Garcia-Segura, L.M.
  • Estrogen replacement therapy and stroke
    Paganini-Hill, A.
  • Rapid upregulation of aromatase mRNA and protein following neural injury in the zebra finch ( Taeniopygia guttata )
    Peterson, R.S.; Saldanha, C.J.; Schlinger, B.A.
  • Activated phosphatidylinositol 3-kinase and Akt kinase promote survival of superior cervical neurons
    Philpott, K.L.; McCarthy, M.J.; Klippel, A.; Rubin, L.L.
  • Estradiol modulates insulin-like growth factor I receptors and binding proteins in neurons from the hypothalamus
    Pons, S.; Torres-Aleman, I.
  • Estrogen desensitizes 5-HT(1A) receptors and reduces levels of G(z), G(i1) and G(i3) proteins in the hypothalamus
    Raap, D.K.; DonCarlos, L.; Garcia, F.; Muma, N.A.; Wolf, W.A.; Battaglia, G.; van de Kar, L.D.
  • Neuroprotective effects of chronic estradiol benzoate treatment on hippocampal cell loss induced by status epilepticus in the female rat
    Reibel, S.; André, V.; Chassagnon, S.; André, G.; Marescaux, C.; Nehlig, A.; Depaulis, A.
  • Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury
    Saatman, K.E.; Contreras, P.C.; Smith, D.H.; Raghupathi, P.; McDermott, K.L.; Fernandez, S.C.; L Sanderson, K.; Voddi, M.; McIntosh, T.K.
  • The insulin-like growth factor I system in the rat cerebellum: developmental regulation and role in neuronal survival and differentiation
    Torres-Aleman, I.; Pons, S.; Arevalo, M.A.
  • Neuroprotective effects of estrogens on hippocampal cells in adult female rats after status epilepticus
    Veliskova, J.; Velisek, L.; Galanopoulou, A.S.; Sperber, E.F.
  • Systemic administration of insulin-like growth factor decreases motor neuron cell death and promotes muscle reinnervation
    Vergani, L.; Di Giulio, A.M.; Losa, M.; Rossoni, G.; Muller, E.E.; Gorio, A.
  • Reduction of ischemic brain injury by topical application of insulin-like growth factor-I after transient middle cerebral artery occlusion in rats
    Wang, J.M.; Hayashi, T.; Zhang, W.R.; Sakai, K.; Shiro, Y.; Abe, K.
  • Estradiol protects against injury-induced cell death in cortical explant cultures: a role for estrogen receptors
    Wilson, M.E.; Dubal, D.B.; Wise, P.M.
  • Insulin-like growth factors and ovarian physiology
    Yoshimura, Y.
  • Effects of gender and estradiol treatment on focal brain ischemia
    Zhang, Y.Q.; Shi, J.; Rajakumar, G.; Day, A.L.; Simpkins, J.W.
  • Oestrogen-induced changes in the synaptology of the monkey ( Cercopithecus aethiops ) arcuate nucleus during gonadotropin feedback
    Zsarnovszky, A.; Horvath, T.L.; Garcia-Segura, L.M.; Horvath, B.; Naftolin, F.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off