Review
Influence of different estrogens on neuroplasticity and cognition in the hippocampus

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Abstract

Background

Estrogens modulate the morphology and function of the hippocampus. Recent studies have focused on the effects of different types of estrogens on neuroplasticity in the hippocampus and cognition. There are three main forms of estrogens found in mammals: estradiol, estrone, and estriol. The vast majority of studies have used estradiol to investigate the effects of estrogens on the brain.

Scope of review

This review focuses on the effects of different estrogens on adult hippocampal neurogenesis, synaptic plasticity in the hippocampus, and cognition in female rats.

Major conclusions

Different forms of estrogens modulate neuroplasticity and cognition in complex and intriguing ways. Specifically, estrogens upregulate adult hippocampal neurogenesis (via cell proliferation) and synaptic protein levels in the hippocampus in a time- and dose-dependent manner. Low levels of estradiol facilitate spatial working memory and contextual fear conditioning while high levels of estradiol impair spatial working, spatial reference memory and contextual fear conditioning. In addition, estrone impairs contextual fear conditioning.

General significance

Advances in our knowledge of how estrogens exert their effects on the brain may ultimately lead to refinements in targeted therapies for cognitive impairments at all stages of life. However caution should be taken in interpreting current research and in conducting future studies as estrogens likely work differently in males than in females.

Section snippets

What is adult neurogenesis and how to study it?

The birth and maturation of new neurons in adulthood, adult neurogenesis, has been found in nearly all mammalian species studied to date, including humans [6], [7], [8], [9], [10], [11], [12], [13]. Adult neurogenesis has been confirmed in at least two main areas: the subventricular zone (new cells from this area migrate to the olfactory bulbs along the rostral migratory stream) and the dentate gyrus of the hippocampus (see Fig. 1). The subgranular zone of the dentate gyrus contains progenitor

Influence of estrogens on other forms of hippocampal synaptic plasticity

The naturally occurring fluctuation in estrogens that occurs across the estrous cycle can dramatically influence the morphology of the hippocampus in female rats. For example estrogens influence the density of dendritic spines in the CA1 region of the hippocampus. Dendritic spines can be classified by their shape into filopodial, thin, stubby, fenestrated or mushroom-shaped spines [143]. Small spines (filopodial and thin) have small head diameters and may be associated with learning processes

Influence of estrogens on cognition

The role of estrogens in eliciting and maintaining reproductive behaviors is well established in the literature. Recently the effects of estrogens on non-reproductive behaviors, such as cognition, have moved to the forefront of research [156]. The relationship between estrogens and cognition is immensely complex and depends on many factors each of which requires unique consideration. These factors include the brain structures and memory systems being recruited by the cognitive task [164], [165]

Conclusions

Endogenous and exogenous fluctuations in estrogens influence neuroplasticity and function of the hippocampus throughout the lifespan. Specifically adult hippocampal neurogenesis in female rats responds to estrogens throughout the lifespan, in a time- and dose-dependent manner. Many of estrogens' effects on the hippocampus are attributed to activation of classical estrogen receptors α and β, although more recent work also implicates nonclassical receptors in the hippocampus. Estrogens rapidly

Acknowledgments

Cindy Barha is a Michael Smith Senior Graduate Studentship. Research from our laboratory reviewed in this paper was made possible by operating grants from NSERC, CIHR and PARF (Pacific Alzheimer Research Foundation). LAMG is a Michael Smith Senior Scholar.

References (215)

  • C. Westenbroek et al.

    Chronic stress and social housing differentially affect neurogenesis in male and female rats

    Brain Res. Bull.

    (2004)
  • S.D. Kuipers et al.

    Unique patterns of FOS, phospho-CREB and BrdU immunoreactivity in the female rat brain following chronic stress and citalopram treatment

    Neuropharmacology

    (2006)
  • E.T. Rolls et al.

    A computational theory of hippocampal function, and empirical tests of the theory

    Prog. Neurobiol.

    (2006)
  • J.B. Aimone et al.

    Computational influence of adult neurogenesis on memory encoding

    Neuron

    (2009)
  • M. Butz et al.

    A theoretical network model to analyse neurogenesis and synaptogenesis in the dentate gyrus

    Neural Netw.

    (2006)
  • J.S. Snyder et al.

    A role for adult neurogenesis in spatial long-term memory

    Neuroscience

    (2005)
  • B. Vollmayr et al.

    Reduced cell proliferation in the dentate gyrus is not correlated with the development of learned helplessness

    Biol. Psychiatry

    (2003)
  • A.D. Green et al.

    Adult hippocampal cell proliferation is suppressed with estrogen withdrawal after a hormone-simulated pregnancy

    Horm. Behav.

    (2008)
  • G.J. Huang et al.

    Stimulation of neurogenesis in the hippocampus of the adult rat by fluoxetine requires rhythmic change in corticosterone

    Biol. Psychiatry

    (2006)
  • S.P. Herrick et al.

