Regulation of synaptic plasticity by hippocampus synthesized estradiol

2011 ◽  
Vol 7 (2) ◽  
Author(s):  
Anna M. Barron ◽  
Yasushi Hojo ◽  
Hideo Mukai ◽  
Shimpei Higo ◽  
Yuuki Ooishi ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Decline ◽  
Estrogen Receptors ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Adult Rats ◽  
Age Related ◽  
Estradiol Synthesis ◽  
Age Related Cognitive Decline

AbstractEstradiol is synthesized from cholesterol in hippocampal neurons of adult rats by cytochrome P450 and hydroxysteroid dehydrogenase enzymes. These enzymes are expressed in the glutamatergic neurons of the hippocampus. Surprisingly, the concentration of estradiol and androgen in the hippocampus is significantly higher than that in circulation. Locally synthesized estradiol rapidly and potently modulates synaptic plasticity within the hippocampus. E2 rapidly potentiates long-term depression and induces spinogenesis through synaptic estrogen receptors and kinases. The rapid effects of estradiol are followed by slow genomic effects mediated by both estrogen receptors located at the synapse and nucleus, modulating long-term potentiation and promoting the formation of new functional synaptic contacts. Age-related changes in hippocampally derived estradiol synthesis and distribution of estrogen receptors may alter synaptic plasticity, and could potentially contribute to age-related cognitive decline. Understanding factors which regulate hippocampal estradiol synthesis could lead to the identification of alternatives to conventional hormone therapy to protect against age-related cognitive decline.

scholarly journals Aging Effects on the Limits and Stability of Long-Term Synaptic Potentiation and Depression in Rat Hippocampal Area CA1

2007 ◽  
Vol 98 (2) ◽  
pp. 594-601 ◽  
Author(s):  
Ashok Kumar ◽  
Jeffrey S. Thinschmidt ◽  
Thomas C. Foster ◽  
Michael A. King
Keyword(s):  
Synaptic Plasticity ◽  
Young Adult ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Brown Norway ◽  
Aging Effects ◽  
Adult Rats ◽  
Age Related ◽  
Significant Difference

Altered hippocampal synaptic plasticity may underlie age-related memory impairment. In acute hippocampal slices from aged (22–24 mo) and young adult (1–12 mo) male Brown Norway rats, extracellular excitatory postsynaptic field potentials were recorded in CA1 stratum radiatum evoked by Schaffer collateral stimulation. We used enhanced Ca2+ to Mg2+ ratio and paired-pulse stimulation protocol to induce maximum changes in the synaptic plasticity. Six episodes of theta-burst stimulation (TBS) or nine episodes of paired low-frequency stimulation (pLFS) were used to generate asymptotic long-term potentiation (LTP) and long-term depression (LTD), respectively. In addition, long-term depotentiation (LTdeP) or de-depression (LTdeD) from maximal LTP and LTD were examined using two episodes of pLFS or TBS. Multiple episodes of TBS or pLFS produced significant LTP or LTD in aged and young adult rats; this was not different between age groups. Moreover, there was no significant difference in the amount of LTdeP or LTdeD between aged and young adult rats. Our results show no age differences in the asymptotic magnitude of LTP or LTD, rate of synaptic modifications, development rates, reversal, or decay after postconditioning. Thus impairment of the basic synaptic mechanisms responsible for expression of these forms of plasticity is not likely to account for decline in memory function within this age range.

scholarly journals Hippocampal dysregulation of synaptic plasticity-associated proteins with age-related cognitive decline

2011 ◽  
Vol 43 (1) ◽  
pp. 201-212 ◽  
Author(s):  
Heather D. VanGuilder ◽  
Julie A. Farley ◽  
Han Yan ◽  
Colleen A. Van Kirk ◽  
Matthew Mitschelen ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Cognitive Decline ◽  
Age Related ◽  
Associated Proteins ◽  
Age Related Cognitive Decline

scholarly journals Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions

2014 ◽  
pp. 309 ◽  
Author(s):  
Cristovam Picanço-Diniz ◽  
Thais Cristina Galdino De Oliveira ◽  
Fernanda Cabral Soares ◽  
Liliane Dias E Dias De Macedo ◽  
Domingos Luiz Wanderley Picanco Diniz ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Long Term Care ◽  
Cognitive Stimulation ◽  
Term Care ◽  
Beneficial Effects ◽  
Age Related ◽  
Age Related Cognitive Decline

scholarly journals Age-Related Cognitive Impairment: Role of Reduced Synaptobrevin-2 Levels in Deficits of Memory and Synaptic Plasticity

2019 ◽  
Vol 75 (9) ◽  
pp. 1624-1632 ◽  
Author(s):  
Albert Orock ◽  
Sreemathi Logan ◽  
Ferenc Deak
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Receptor Protein ◽  
Protein Levels ◽  
Ca1 Region ◽  
Age Related ◽  
Term Potentiation

