Brain-Derived Neurotrophic Factor (BDNF), Estrogen Receptors, and Mossy Cells.
- 1Child & Adolescent Psychiatry, Neuroscience, and Psychiatry and the Neuroscience Institute, New York University Grossman School of Medicine, New York, New York, USA.
- 2Center for Dementia Research, The Nathan Kline Institute for Psychiatric Research, Orangeburg, New York, USA.
Abstract
Dentate gyrus (DG) function depends on the neurotrophin brain-derived neurotrophic factor (BDNF) which shows robust synthesis in the principal cells, the granule cells (GCs). However, BDNF protein is present in the inner molecular layer (IML), where most afferents to GCs are from hilar mossy cells (MCs). Therefore, we asked whether MCs express BDNF mRNA and protein. Using adult mice, we found that MC BDNF mRNA and protein were expressed in the majority of MC somata and few other hilar neurons. Interestingly, IML BDNF was significantly greater in the ventral compared to dorsal DG. Additionally, dorsal IML BDNF was significantly higher in females on proestrous morning, when serum levels of estrogen peak, relative to metestrous morning, when estrogen is lower. Consistent with this observation, ventral MC somata, which project to the dorsal IML, showed more BDNF mRNA on proestrous morning than metestrous morning. Next, we asked if strong IML BDNF protein expression on proestrous morning was due to estrogen action at estrogen receptors (ERs) because estrogen binding to ERs can increase BDNF synthesis. We found that MCs have high expression of all ERs: ERα, ERβ and GPER1 in both sexes. When sexes were pooled, the percent of MCs labeled by ERβ and GPER1 exceeded the percent of MCs expressing ERα. When proestrous females were examined, GPER1-labeled MCs were greater than MCs labeled by ERα. The results demonstrate robust MC somatic expression of BDNF, relatively high ventral IML expression of BDNF, and estrous cycle dependence. The results also highlight robust MC ER expression, especially ERβ and GPER1, making the hilus a previously underestimated site of estrogen and BDNF action.
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BibTeX
@article{criscuolo2026brainderived,
title = {{Brain-Derived Neurotrophic Factor (BDNF), Estrogen Receptors, and Mossy Cells.}},
author = {Chiara Criscuolo and Monarchsinh Rathod and Fang Jie and Helen E Scharfman},
journal = {Hippocampus},
year = {2026},
month = nov,
doi = {10.1002/hipo.70145},
url = {https://europepmc.org/article/MED/42967900},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Brain-Derived Neurotrophic Factor (BDNF), Estrogen Receptors, and Mossy Cells.
AU - Chiara Criscuolo
AU - Monarchsinh Rathod
AU - Fang Jie
AU - Helen E Scharfman
PY - 2026
DA - 2026/11/01
JO - Hippocampus
DO - 10.1002/hipo.70145
UR - https://europepmc.org/article/MED/42967900
AB - Dentate gyrus (DG) function depends on the neurotrophin brain-derived neurotrophic factor (BDNF) which shows robust synthesis in the principal cells, the granule cells (GCs). However, BDNF protein is present in the inner molecular layer (IML), where most afferents to GCs are from hilar mossy cells (MCs). Therefore, we asked whether MCs express BDNF mRNA and protein. Using adult mice, we found that MC BDNF mRNA and protein were expressed in the majority of MC somata and few other hilar neurons. Interestingly, IML BDNF was significantly greater in the ventral compared to dorsal DG. Additionally, dorsal IML BDNF was significantly higher in females on proestrous morning, when serum levels of estrogen peak, relative to metestrous morning, when estrogen is lower. Consistent with this observation, ventral MC somata, which project to the dorsal IML, showed more BDNF mRNA on proestrous morning than metestrous morning. Next, we asked if strong IML BDNF protein expression on proestrous morning was due to estrogen action at estrogen receptors (ERs) because estrogen binding to ERs can increase BDNF synthesis. We found that MCs have high expression of all ERs: ERα, ERβ and GPER1 in both sexes. When sexes were pooled, the percent of MCs labeled by ERβ and GPER1 exceeded the percent of MCs expressing ERα. When proestrous females were examined, GPER1-labeled MCs were greater than MCs labeled by ERα. The results demonstrate robust MC somatic expression of BDNF, relatively high ventral IML expression of BDNF, and estrous cycle dependence. The results also highlight robust MC ER expression, especially ERβ and GPER1, making the hilus a previously underestimated site of estrogen and BDNF action.
SN - 1050-9631
SN - 1098-1063
ER -