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Mechanisms of estradiol in fear circuitry: implications for sex differences in psychopathology.

Cover KK, Maeng LY, Lebrón-Milad K, Milad MR - Transl Psychiatry (2014)

Bottom Line: Over the past two decades, substantial knowledge has been attained about the mechanisms underlying the acquisition and subsequent extinction of conditioned fear.Lacking in the current knowledge is how men and women may or may not differ in the biology of fear and its extinction.In this review, we begin by highlighting the epidemiological differences in incidence rate.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA.

ABSTRACT
Over the past two decades, substantial knowledge has been attained about the mechanisms underlying the acquisition and subsequent extinction of conditioned fear. Knowledge gained on the biological basis of Pavlovian conditioning has led to the general acceptance that fear extinction may be a useful model in understanding the underlying mechanisms in the pathophysiology of anxiety disorders and may also be a good model for current therapies treating these disorders. Lacking in the current knowledge is how men and women may or may not differ in the biology of fear and its extinction. It is also unclear how the neural correlates of fear extinction may mediate sex differences in the etiology, maintenance, and prevalence of psychiatric disorders. In this review, we begin by highlighting the epidemiological differences in incidence rate. We then discuss how estradiol (E2), a primary gonadal hormone, may modulate the mechanisms of fear extinction and mediate some of the sex differences observed in psychiatric disorders.

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Relative estrogen receptor distribution within the rat fear extinction network. Estrogen receptor alpha (ERα left) is expressed moderately in the ventromedial prefrontal cortex (vmPFC) and hippocampus and strongly in the amygdala. Estrogen receptor beta (ERβ right) is weakly expressed in the vmPFC and amygdala and strongly in the hippocampus. These relative distributions are compiled from studies employing immunoreactivity and in situ hybridization methodologies.51,52,55,56, 57, 58 Atlas images are adapted from Paxinos and Watson.59
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fig3: Relative estrogen receptor distribution within the rat fear extinction network. Estrogen receptor alpha (ERα left) is expressed moderately in the ventromedial prefrontal cortex (vmPFC) and hippocampus and strongly in the amygdala. Estrogen receptor beta (ERβ right) is weakly expressed in the vmPFC and amygdala and strongly in the hippocampus. These relative distributions are compiled from studies employing immunoreactivity and in situ hybridization methodologies.51,52,55,56, 57, 58 Atlas images are adapted from Paxinos and Watson.59

Mentions: E2 acts primarily through estrogen receptor subtypes alpha (ERα) and beta (ERβ). ERα is functionally related with reproductive behavior48 whereas ERβ is associated with nonreproductive behaviors such as learning and memory49 and anxiety-related behaviors.50 These receptors are expressed throughout the brain and may localize in the nucleus, cytoplasm and cell membrane.43 The ERs have similar distribution in male and female brains but may differ in relative expression.51,52 ERα and ERβ expression patterns generally overlap, though ERα dominates hypothalamic subregions53 whereas ERβ is more abundant in the hippocampus52 and cerebral cortex.54 The ERs show distinct expression within the amygdala subregions, however, ERα is the predominate receptor.51,55 Regarding the vmPFC, both ERα and ERβ have been detected in the rat IL and prelimbic cortex.56, 57, 58 A summary of relative receptor distribution within the fear extinction network is illustrated in Figure 3.


Mechanisms of estradiol in fear circuitry: implications for sex differences in psychopathology.

Cover KK, Maeng LY, Lebrón-Milad K, Milad MR - Transl Psychiatry (2014)

Relative estrogen receptor distribution within the rat fear extinction network. Estrogen receptor alpha (ERα left) is expressed moderately in the ventromedial prefrontal cortex (vmPFC) and hippocampus and strongly in the amygdala. Estrogen receptor beta (ERβ right) is weakly expressed in the vmPFC and amygdala and strongly in the hippocampus. These relative distributions are compiled from studies employing immunoreactivity and in situ hybridization methodologies.51,52,55,56, 57, 58 Atlas images are adapted from Paxinos and Watson.59
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150242&req=5

fig3: Relative estrogen receptor distribution within the rat fear extinction network. Estrogen receptor alpha (ERα left) is expressed moderately in the ventromedial prefrontal cortex (vmPFC) and hippocampus and strongly in the amygdala. Estrogen receptor beta (ERβ right) is weakly expressed in the vmPFC and amygdala and strongly in the hippocampus. These relative distributions are compiled from studies employing immunoreactivity and in situ hybridization methodologies.51,52,55,56, 57, 58 Atlas images are adapted from Paxinos and Watson.59
Mentions: E2 acts primarily through estrogen receptor subtypes alpha (ERα) and beta (ERβ). ERα is functionally related with reproductive behavior48 whereas ERβ is associated with nonreproductive behaviors such as learning and memory49 and anxiety-related behaviors.50 These receptors are expressed throughout the brain and may localize in the nucleus, cytoplasm and cell membrane.43 The ERs have similar distribution in male and female brains but may differ in relative expression.51,52 ERα and ERβ expression patterns generally overlap, though ERα dominates hypothalamic subregions53 whereas ERβ is more abundant in the hippocampus52 and cerebral cortex.54 The ERs show distinct expression within the amygdala subregions, however, ERα is the predominate receptor.51,55 Regarding the vmPFC, both ERα and ERβ have been detected in the rat IL and prelimbic cortex.56, 57, 58 A summary of relative receptor distribution within the fear extinction network is illustrated in Figure 3.

Bottom Line: Over the past two decades, substantial knowledge has been attained about the mechanisms underlying the acquisition and subsequent extinction of conditioned fear.Lacking in the current knowledge is how men and women may or may not differ in the biology of fear and its extinction.In this review, we begin by highlighting the epidemiological differences in incidence rate.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry, Massachusetts General Hospital, Charlestown, MA, USA.

ABSTRACT
Over the past two decades, substantial knowledge has been attained about the mechanisms underlying the acquisition and subsequent extinction of conditioned fear. Knowledge gained on the biological basis of Pavlovian conditioning has led to the general acceptance that fear extinction may be a useful model in understanding the underlying mechanisms in the pathophysiology of anxiety disorders and may also be a good model for current therapies treating these disorders. Lacking in the current knowledge is how men and women may or may not differ in the biology of fear and its extinction. It is also unclear how the neural correlates of fear extinction may mediate sex differences in the etiology, maintenance, and prevalence of psychiatric disorders. In this review, we begin by highlighting the epidemiological differences in incidence rate. We then discuss how estradiol (E2), a primary gonadal hormone, may modulate the mechanisms of fear extinction and mediate some of the sex differences observed in psychiatric disorders.

Show MeSH
Related in: MedlinePlus