The evolving role of dendritic spines and memory: Interaction(s) with estradiol

Frankfurt, Maya; Luine, Victoria N.

doi:10.1016/j.yhbeh.2015.05.004

Cited by 129 publications

(86 citation statements)

References 108 publications

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“…Dysfunction of synaptic connections is recognized as the cause of memory impairments, and significant synapse loss has been observed in mild cognitive impairment (MCI) and in earlier stages of AD (8). In AD mouse models, synapse impairments appear before the onset of memory deficit (9), whereas amelioration of synapse loss by administration of estradiol preserves cognitive functions (10). Earlier investigations into AD-related synaptic damages have been mainly focused on the toxic effects of Aβ (11).…”

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confidence: 99%

Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling

Yin

Gao

Wang

et al. 2016

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

147

119

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Intracellular accumulation of wild-type tau is a hallmark of sporadic Alzheimer's disease (AD), but the molecular mechanisms underlying tau-induced synapse impairment and memory deficit are poorly understood. Here we found that overexpression of human wild-type full-length tau (termed hTau) induced memory deficits with impairments of synaptic plasticity. Both in vivo and in vitro data demonstrated that hTau accumulation caused remarkable dephosphorylation of cAMP response element binding protein (CREB) in the nuclear fraction. Simultaneously, the calcium-dependent protein phosphatase calcineurin (CaN) was up-regulated, whereas the calcium/ calmodulin-dependent protein kinase IV (CaMKIV) was suppressed. Further studies revealed that CaN activation could dephosphorylate CREB and CaMKIV, and the effect of CaN on CREB dephosphorylation was independent of CaMKIV inhibition. Finally, inhibition of CaN attenuated the hTau-induced CREB dephosphorylation with improved synapse and memory functions. Together, these data indicate that the hTau accumulation impairs synapse and memory by CaN-mediated suppression of nuclear CaMKIV/CREB signaling. Our findings not only reveal new mechanisms underlying the hTau-induced synaptic toxicity, but also provide potential targets for rescuing tauopathies.is the most common neurodegenerative disorder characterized clinically by progressive memory loss (1). The extracellular precipitation of β-amyloid (Aβ) (2), intracellular tau accumulation forming neurofibrillary tangles (3), and profound synapse degeneration are hallmark pathologies in AD brains (4, 5). Studies show that formation of neurofibrillary tangles is positively correlated with the degree of dementia symptoms (6), and the Aβ toxicity needs the presence of tau (7). These data suggest a crucial role of tau accumulation in neurodegeneration and the cognitive impairments in patients with AD. As a cytoskeleton protein, how tau accumulation causes memory deficits is not fully understood.Synapse is the fundamental unit for learning and memory. Dysfunction of synaptic connections is recognized as the cause of memory impairments, and significant synapse loss has been observed in mild cognitive impairment (MCI) and in earlier stages of AD (8). In AD mouse models, synapse impairments appear before the onset of memory deficit (9), whereas amelioration of synapse loss by administration of estradiol preserves cognitive functions (10). Earlier investigations into AD-related synaptic damages have been mainly focused on the toxic effects of Aβ (11). Recently, an emerging role of tau in synaptic impairment has been shown (12). For instance, overexpression of human mutant tau in mice induces synaptic degeneration even in the absence of tangles (13, 14) and reducing endogenous tau in mouse models carrying the mutated amyloid precursor protein (APP) prevents the cognitive deficits and synaptic loss (15).Among many structural or functional proteins involved in synapse development and memory formation, cAMP response element binding protein (CREB) is...

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confidence: 99%

Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling

Yin

Gao

Wang

et al. 2016

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

147

119

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“…Nevertheless, it is important that investigators consider the possible effects of sex steroid hormones on neural function and behavior in their experimental designs and data interpretation. However, when thinking about sex differences in brain function or behavior, it is important to note whether differences are due to the activational effects of circulating hormones in adulthood or from organizational effects of hormones in early development, as it has been argued that only the latter can be construed as a true sex difference (McCarthy and Konkle 2005).Numerous recent reviews have discussed the effects of E 2 on learning and memory in females (Korol 2002;Foster 2005;Daniel 2006Daniel , 2013Sherwin and Henry 2008;Barha and Galea 2010;Bimonte-Nelson et al 2010;Gibbs 2010;Kim and Casadesus 2010;Choleris et al 2012;Foster 2012;Frick 2012;Acosta et al 2013;Chisolm and Juraska 2013;Ervin et al 2013;Galea et al 2013;Hogervorst 2013;Luine and Frankfurt 2013;Maki 2013;Bean et al 2014;Luine 2014;Frankfurt and Luine 2015;Tuscher et al 2015). As such, this review will not attempt to provide a comprehensive discussion of all effects of E 2 on learning and memory.…”