    Extranuclear estrogen receptor beta immunoreactivity is on doublecortin-containing cells in the adult and neonatal rat dentate gyrus

    Brain Res.

    (2006)
  • C.A. Mazzucco et al.

    Both estrogen receptor alpha and estrogen receptor beta agonists enhance cell proliferation in the dentate gyrus of adult female rats

    Neuroscience

    (2006)
  • C. Isgor et al.

    Estrogen receptor alpha and beta mRNA expressions by proliferating and differentiating cells in the adult rat dentate gyrus and subventricular zone

    Neuroscience

    (2005)
  • Z. Jonasson

    Meta-analysis of sex differences in rodent models of learning and memory: a review of behavioral and biological data

    Neurosci. Biobehav. Rev.

    (2005)
  • M.M. McCarthy et al.

    When is a sex difference not a sex difference?

    Front. Neuroendocrinol.

    (2005)
  • J.L. Pawluski et al.

    Effects of steroid hormones on neurogenesis in the hippocampus of the adult female rodent during the estrous cycle, pregnancy, lactation and aging

    Front. Neuroendocrinol.

    (2009)
  • B.K. Ormerod et al.

    Reproductive status influences cell proliferation and cell survival in the dentate gyrus of adult female meadow voles: a possible regulatory role for estradiol

    Neuroscience

    (2001)
  • J.S. Rosenblatt et al.

    Hormonal basis during pregnancy for the onset of maternal behavior in the rat

    Psychoneuroendocrinology

    (1988)
  • E. Gascon et al.

    Polysialic acid-neural cell adhesion molecule in brain plasticity: from synapses to integration of new neurons

    Brain Res. Rev.

    (2007)
  • M. Furuta et al.

    Gestation-induced cell proliferation in the rat brain

    Brain Res. Dev. Brain Res.

    (2005)
  • L.A. Galea et al.

    Spatial working memory and hippocampal size across pregnancy in rats

    Horm. Behav.

    (2000)
  • M. Darnaudery et al.

    Early motherhood in rats is associated with a modification of hippocampal function

    Psychoneuroendocrinology

    (2007)
  • J.L. Pawluski et al.

    Reproductive experience alters hippocampal neurogenesis during the postpartum period in the dam

    Neuroscience

    (2007)
  • J.L. Pawluski et al.

    Reproductive experience differentially affects spatial reference and working memory performance in the mother

    Horm. Behav.

    (2006)
  • J.L. Pawluski et al.

    First reproductive experience persistently affects spatial reference and working memory in the mother and these effects are not due to pregnancy or ‘mothering’ alone

    Behav. Brain Res.

    (2006)
  • J.D. Gatewood et al.

    Motherhood mitigates aging-related decrements in learning and memory and positively affects brain aging in the rat

    Brain Res. Bull.

    (2005)
  • M.F. Montaron et al.

    Lifelong corticosterone level determines age-related decline in neurogenesis and memory

    Neurobiol. Aging

    (2006)
  • N.R. Nichols et al.

    Do glucocorticoids contribute to brain aging?

    Brain Res. Brain Res. Rev.

    (2001)
  • L.A. Galea et al.

    Gonadal hormone modulation of hippocampal neurogenesis in the adult

    Hippocampus

    (2006)
  • L.A. Galea et al.

    Endocrine regulation of cognition and neuroplasticity: our pursuit to unveil the complex interaction between hormones, the brain, and behaviour

    Can. J. Exp. Psychol. = Revue canadienne de psychologie experimentale

    (2008)
  • E. Gould et al.

    Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation

    J. Neurosci.

    (1997)
  • P.S. Eriksson et al.

    Neurogenesis in the adult human hippocampus

    Nat. Med.

    (1998)
  • P. Lavenex et al.

    The seasonal pattern of cell proliferation and neuron number in the dentate gyrus of wild adult eastern grey squirrels

    Eur. J. NeuroSci.

    (2000)
  • E. Gould et al.

    Adult-generated hippocampal and neocortical neurons in macaques have a transient existence

    Proc. Natl Acad. Sci. USA

    (2001)
  • I. Amrein et al.

    Marked species and age-dependent differences in cell proliferation and neurogenesis in the hippocampus of wild-living rodents

    Hippocampus

    (2004)
  • I. Amrein et al.

    Absent or low rate of adult neurogenesis in the hippocampus of bats (Chiroptera)

    PloS one

    (2007)
  • F.H. Gage

    Mammalian neural stem cells

    Science

    (2000)
  • D. van der Kooy et al.

    Why stem cells?

    Science

    (2000)
  • M.D. Spritzer et al.

    Testosterone and dihydrotestosterone, but not estradiol, enhance survival of new hippocampal neurons in adult male rats

    Developmental neurobiology

    (2007)
  • J.E. Malberg et al.

    Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus

    J. Neurosci.

    (2000)
  • A.K. Olson et al.

    Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways

    Hippocampus

    (2006)
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