CIDeRplusGeneral Information:
| Id: | 9,092 |
| Diseases: |
Developmental
Metabolic |
| Mammalia | |
| review | |
| Reference: | Anggono V et al.(2016) Glutamate Receptors in Alzheimers Disease: Mechanisms and Therapies Neural Plast. 2016 [PMID: 23238908] |
Interaction Information:
| Comment | The menopause transition is marked initially by fluctuating levels of ovarian hormones and ends with an overall dearth of estrogen in the postmenopausal period. |
|
Formal Description Interaction-ID: 95261 |
process menopause transition increases_activity of phenotype altered ovarian hormones |
| Comment | Optimal executive functioning and prefrontal cortex regulation of subcortical brain structures are dependent upon prefrontal concentrations of catecholamines, specifically dopamine (DA) and norepinephrine (NE). |
|
Formal Description Interaction-ID: 96242 |
drug/chemical compound affects_activity of tissue/cell line |
| Drugbank entries | Show/Hide entries for Dopamine |
| Comment | Serotonin (5-HT) and acetylcholine (ACh) are also important in prefrontal cortex neurochemical modulation of attention. |
|
Formal Description Interaction-ID: 96243 |
drug/chemical compound affects_activity of tissue/cell line |
| Comment | Dopamine (DA) and norepinephrine (NE), the catecholamines crucial for executive functioning, are modulated by estrogen in the prefrontal cortex. |
|
Formal Description Interaction-ID: 96245 |
drug/chemical compound Estrogen affects_activity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | Treatment with 17beta-estradiol both improved memory consolidation and affected dopaminergic, noradrenergic, and serotonergic neurotransmission in the rodent prefrontal cortex. |
|
Formal Description Interaction-ID: 96246 |
drug/chemical compound increases_activity of process memory consolidation |
| Drugbank entries | Show/Hide entries for Estradiol |
| Comment | Estrogen significantly raised concentrations of 5-HT, MHPG (3-Methoxy-4-Hydroxyphenylglycol, metabolite of NE), and DOPAC (3-4-dihydroxyphenylalanine, metabolite of DA) in the prefrontal cortex of rats OVXed at 55 to 60 days as well as the turnover rate of NE to MHPG shortly after treatment. |
|
Formal Description Interaction-ID: 96247 |
drug/chemical compound Estrogen increases_quantity of drug/chemical compound |
| Comment | Treatment with significantly higher or lower doses of 17beta-estradiol or higher doses of 17alpha-estradiol were found to be ineffective in improving spatial and non-spatial memory consolidation in OVX rats despite the increase in neurotransmitter levels that occurred at the higher doses, indicating that estrogen’s beneficial effects on cognition are dose dependent. |
|
Formal Description Interaction-ID: 96249 |
drug/chemical compound NOT affects_activity of process memory consolidation |
| Drugbank entries | Show/Hide entries for Estradiol |
| Comment | Estrogen also affects the neurotransmitter systems through enzymatic regulation of transmitter metabolism. |
|
Formal Description Interaction-ID: 96250 |
|
| Comment | Decreases in COMT (o-methyl transferase) protein expression and enzyme activity were observed in male rats receiving estrogen, suggesting sex differences in the effects of estrogen on dopamine metabolism. |
|
Formal Description Interaction-ID: 96251 |
phenotype sex, male decreases_expression of gene/protein |
| Drugbank entries | Show/Hide entries for COMT |
| Comment | Estradiol treatment initiated 5 months after OVX increased choline acetyltransferase (ChAT) protein levels in the PFC while the same treatment administered immediately following OVX did not, leading the authors to suggest that the period of hormone deprivation sensitized PFC cholinergic systems to the effects of estrogen (delay in prefrontal cortex sensitization). |
|
Formal Description Interaction-ID: 96252 |
drug/chemical compound increases_quantity of gene/protein |
| Drugbank entries | Show/Hide entries for Estradiol |
| Comment | Estradiol has recently been shown to modulate glutamate transmission and AMPA receptor binding in the prefrontal cortex (PFC). Estradiol modulation of AMPA receptors in the rodent PFC appears to selectively involve ERalpha, but not ERbeta, receptors. |
|
Formal Description Interaction-ID: 96254 |
drug/chemical compound affects_activity of |
| Drugbank entries | Show/Hide entries for Estradiol |
| Comment | Estradiol and treatment with an ERalpha agonist decreased GluR2 mRNA levels in the rodent PFC, while treatment with an ERbeta agonist had no effect, and oddly neither did OVX. This estradiol modulation of AMPA receptor binding via the GluR2 subunit, which in turn modulates Ca2+ permeability, may be one mechanism by which estradiol exerts its neuroprotective effects. |
|
Formal Description Interaction-ID: 96255 |
|
| Drugbank entries | Show/Hide entries for Estradiol or GRIA2 |
| Comment | During puberty, IGF-I receptor signaling in the PFC becomes more sensitive to estrogen regulation. |
|