AbstractCognitive impairment in the aging population is quickly becoming a health care priority, for which currently no disease-modifying treatment is available. Multiple domains of cognition decline with age even in the absence of neurodegenerative diseases. The cellular and molecular changes leading to cognitive decline with age remain elusive. Synaptobrevin-2 (Syb2), the major vesicular SNAP receptor protein, highly expressed in the cerebral cortex and hippocampus, is essential for synaptic transmission. We have analyzed Syb2 protein levels in mice and found a decrease with age. To investigate the functional consequences of lower Syb2 expression, we have used adult Syb2 heterozygous mice (Syb2+/−) with reduced Syb2 levels. This allowed us to mimic the age-related decrease of Syb2 in the brain in order to selectively test its effects on learning and memory. Our results show that Syb2+/− animals have impaired learning and memory skills and they perform worse with age in the radial arm water maze assay. Syb2+/− hippocampal neurons have reduced synaptic plasticity with reduced release probability and impaired long-term potentiation in the CA1 region. Syb2+/− neurons also have lower vesicular release rates when compared to WT controls. These results indicate that reduced Syb2 expression with age is sufficient to cause cognitive impairment.

scholarly journals Chemical LTD, but not LTP, induces transient accumulation of gelsolin in dendritic spines

2019 ◽  
Vol 400 (9) ◽  
pp. 1129-1139 ◽  
Author(s):  
Iryna Hlushchenko ◽  
Pirta Hotulainen
Keyword(s):  
Synaptic Plasticity ◽  
Dendritic Spines ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Excitatory Synapses ◽  
Signal Molecule ◽  
Brain Functions ◽  
Dendritic Shaft ◽  
Term Potentiation

Abstract Synaptic plasticity underlies central brain functions, such as learning. Ca2+ signaling is involved in both strengthening and weakening of synapses, but it is still unclear how one signal molecule can induce two opposite outcomes. By identifying molecules, which can distinguish between signaling leading to weakening or strengthening, we can improve our understanding of how synaptic plasticity is regulated. Here, we tested gelsolin’s response to the induction of chemical long-term potentiation (cLTP) or long-term depression (cLTD) in cultured rat hippocampal neurons. We show that gelsolin relocates from the dendritic shaft to dendritic spines upon cLTD induction while it did not show any relocalization upon cLTP induction. Dendritic spines are small actin-rich protrusions on dendrites, where LTD/LTP-responsive excitatory synapses are located. We propose that the LTD-induced modest – but relatively long-lasting – elevation of Ca2+ concentration increases the affinity of gelsolin to F-actin. As F-actin is enriched in dendritic spines, it is probable that increased affinity to F-actin induces the relocalization of gelsolin.

scholarly journals Age-Related Alterations in the Expression of Genes and Synaptic Plasticity Associated with Nitric Oxide Signaling in the Mouse Dorsal Striatum

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Aisa N. Chepkova ◽  
Susanne Schönfeld ◽  
Olga A. Sergeeva
Keyword(s):  
Nitric Oxide ◽  
Synaptic Plasticity ◽  
Metabotropic Glutamate Receptors ◽  
Dorsal Striatum ◽  
Long Term Potentiation ◽  
Striatal Slices ◽  
Expression Of Genes ◽  
Age Related ◽  
Group I

Age-related alterations in the expression of genes and corticostriatal synaptic plasticity were studied in the dorsal striatum of mice of four age groups from young (2-3 months old) to old (18–24 months of age) animals. A significant decrease in transcripts encoding neuronal nitric oxide (NO) synthase and receptors involved in its activation (NR1 subunit of the glutamate NMDA receptor and D1 dopamine receptor) was found in the striatum of old mice using gene array and real-time RT-PCR analysis. The old striatum showed also a significantly higher number of GFAP-expressing astrocytes and an increased expression of astroglial, inflammatory, and oxidative stress markers. Field potential recordings from striatal slices revealed age-related alterations in the magnitude and dynamics of electrically induced long-term depression (LTD) and significant enhancement of electrically induced long-term potentiation in the middle-aged striatum (6-7 and 12-13 months of age). Corticostriatal NO-dependent LTD induced by pharmacological activation of group I metabotropic glutamate receptors underwent significant reduction with aging and could be restored by inhibition of cGMP hydrolysis indicating that its age-related deficit is caused by an altered NO-cGMP signaling cascade. It is suggested that age-related alterations in corticostriatal synaptic plasticity may result from functional alterations in receptor-activated signaling cascades associated with increasing neuroinflammation and a prooxidant state.

scholarly journals Human Cytomegalovirus Immediate Early Protein 2 Protein Causes Cognitive Disorder by Damaging Synaptic Plasticity in Human Cytomegalovirus-UL122-Tg Mice

