» Articles » PMID: 33352471

17β-estradiol Activation of Dorsal Hippocampal TrkB is Independent of Increased Mature BDNF Expression and is Required for Enhanced Memory Consolidation in Female Mice

Overview
Date 2020 Dec 22
PMID 33352471
Citations 10
Authors
Affiliations
Soon will be listed here.
Abstract

The potent estrogen 17β-estradiol (E) is known to enhance hippocampal memory and plasticity, however the molecular mechanisms underlying these effects remain unclear. Brain derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB) are regulated by E, but the potential mechanistic roles of neurotrophic signaling in E-induced enhancement of memory are not well understood. Here, we examined the effects of hippocampal TrkB signaling on E-induced enhancement of memory consolidation in the object placement and recognition tasks. Bilateral infusion of the TrkB antagonist ANA-12 into the dorsal hippocampus of ovariectomized female mice blocked E-induced enhancement of memory consolidation, supporting a role for TrkB-mediated signaling in estrogenic regulation of memory. Although dorsal hippocampal E infusion increased levels of phospho-TrkB and mature BDNF (mBDNF) in the dorsal hippocampus within 4-6 h, E-induced increases in hippocampal mBDNF expression were not required for hippocampal TrkB activation and were not inhibited by TrkB antagonism. Thus, E regulates TrkB signaling to facilitate memory consolidation in a manner independent of mBDNF expression. Together these results provide the first direct evidence that E modulation of hippocampal TrkB signaling is required for its beneficial effects on memory consolidation and provide additional characterization of the ways in which TrkB/BDNF signaling is regulated by E in the hippocampus.

Citing Articles

The novel estrogen receptor beta agonist EGX358 and genotype influence memory, vasomotor, and anxiety outcomes in an Alzheimer's mouse model.

Schwabe M, Fleischer A, Kuehn R, Chaudhury S, York J, Sem D Front Aging Neurosci. 2024; 16:1477045.

PMID: 39629477 PMC: 11613887. DOI: 10.3389/fnagi.2024.1477045.


TrkB-mediated sustained neuroprotection is sex-specific and Erα-dependent in adult mice following neonatal hypoxia ischemia.

Chanana V, Hackett M, Deveci N, Aycan N, Ozaydin B, Cagatay N Biol Sex Differ. 2024; 15(1):1.

PMID: 38178264 PMC: 10765746. DOI: 10.1186/s13293-023-00573-0.


The causal involvement of the BDNF-TrkB pathway in dentate gyrus in early-life stress-induced cognitive deficits in male mice.

Sun Y, Su Y, Wang Q, Zheng J, Zhang C, Wang T Transl Psychiatry. 2023; 13(1):173.

PMID: 37225683 PMC: 10209152. DOI: 10.1038/s41398-023-02476-5.


APOE4 homozygote females are resistant to the beneficial effects of 17β-estradiol on memory and CA1 dendritic spine density in the EFAD mouse model of Alzheimer's disease.

Taxier L, Philippi S, Fleischer A, York J, LaDu M, Frick K Neurobiol Aging. 2022; 118:13-24.

PMID: 35843109 PMC: 10756028. DOI: 10.1016/j.neurobiolaging.2022.06.005.


Extracellular matrix metalloproteinase-9 (MMP-9) is required in female mice for 17β-estradiol enhancement of hippocampal memory consolidation.

Gross K, Lincoln C, Anderson M, Geiger G, Frick K Psychoneuroendocrinology. 2022; 141:105773.

PMID: 35490640 PMC: 9173600. DOI: 10.1016/j.psyneuen.2022.105773.


References
1.
Kim J, Szinte J, Boulware M, Frick K . 17β-Estradiol and Agonism of G-protein-Coupled Estrogen Receptor Enhance Hippocampal Memory via Different Cell-Signaling Mechanisms. J Neurosci. 2016; 36(11):3309-21. PMC: 4792941. DOI: 10.1523/JNEUROSCI.0257-15.2016. View

2.
Solum D, Handa R . Estrogen regulates the development of brain-derived neurotrophic factor mRNA and protein in the rat hippocampus. J Neurosci. 2002; 22(7):2650-9. PMC: 6758321. DOI: 20026251. View

3.
Spencer-Segal J, Waters E, Bath K, Chao M, McEwen B, Milner T . Distribution of phosphorylated TrkB receptor in the mouse hippocampal formation depends on sex and estrous cycle stage. J Neurosci. 2011; 31(18):6780-90. PMC: 3108038. DOI: 10.1523/JNEUROSCI.0910-11.2011. View

4.
Bekinschtein P, Cammarota M, Igaz L, Bevilaqua L, Izquierdo I, Medina J . Persistence of long-term memory storage requires a late protein synthesis- and BDNF- dependent phase in the hippocampus. Neuron. 2007; 53(2):261-77. DOI: 10.1016/j.neuron.2006.11.025. View

5.
Bi R, Broutman G, Foy M, Thompson R, Baudry M . The tyrosine kinase and mitogen-activated protein kinase pathways mediate multiple effects of estrogen in hippocampus. Proc Natl Acad Sci U S A. 2000; 97(7):3602-7. PMC: 16286. DOI: 10.1073/pnas.97.7.3602. View