Formal Description Interaction-ID: 96256 |
affects_activity of tissue/cell line |
| Comment | In one positron emission tomography (PET) study in elderly human subjects, subjects with high IGF-1 levels had shorter reaction times and showed increased regional signal in the left DLPFC during a working memory task. Thus, prefrontal cortex exposure to estrogen during puberty may be critical to the development of pathways used in executive functioning in later life. |
|
Formal Description Interaction-ID: 96257 |
phenotype increased IGF1 level cooccurs with phenotype decreased reaction times |
| Comment | Estrogen treatment has been shown to reverse both the decreases in PFC dendritic spine density and number as well as the impairments in PFC dependent functions caused by OVX in both rodents and nonhuman primates. |
|
Formal Description Interaction-ID: 96258 |
drug/chemical compound Estrogen increases_activity of cellular component dendritic spine density |
| Comment | One study found that the decrease in spine density in the medial PFC following OVX was accompanied by a decline in performance on object recognition and object placement memory tasks. |
|
Formal Description Interaction-ID: 96261 |
environment ovariectomy decreases_activity of cellular component dendritic spine density |
| Comment | Estradiol differentially affects prefrontal region morphology during pubertal maturation. |
|
Formal Description Interaction-ID: 96262 |
drug/chemical compound affects_activity of tissue/cell line |
| Drugbank entries | Show/Hide entries for Estradiol |
| Comment | Estradiol treatment decreased anxious behaviors in stressed, OVX rats. |
|
Formal Description Interaction-ID: 96265 |
drug/chemical compound decreases_activity of phenotype |
| Drugbank entries | Show/Hide entries for Estradiol |
| Comment | Increases in c-Fos expression have been associated with improvements in memory consolidation in rodent models deficient in its expression. |
|
Formal Description Interaction-ID: 96267 |
phenotype increased Fos expression increases_activity of process memory consolidation |
| Comment | Women with shorter lengths of time between menopause and initiation of estrogen therapy showed a greater positive change in performance on neuropsychological tests measuring executive function than women who started ET at a later time. |
|
Formal Description Interaction-ID: 96269 |
environment short gap time from menopause to first use of hormone replacement therapy increases_activity of phenotype improved executive functioning |
| Comment | Estrogen therapy (ET) and hormone therapy (HT) were shown to protect against age related grey matter degradation in the prefrontal cortex. |
|
Formal Description Interaction-ID: 96270 |
environment hormone replacement therapy decreases_activity of phenotype age related grey matter degradation |
| Comment | Postmenopausal women receiving estrogen plus progesterone exhibited lower cerebral metabolism in the right inferior frontal gyrus than women receiving estrogen alone. Findings in rodents concur with human subject studies indicating that the CNS effects of estrogen alone can be different from those when estrogen is combined with progesterone. |
|
Formal Description Interaction-ID: 96283 |
drug/chemical compound affects_activity of drug/chemical compound Estrogen |
| Drugbank entries | Show/Hide entries for Progesterone |
| Comment | Optimal executive functioning and prefrontal cortex regulation of subcortical brain structures are dependent upon prefrontal concentrations of catecholamines, specifically dopamine (DA) and norepinephrine (NE). |
|
Formal Description Interaction-ID: 96297 |
drug/chemical compound affects_activity of tissue/cell line |
| Comment | Serotonin (5-HT) and acetylcholine (ACh) are also important in prefrontal cortex neurochemical modulation of attention. |
|
Formal Description Interaction-ID: 96298 |
drug/chemical compound affects_activity of tissue/cell line |
| Drugbank entries | Show/Hide entries for Acetylcholine |
| Comment | Dopamine (DA) and norepinephrine (NE), the catecholamines crucial for executive functioning, are modulated by estrogen in the prefrontal cortex. |
|
Formal Description Interaction-ID: 96299 |
drug/chemical compound Estrogen affects_activity of drug/chemical compound |
| Comment | Treatment with 17beta-estradiol both improved memory consolidation and affected dopaminergic, noradrenergic, and serotonergic neurotransmission in the rodent prefrontal cortex. |
|
Formal Description Interaction-ID: 96302 |
drug/chemical compound increases_activity of |
| Drugbank entries | Show/Hide entries for Estradiol |
| Comment | Treatment with 17beta-estradiol both improved memory consolidation and affected dopaminergic, noradrenergic, and serotonergic neurotransmission in the rodent prefrontal cortex. |
|
Formal Description Interaction-ID: 96306 |
drug/chemical compound increases_activity of |
| Drugbank entries | Show/Hide entries for Estradiol |
