Table 1.
List of studies addressing the effects of estrogen in different models.
| Experimental Model | Preparation | E2 Effects | Receptor Involved | Reference |
|---|---|---|---|---|
| Ovariectomized mice | Whole brain mitochondria | ↑ activity of complex IV (COX); ↑ expression of nuDNA subunit COX IV, mtDNA subunit COX I, and of the antioxidant enzymes MnSOD, PrdxV, and glutathione peroxidase; ↓ lipoperoxidation; ↑ maximal mitochondrial capacity | ERα or Erβ | Irwin et al., 2012 [115] |
| Human lens cells | Cell culture | ↓ oxidative stress; ↓ mitochondrial membrane permeability | ERβ1 | Flynn et al., 2008 [116] |
| Human pituitary tumor cells | Cell culture | ↑ expression of the COX II subunit | N.I. | Van Itallie et al., 1988 [117] |
| Rats | Hippocampal tissue | ↑ expression of the COX III subunit; ↑ activity of COX | N.I. | Bettini et al., 1992 [118] |
| Several human cell lines | Cell culture | ↑ expression of the COX VII subunit | N.I. | Watanabe et al., 1998 [119] |
| Mouse cortical and mesencephalic astrocytes | Cell culture | ↑ expression of catalytic subunits of the ETC complexes I, III, IV and V; ↑ activity of ATP synthase; ↑ mtDNA/nuDNA ratio | N.I. | Araújo et al., 2008 [120] |
| MCF-7 and H1793 cells | Cell culture | ↑ expression of NRF-1; ↑ mitochondrial biogenesis | N.I. | Mattingly et al., 2008 [121] |
| Mouse astrocytes | Cell culture | ↑ transcription of mitochondrial fusion/fission proteins | N.I. | Arnold et al., 2008 [123] |
| HeLa cells | Cell culture | ↑ MCU-mediated mitochondrial Ca2+ uptake | N.I. | Lobatón et al., 2005 [124] |
| Ischemia-perfusion in Female rats | Brain tissue | ↑ expression of anti-apoptotic proteins (e.g., Bcl-2) | Erα | Zhang et al., 2017 [125] |
| SH-SY5Y cells | Cell culture | ↑ expression of the antioxidant proteins thioredoxin and MnSOD | N.I. | Chiueh et al., 2003 [126] |
| HT22 cells, mouse hippocampal and neocortical, and C6 cells | Cell culture | ↑ expression of glutathione | N.I. | Schmidt et al., 2002 [127] |
| Rat cortical neurons submitted to glutamatergic excitotoxicity | Cell culture | ↓ apoptosis; prevention of cytochrome c release; ↓ expression of caspase-3 | N.I. | Zhang et al., 2005 [128] |
| Pubertal period female mice | Ventromedial hypothalamus | ↑ microglial response to LPS | N.I. | Velez-Perez et al., 2020 [185] |
| Rat cortical neurons transfected with mutated DISC1 | Cell culture | ↑ spine density and synaptic proteins; ↓ DISC1 aggregates | N.I. | Erli et al., 2020 [244] |
| Rat cortical neurons submitted to glutamatergic excitotoxicity | Cell culture | ↓ release of lactate dehydrogenase | Classical estrogen receptors | Singer et al., 1996 [281] |
| Ovariectomized rats | Hypothalamic arcuate nucleus | ↑ number of Bcl-2-immunoreactive neurons | N.I. | Garcia-Segura et al., 1998 [282] |
| Rat hippocampal neurons submitted to oxidative stress inducers | Cell and organotypic culture | Prevention of peroxide accumulation | Independent on any ER activation | Behl et al., 1997 [283] |
| Ovariectomized rats | Several brain regions | Prevention of serotonin-receptor loss due to ovariectomy | N.I. | Cyr et al., 2000 [284] |
| Ovariectomized rats | CA1-region hippocampal neurons | ↑ excitability, independent of NMDA receptors | N.I. | Wong et al., 1992 [254] |
| Male adult rats | Hippocampal slices | ↑ synaptic responses by a mechanism dependent on integrin activation and signaling | Erβ | Wang et al., 2016 [257] |
| Rats and mice | Cell culture and brain slices | ↓ amplitude of inhibitory synaptic currents; destabilization of GABAARs and gephyrin at inhibitory synapses | N.I. | Mukherjee et al., 2017 [285] |
| Rats | Frontal cortex organotypic slice cultures | ↑ cortical expression of parvalbumin in both deep and superficial layers | N.I. | Ross and Porter, 2002 [263] |
| Ovariectomized monkeys | Dorsolateral prefrontal cortex | Regulated 40 genes, including ↑ expression of C-FOS and ↓ expression of E2F1 and TFIIB mRNA and protein | N.I. | Wang et al., 2004 [270] |
| Ovariectomized rats | Frontal cortex | Regulated 16 genes including ↓ expression of complement C3 and C4b, Ccl2, Tgfb1, macrophage expressed gene Mpeg1, RT1-Aw2, Cx3cr1, Fcgr2b, Cd11b, Tlr4 and Tlr9, defensin Np4, RatNP-3b, IgG-2a, Il6 and the ER gene Esr1 | ERα and Erβ | Sárvári et al., 2011 [271] |
| Ovariectomized mice | Hippocampus | Regulated 187 genes, mostly of them involved in transcription, cell signaling, cell growth, and lipid and protein metabolism | N.I. | Aenlle et al., 2009 [275] |
| Female mice | Dorsal hippocampus | Alteration in the expression of 204 genes, of which 23 are involved with learning/memory; changes in the content of the proteins Hsp70, Igfbp2, Actn4, Tubb2a, and Snap25 | N.I. | Pechenino and Frick, 2009 [276] |
| Human fetus | Neuron and glial cell cultures | Altered expression of 199 genes, many implicated in cell differentiation, cell cycle regulation, signal transduction, apoptosis, and ion channels and transporters | N.I. | Csöregh et al., 2009 [277] |
| Gonadectomized male rats | Hippocampus | ↑ levels of BDNF mRNA and protein | Erα | Solum and Handa, 2002 [278] |
| Intact and ovariectomized female rats | Hippocampus, cortex and spinal cord | ↑ expression of the BDNF gene | N.I. | Allen and McCarson, 2005 [279] |
| Ovariectomized rats | Amygdala, hypothalamus, nucleus accumbens, midbrain, and ventral tegmental area | ↑ levels of dopamine and serotonin receptors mRNA; ↓ levels of ERα and ERβ mRNA | N.I. | Zhou et al., 2002 [280] |
| Human cells | iPSC-derived forebrain neurons | ↑ number of dendritic branches | N.I. | Shum et al., 2015 [286] |
| Human cells in a rat model of Parkinson’s disease | iPSC-derived dopaminergic neurons | Activation of integrin α5β1 in the rat striatum; ↑ integration of grafted neurons into host striatum | N.I. | Nishimura et al., 2016 [287] |
↑, increased; ↓, decreased; ETC, electron transport chain; BDNF, brain-derived neurotrophic factor; iPSC, induced pluripotent stem cell; LPS, lipopolysaccharide; MCU, mitochondrial calcium uniporter; N.I., not informed in the study; NMDA, N-methyl-D-aspartate.