2021 ◽  
Vol 13 ◽  
Author(s):  
Zhifei Wang ◽  
Wenwen Yu ◽  
Lili Liu ◽  
Junyun Niu ◽  
Xianjuan Zhang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
Human Cytomegalovirus ◽  
Hippocampal Neurons ◽  
Long Term Potentiation ◽  
Cognitive Disorder ◽  
Immediate Early ◽  
Early Protein ◽  
Old Mice

Human cytomegalovirus (HCMV) infection is very common in the human population all around the world. Although the majority of HCMV infections are asymptomatic, they can cause neurologic deficits. Previous studies have shown that immediate early protein 2 (IE2, also known as UL122) of HCMV is related with the cognitive disorder mechanism. Due to species isolation, a HCMV-infected animal model could not be established which meant a study into the long-term effects of IE2 on neural development could not be carried out. By establishing HCMV-UL122-Tg mice (UL122 mice), we explored the cognitive behavior and complexity of neuron changes in this transgenic UL122 mice that could consistently express IE2 protein at different ages (confirmed in both 6- and 12-month-old UL122 mice). In the Morris water maze, cognitive impairment was more pronounced in 12-month-old UL122 mice than in 6-month-old ones. At the same time, a decrease of the density of dendritic spines and branches in the hippocampal neurons of 12-month-old mice was observed. Moreover, long-term potentiation was showed to be impaired in 12-month-old UL122 mice. The expressions of several synaptic plasticity-regulated molecules were reduced in 12-month-old UL122 mice, including scaffold proteins postsynaptic density protein 95 (PSD95) and microtubule-associated protein 2 (MAP2). Binding the expression of IE2 was increased in 12-month-old mice compared with 6-month-old mice, and results of statistical analysis suggested that the cognitive damage was not caused by natural animal aging, which might exclude the effect of natural aging on cognitive impairment. All these results suggested that IE2 acted as a pathogenic regulator in damaging synaptic plasticity by downregulating the expression of plasticity-related proteins (PRPs), and this damage increased with aging.

Enhanced Long-Term Potentiation During Aging Is Masked by Processes Involving Intracellular Calcium Stores

2004 ◽  
Vol 91 (6) ◽  
pp. 2437-2444 ◽  
Author(s):  
Ashok Kumar ◽  
Thomas C. Foster
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Calcium Stores ◽  
Age Related ◽  
Term Potentiation ◽  
Pattern Stimulation ◽  
Old Rats

The contribution of Ca2+ release from intracellular Ca2+ stores (ICS) for regulation of synaptic plasticity thresholds during aging was investigated in hippocampal slices of old (22–24 mo) and young adult (5–8 mo) male Fischer 344 rats. Inhibition of Ca2+-induced Ca2+ release by thapsigargin, cyclopiazonic acid (CPA), or ryanodine during pattern stimulation near the threshold for synaptic modification (5 Hz, 900 pulses) selectively induced long-term potentiation (LTP) to CA1 Schaffer collateral synapses of old rats. Increased synaptic strength was specific to test pathways and blocked by AP-5. Intracellular recordings demonstrated that ICS plays a role in the augmentation of the afterhyperpolarization (AHP) in old rats. The decrease in the AHP by ICS inhibition was reversed by the L-channel agonist, Bay K8644. Under conditions of ICS inhibition and a Bay K8644–mediated enhancement of the AHP, pattern stimulation failed to induce LTP, consistent with the idea that the AHP amplitude shapes the threshold for LTP induction. Finally, ICS inhibition was associated with an increase in the N-methyl-d-aspartate (NMDA) receptor component of synaptic transmission in old animals. This increase in the synaptic response was blocked by the calcineurin inhibitor FK506. The results reveal an age-related increase in susceptibility to LTP-induction that is normally inhibited by ICS and suggest that the age-related shift in Ca2+ regulation and Ca2+-dependent synaptic plasticity is coupled to changes in cell excitability and NMDA receptor function through ICS.

scholarly journals Thinking through acidic Ca2+ stores

2018 ◽  
Vol 11 (558) ◽  
pp. eaau3342
Author(s):  
Sandip Patel ◽  
Eugen Brailoiu
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Activity ◽  
Hippocampal Neurons ◽  
Metabotropic Glutamate Receptors ◽  
Long Term Potentiation ◽  
Glutamate Signaling ◽  
Metabotropic Glutamate ◽  
Term Potentiation ◽  
Intracellular Messenger

Glutamate signaling regulates neuronal activity and synaptic plasticity, which underlies learning and memory. In this issue of Science Signaling, Foster et al. found that metabotropic glutamate receptors mediate long-term potentiation in hippocampal neurons by mobilizing acidic endolysosomal Ca2+ stores through the intracellular messenger NAADP.

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