| Comment | Treatment with 17beta-estradiol both improved memory consolidation and affected dopaminergic, noradrenergic, and serotonergic neurotransmission in the rodent prefrontal cortex. |
|
Formal Description Interaction-ID: 96307 |
drug/chemical compound increases_activity of |
| Drugbank entries | Show/Hide entries for Estradiol |
| Comment | Estrogen significantly raised concentrations of 5-HT, MHPG (3-Methoxy-4-Hydroxyphenylglycol, metabolite of NE), and DOPAC (3-4-dihydroxyphenylalanine, metabolite of DA) in the prefrontal cortex of rats OVXed at 55 to 60 days as well as the turnover rate of NE to MHPG shortly after treatment. |
|
Formal Description Interaction-ID: 96337 |
drug/chemical compound Estrogen increases_quantity of drug/chemical compound 3-Methoxy-4-Hydroxyphenylglycol |
| Comment | Estrogen significantly raised concentrations of 5-HT, MHPG (3-Methoxy-4-Hydroxyphenylglycol, metabolite of NE), and DOPAC (3-4-dihydroxyphenylalanine, metabolite of DA) in the prefrontal cortex of rats OVXed at 55 to 60 days as well as the turnover rate of NE to MHPG shortly after treatment. |
|
Formal Description Interaction-ID: 96338 |
drug/chemical compound Estrogen increases_quantity of drug/chemical compound 3-4-dihydroxyphenylalanine |
| Comment | Estrogen significantly raised concentrations of 5-HT, MHPG (3-Methoxy-4-Hydroxyphenylglycol, metabolite of NE), and DOPAC (3-4-dihydroxyphenylalanine, metabolite of DA) in the prefrontal cortex of rats OVXed at 55 to 60 days as well as the turnover rate of NE to MHPG shortly after treatment. |
|
Formal Description Interaction-ID: 96339 |
drug/chemical compound Estrogen decreases_quantity of drug/chemical compound |
| Comment | Treatment with significantly higher or lower doses of 17beta-estradiol or higher doses of 17alpha-estradiol were found to be ineffective in improving spatial and non-spatial memory consolidation in OVX rats despite the increase in neurotransmitter levels that occurred at the higher doses, indicating that estrogen’s beneficial effects on cognition are dose dependent. |
|
Formal Description Interaction-ID: 96340 |
drug/chemical compound NOT affects_activity of process memory consolidation |
| Comment | Treatment with significantly higher or lower doses of 17beta-estradiol or higher doses of 17alpha-estradiol were found to be ineffective in improving spatial and non-spatial memory consolidation in OVX rats despite the increase in neurotransmitter levels that occurred at the higher doses, indicating that estrogen’s beneficial effects on cognition are dose dependent. |
|
Formal Description Interaction-ID: 96341 |
phenotype increased estradiol level increases_quantity of drug/chemical compound neurotransmitter |
| Comment | Treatment with significantly higher or lower doses of 17beta-estradiol or higher doses of 17alpha-estradiol were found to be ineffective in improving spatial and non-spatial memory consolidation in OVX rats despite the increase in neurotransmitter levels that occurred at the higher doses, indicating that estrogen’s beneficial effects on cognition are dose dependent. |
|
Formal Description Interaction-ID: 96342 |
drug/chemical compound affects_activity of |
| Drugbank entries | Show/Hide entries for Estradiol |
| Comment | Treatment with significantly higher or lower doses of 17beta-estradiol or higher doses of 17alpha-estradiol were found to be ineffective in improving spatial and non-spatial memory consolidation in OVX rats despite the increase in neurotransmitter levels that occurred at the higher doses, indicating that estrogen’s beneficial effects on cognition are dose dependent. |
|
Formal Description Interaction-ID: 96343 |
drug/chemical compound affects_activity of |
| Comment | OVX elevated catechol-o-methyl transferase (COMT), an enzyme involved in DA metabolism, protein expression and enzyme activity in the PFC of female rats, as did treatment with tamoxifen, an estrogen antagonist. |
|
Formal Description Interaction-ID: 96344 |
environment ovariectomy increases_quantity of gene/protein |
| Drugbank entries | Show/Hide entries for COMT |
| Comment | OVX elevated catechol-o-methyl transferase (COMT), an enzyme involved in DA metabolism, protein expression and enzyme activity in the PFC of female rats, as did treatment with tamoxifen, an estrogen antagonist. |
|
Formal Description Interaction-ID: 96345 |
gene/protein affects_activity of process |
| Drugbank entries | Show/Hide entries for COMT |
| Comment | OVX elevated catechol-o-methyl transferase (COMT), an enzyme involved in DA metabolism, protein expression and enzyme activity in the PFC of female rats, as did treatment with tamoxifen, an estrogen antagonist. |
|
Formal Description Interaction-ID: 96346 |
drug/chemical compound decreases_activity of drug/chemical compound Estrogen |
| Drugbank entries | Show/Hide entries for Tamoxifen |
| Comment | Decreases in COMT (o-methyl transferase) protein expression and enzyme activity were observed in male rats receiving estrogen, suggesting sex differences in the effects of estrogen on dopamine metabolism. |
