Evolving Knowledge of Sex Differences in Brain Structure, Function, and Chemistry

Cosgrove, Kelly P.; Mazure, Carolyn M.; Staley, Julie K.

doi:10.1016/j.biopsych.2007.03.001

Cited by 850 publications

(635 citation statements)

References 96 publications

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“…Other sex differences in learning are mediated by the presence of sex hormones and sex differences in the structure of the brain (27,28,(39)(40)(41). As presented here, the total volume of the dentate gyrus is greater in males than in females (27,42).…”

Section: Discussionmentioning

confidence: 49%

Female rats learn trace memories better than male rats and consequently retain a greater proportion of new neurons in their hippocampi

Dalla

Papachristos

Whetstone

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

106

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Learning increases the survival of new cells that are generated in the hippocampal formation before the training experience, especially if the animal learns to associate stimuli across time [Gould E, Beylin A, Tanapat P, Reeves A, Shors TJ (1999) Nat Neurosci 2:260 -265]. All relevant studies have been conducted on male rats, despite evidence for sex differences in this type of learning. In the present study, we asked whether sex differences in learning influence the survival of neurons generated in the adult hippocampus. Male and female adult rats were injected with one dose of bromodeoxyuridine (BrdU; 200 mg/kg), to label one population of dividing cells. One week later, half of the animals were trained with a temporal learning task of trace eyeblink conditioning, while the other half were not trained. Animals were killed 1 day after training (12 days after the BrdU injection). Hippocampal tissue was stained for BrdU and a marker of immature neurons, doublecortin. Both sexes learned to emit the conditioned eyeblink response during the trace interval. As a consequence, more new neurons remained in their hippocampi than in sex-matched controls. In individual animals, the number of surviving cells correlated positively with asymptotic performance; those that expressed more learned responses retained more new neurons. However, animals that learned very well retained even more new cells if they required many trials to do so. Because females emitted more learned responses than males did, they retained nearly twice as many new cells per unit volume of tissue. This effect was most evident in the ventral region of the hippocampal formation. Thus, sex differences in learning alter the anatomical structure of the hippocampus. As a result, male and female brains continue to differentiate in adulthood.eyeblink conditioning ͉ learning ͉ neurogenesis ͉ sex differences ͉ stem cell

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Section: Discussionmentioning

confidence: 49%

Female rats learn trace memories better than male rats and consequently retain a greater proportion of new neurons in their hippocampi

Dalla

Papachristos

Whetstone

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

106

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“…The age and sex effects on 5-HT 4 receptor binding were assessed with PV-corrected data as the PV effect results in an underestimation of counts in high-count voxels because of spill-over to neighboring voxels due to insufficient resolution of the PET scanner. Amounts of spill-out and spill-in of brain regions depend on brain structure and are therefore influenced by the increased occurrence of brain atrophy with age (Raz et al, 2005) and the well-documented structural sex differences (Cosgrove et al, 2007).…”

Section: Pet Imaging and Quantification Of Nondisplaceable 5-ht 4 Recmentioning

confidence: 99%

Age and sex effects on 5-HT₄ receptors in the human brain: A [¹¹C]SB207145 PET study

Madsen

Haahr

Marner

et al. 2011

J Cereb Blood Flow Metab

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Experimental studies indicate that the 5-HT 4 receptor activation influence cognitive function, affective symptoms, and the development of Alzheimer's disease (AD). The prevalence of AD increases with aging, and women have a higher predisposition to both AD and affective disorders than men. This study aimed to investigate sex and age effects on 5-HT 4 receptor-binding potentials in striatum, the limbic system, and neocortex. Positron-emission tomographic scans were conducted using the radioligand [ 11 C]SB207145 in a cohort of 30 healthy subjects (mean age 44 years; range 20 to 86 years; 14 men and 16 women). The output parameter, BP ND , was modeled using the simplified reference tissue model, and partial volume correction was performed with the Muller-Gartner method. A decline with age of 1% per decade was found only in striatum. Women had a 13% lower 5-HT 4 receptor binding in the limbic system. The lower limbic 5-HT 4 receptor binding in women supports a role for 5-HT 4 receptors in the sex-specific differences in emotional control and might contribute to the higher prevalence of affective diseases and AD in women. The relatively stable 5-HT 4 receptor binding with aging contrasts others in subtypes of receptors, which generally decrease with aging.