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confidence: 99%

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

et al. 2015

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Ample evidence has demonstrated that sex steroid hormones, such as the potent estrogen 17b-estradiol (E 2 ), affect hippocampal morphology, plasticity, and memory in male and female rodents. Yet relatively few investigators who work with male subjects consider the effects of these hormones on learning and memory. This review describes the effects of E 2 on hippocampal spinogenesis, neurogenesis, physiology, and memory, with particular attention paid to the effects of E 2 in male rodents. The estrogen receptors, cell-signaling pathways, and epigenetic processes necessary for E 2 to enhance memory in female rodents are also discussed in detail. Finally, practical considerations for working with female rodents are described for those investigators thinking of adding females to their experimental designs.Hormones have long been known to play key roles in regulating learning and memory. Many hormones, including epinephrine, glucocorticoids, and insulin influence learning and memory via inverted U-shaped dose-response relationships in which memory is enhanced by moderate, but not low or high, hormone levels (Roozendaal 2000;Korol and Gold 2007;McNay and Recknagel 2011). Research from the past two decades has demonstrated that sex steroid hormones, particularly the potent estrogen 17b-estradiol (E 2 ), also regulate learning and memory in male and female rodents via an inverted U-shaped dose-response function that is influenced by estrogen receptor expression (Packard and Teather 1997a;Packard 1998;Foster 2012). Yet E 2 has not gained widespread acceptance as a hormonal modulator of memory in both females and males, perhaps because the majority of this research has been conducted in female rodents. Moreover, the common view of E 2 as a "female" hormone may contribute to the misperception that E 2 is not relevant for cognitive function in males. However, considerable evidence supports a vital role for E 2 in mediating neural function and behavior in male rodents. Therefore, it is important for investigators working with males to understand the ways in which E 2 and other sex steroid hormones (e.g., androgens, progestins, and other estrogens) may influence their brain regions and behaviors of interest.Another reason for investigators to be cognizant of sex steroid hormone-induced regulation of learning and memory is that males and females may respond differently to various treatments and environmental factors. A classic example is that of acute stress, which enhances classical conditioning and increases apical CA1 dendritic spine density in male rats, but impairs classical conditioning and decreases CA1 spine density in female rats (Wood and Shors 1998;Shors et al. 2001). Therefore, investigators hoping to comply with National Institutes of Health policies that encourage the inclusion of females in biomedical research must be aware that adding females to a study is not as simple as adding another group. In some ways, females are fundamentally different from males, the most obvious of which is the presence of reproductive...

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“…In ovariectomized rats, dendritic spine density in ventromedial hypothalamic nucleus (VMN), CA1 region on hippocampus, and medial prefrontal cortex is decreased as compared to gonadal intact rats. 30 The nervous system is capable of plasticity and that the dendritic spine is the major site of this activity. Statistical analysis showed that there was significantly increase the number of neurons after treatment in all groups (p<0.05), but the effect of tomato juice administration, physical exercise (swimming without resistance) and combination of these treatments showed the same effect (p>0.05) There was significant increase of ERβ expression after treatment in all groups (p<0.05) and each of the treatment was have the different effects (p<0.05).…”

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confidence: 99%

Tomato (Lycopersicum commune) Juice and Physical Exercise Increase Number of Neurons and ERβ expression in Post-Ovariectomy Rats Brain

et al. 2016

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Background: Estrogen deficiency condition can degrade the quality of life, decline in cognitive function will be more severe trough age. Phytoestrogen compounds can be found in pegaga leaf extract, tomatoes, and papaya is an easy and inexpensive way to increase estrogen levels in post menopause women through extra gonadal estrogen induction. Therefore, the aims of this study were to examine the effect of tomato juice, physical exercise, and combination of these treatments on promoting neurons and ERβ expression in somatosensory cortex that contribute to cognitive function of post-ovariectomy rats. Method: Twenty-eight female healthy Wistar rats (Rattus novergicus), 8-10 weeks old, from Laboratory of Biochemistry, Faculty of Medicine Airlangga University include in this experiment. The animals were housed in the animal-care facility with ad libitum food and water. The temperatur was maintained at 18°C-24°C. The treatments were done 2 weeks after ovariectomy. Tomato were made in Laboratory of Pharmacognocy and Phytochemistry, Faculty of Pharmacy, Airlangga University, from inner part of the tomato fruits (mucous like substance) with freeze dry method (-40°C). Results:The weight of white rat Rattus norvegicus post ovariectomy in this study was between 133-170 gram with a mean weight 154.32 ± 9.72 gram. Hematoxylin/eosin staining showed neuronal deficit in the control rats brain. In figure 1, the tomato group showed the largest of neurons number (145.43 ± 17.728), followed the combination group (140.57 ± 22.449), the exercise group (136.86 ± 23.104) and the smallest number in the control group (96.43± 28.965). Four weeks after treatments the number of neurons increased significant in the tomato group (p=0.001), exercise group (p=0.004) and combination group (p=0.002) from the control group. This study showed no significant different between tomato and exercise group (p=0.500), tomato and combination group (p=0.701) and between exercise and combination group (p=0.769). Conclusions:In conclusion, our data demonstrated that post ovariectomy rats showed deficit numbers of neurons and decreased ERβ in the somatosensory cortex. Treatment with physical exercise, tomato juice, and combination of these treatments increased the number of neurons and ERβ expression in the somatosensory cortex.

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The evolving role of dendritic spines and memory: Interaction(s) with estradiol

Cited by 129 publications

References 108 publications

Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling

Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling

Sex steroid hormones matter for learning and memory: estrogenic regulation of hippocampal function in male and female rodents

Tomato (Lycopersicum commune) Juice and Physical Exercise Increase Number of Neurons and ERβ expression in Post-Ovariectomy Rats Brain

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