|
Formal Description Interaction-ID: 96347 |
phenotype sex, male decreases_activity of gene/protein |
| Drugbank entries | Show/Hide entries for COMT |
| Comment | Estradiol treatment initiated 5 months after OVX increased choline acetyltransferase (ChAT) protein levels in the PFC while the same treatment administered immediately following OVX did not, leading the authors to suggest that the period of hormone deprivation sensitized PFC cholinergic systems to the effects of estrogen (delay in prefrontal cortex sensitization). |
|
Formal Description Interaction-ID: 96354 |
drug/chemical compound NOT affects_quantity of gene/protein |
| Drugbank entries | Show/Hide entries for Estradiol |
| Comment | Estradiol has recently been shown to modulate glutamate transmission and AMPA receptor binding in the prefrontal cortex (PFC). Estradiol modulation of AMPA receptors in the rodent PFC appears to selectively involve ERalpha, but not ERbeta, receptors. |
|
Formal Description Interaction-ID: 96355 |
drug/chemical compound affects_activity of process AMPA receptor complex binding |
| Drugbank entries | Show/Hide entries for Estradiol |
| Comment | During puberty, IGF-I receptor signaling in the PFC becomes more sensitive to estrogen regulation. |
|
Formal Description Interaction-ID: 96356 |
increases_activity of process IGF1R signaling pathway |
| Comment | Estradiol and treatment with an ERalpha agonist decreased GluR2 mRNA levels in the rodent PFC, while treatment with an ERbeta agonist had no effect, and oddly neither did OVX. This estradiol modulation of AMPA receptor binding via the GluR2 subunit, which in turn modulates Ca2+ permeability, may be one mechanism by which estradiol exerts its neuroprotective effects. |
|
Formal Description Interaction-ID: 96358 |
gene/protein affects_activity of process Calcium permeability |
| Drugbank entries | Show/Hide entries for GRIA2 |
| Comment | During puberty, IGF-I receptor signaling in the PFC becomes more sensitive to estrogen regulation. |
|
Formal Description Interaction-ID: 96360 |
increases_activity of drug/chemical compound Estrogen |
| Comment | In one positron emission tomography (PET) study in elderly human subjects, subjects with high IGF-1 levels had shorter reaction times and showed increased regional signal in the left DLPFC (in the dorsolateral prefrontal cortex) during a working memory task. Thus, prefrontal cortex exposure to estrogen during puberty may be critical to the development of pathways used in executive functioning in later life. |
|
Formal Description Interaction-ID: 96362 |
phenotype increased IGF1 level cooccurs with phenotype increased regional signal |
| Comment | Estrogen treatment has been shown to reverse both the decreases in PFC dendritic spine density and number as well as the impairments in PFC dependent functions caused by OVX in both rodents and nonhuman primates. |
|
Formal Description Interaction-ID: 96364 |
drug/chemical compound Estrogen increases_activity of tissue/cell line |
| Comment | One study found that the decrease in spine density in the medial PFC following OVX was accompanied by a decline in performance on object recognition and object placement memory tasks. |
|
Formal Description Interaction-ID: 96376 |
phenotype decreased dendritic spine density cooccurs with phenotype decreased object recognition and object placement memory tasks |
| Comment | Estradiol differentially affects prefrontal region morphology during pubertal maturation. |
|
Formal Description Interaction-ID: 96377 |
increases_activity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | Postmenopausal women who had used HT had significantly greater prefrontal grey matter volumes than postmenopausal women who had never used HT. |
|
Formal Description Interaction-ID: 96382 |
environment hormone replacement therapy cooccurs with phenotype increased prefrontal grey matter volumes |
| Comment | Postmenopausal women receiving estrogen plus progesterone exhibited lower cerebral metabolism in the right inferior frontal gyrus than women receiving estrogen alone. Findings in rodents concur with human subject studies indicating that the CNS effects of estrogen alone can be different from those when estrogen is combined with progesterone. |
|
Formal Description Interaction-ID: 96383 |
drug/chemical compound decreases_activity of process cerebral metabolism |
| Drugbank entries | Show/Hide entries for Progesterone |
| Comment | Postmenopausal women receiving estrogen plus progesterone exhibited lower cerebral metabolism in the right inferior frontal gyrus than women receiving estrogen alone. Findings in rodents concur with human subject studies indicating that the CNS effects of estrogen alone can be different from those when estrogen is combined with progesterone. |
|
Formal Description Interaction-ID: 96384 |
drug/chemical compound Estrogen decreases_activity of process cerebral metabolism |