Influence of different estrogens on neuroplasticity and cognition in the hippocampus

doi:10.1016/j.bbagen.2010.01.006

Biochimica et Biophysica Acta (BBA) - General Subjects

Volume 1800, Issue 10, October 2010, Pages 1056-1067

https://doi.org/10.1016/j.bbagen.2010.01.006 Get rights and content

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.

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ReviewInfluence of different estrogens on neuroplasticity and cognition in the hippocampus

Abstract

Background

Scope of review

Major conclusions

General significance

Section snippets

What is adult neurogenesis and how to study it?

Influence of estrogens on other forms of hippocampal synaptic plasticity

Influence of estrogens on cognition

Conclusions

Acknowledgments

Hippocampus: cognitive processes and neural representations that underlie declarative memory

Neuron

Hippocampal formation: shedding light on the influence of sex and stress on the brain

Brain Res. Rev.

Gonadal hormone modulation of hippocampal neurogenesis in the adult

Hippocampus

Gonadal hormone modulation of neurogenesis in the dentate gyrus of adult male and female rodents

Brain Res. Rev.

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

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

J. Neurosci.

Neurogenesis in the adult human hippocampus

Nat. Med.

Progenitor cells in the adult zebrafish nervous system express a Brn-1-related POU gene, tai-ji

Mech. Dev.

Sex and seasonal differences in the rate of cell proliferation in the dentate gyrus of adult wild meadow voles

Neuroscience

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

Eur. J. NeuroSci.

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

Proc. Natl Acad. Sci. USA

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

Hippocampus

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

PloS one

Mammalian neural stem cells

Science

Why stem cells?

Science

Stem and progenitor cells: the premature desertion of rigorous definitions

Trends Neurosci.

Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat

Neuroscience

Hippocampus-dependent learning promotes survival of new neurons in the dentate gyrus at a specific time during cell maturation

Neuroscience

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

Developmental neurobiology

Repeated estradiol administration alters different aspects of neurogenesis and cell death in the hippocampus of female, but not male, rats

Neuroscience

Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus

J. Neurosci.

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

Hippocampus

BrdU immunohistochemistry for studying adult neurogenesis: paradigms, pitfalls, limitations, and validation

Brain Res. Rev.

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

Brain Res. Bull.

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

Neuropharmacology

Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus

J. Comp. Neurol.

Neurogenesis in the adult hippocampus

Hippocampus

Functional neurogenesis in the adult hippocampus

Nature

Rapid extension of axons into the CA3 region by adult-generated granule cells

J. Comp. Neurol.

Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus

J. Neurosci.

Adult-generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles

J. Comp. Neurol.

Neuronal differentiation in the adult hippocampus recapitulates embryonic development

J. Neurosci.

GABA regulates synaptic integration of newly generated neurons in the adult brain

Nature

Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus

Nature

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