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“…Cortical tissue dopamine concentrations are similar in men and women (Robinson et al, 1977), although women may have a higher extrastriatal D2 receptor-binding potential (Kaasinen et al, 2001). In summary, there are diverse data indicating sex differences in central dopaminergic parameters (see Cosgrove et al, 2007). However, it is not clear what their net effect is upon the dopamine system in men compared to women, nor how the dopaminergic sexual dimorphisms impinge upon the inverted U-shaped relationship between dopamine activity and prefrontal function (Goldman-Rakic et al, 2000) nor the modulatory effect that COMT has upon this relationship (Mattay et al, 2003;Tunbridge et al, 2006a;Williams-Gray et al, 2007).…”

Section: Mechanisms Of Sexual Dimorphism In Comt Effects and Associatmentioning

confidence: 99%

“…Sex is an important factor in neuroscience (Cahill, 2006) and psychiatry (Cosgrove et al, 2007). Many parameters of brain function and structure vary between men and women (eg Gur et al, 1995;Murphy et al, 1996;De Courten-Myers, 1999;De Bellis et al, 2001;Goldstein et al, 2001;Preece and Cairns, 2003;De Vries, 2004), and most psychiatric disorders show sex differences in one or more variables including incidence, age at onset, clinical features, and outcome (eg Lensi et al, 1996;Tamminga, 1997;Piccinelli and Wilkinson, 2000;Aleman et al, 2003;Baron-Cohen et al, 2005).…”

mentioning

confidence: 99%

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

Harrison

Tunbridge

2007

Neuropsychopharmacol

268

216

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Sex differences in the genetic epidemiology and clinical features of psychiatric disorders are well recognized, but the individual genes contributing to these effects have rarely been identified. Catechol-O-methyltransferase (COMT), which metabolizes catechol compounds, notably dopamine, is a leading candidate. COMT enzyme activity, and the neurochemistry and behavior of COMT null mice, are both markedly sexually dimorphic. Genetic associations between COMT and various psychiatric phenotypes frequently show differences between men and women. Many of these differences are unconfirmed or minor, but some appear to be of reasonable robustness and magnitude; eg the functional Val 158 Met polymorphism in COMT is associated with obsessive-compulsive disorder in men, with anxiety phenotypes in women, and has a greater impact on cognitive function in boys than girls. Sex-specific effects of COMT are usually attributed to transcriptional regulation by estrogens; however, additional mechanisms are likely to be at least as important. Here we review the evidence for a sexually dimorphic influence of COMT upon psychiatric phenotypes, and discuss its potential basis. We conclude that despite the evidence being incomplete, and lacking a unifying explanation, there are accumulating and in places compelling data showing that COMT differentially impacts on brain function and dysfunction in men and women. Since sex differences in the genetic architecture of quantitative traits are the rule not the exception, we anticipate that additional evidence will emerge for sexual dimorphisms, not only in COMT but also in many other autosomal genes.

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Evolving Knowledge of Sex Differences in Brain Structure, Function, and Chemistry

Cited by 850 publications

References 96 publications

Female rats learn trace memories better than male rats and consequently retain a greater proportion of new neurons in their hippocampi

Female rats learn trace memories better than male rats and consequently retain a greater proportion of new neurons in their hippocampi

Age and sex effects on 5-HT₄ receptors in the human brain: A [¹¹C]SB207145 PET study

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

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Evolving Knowledge of Sex Differences in Brain Structure, Function, and Chemistry

Cited by 850 publications

References 96 publications

Female rats learn trace memories better than male rats and consequently retain a greater proportion of new neurons in their hippocampi

Female rats learn trace memories better than male rats and consequently retain a greater proportion of new neurons in their hippocampi

Age and sex effects on 5-HT4 receptors in the human brain: A [11C]SB207145 PET study

Catechol-O-Methyltransferase (COMT): A Gene Contributing to Sex Differences in Brain Function, and to Sexual Dimorphism in the Predisposition to Psychiatric Disorders

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Age and sex effects on 5-HT₄ receptors in the human brain: A [¹¹C]SB207145 PET study