# Estradiol Regulation of Hypothalamic Astrocyte Glycogen

> **NIH NIH R01** · UNIVERSITY OF LOUISIANA AT MONROE · 2020 · $352,726

## Abstract

Abstract:
Glycogen is a critical reserve of oxidizable fuel for brain neuron use during states of heightened activity or
glucoprivation. Iatrogenic hypoglycemia is a recurring complication of obligatory meticulous control of
insulin-dependent diabetes mellitus and poses a serious risk of neural injury. There is thus keen interest
to maximize protection against harmful effects of hypoglycemia by cerebral glycogen. Our studies show
that estradiol and hindbrain catecholamine neurotransmitter signals converge to regulate ventromedial
hypothalamus nucleus (VMH) glycogen metabolic enzyme protein expression. This project will address
the hypothesis that astrocyte adenosine 5’-mono-phosphate-activated protein kinase (AMPK) regulates
VMH glycogen metabolism, and that estradiol acts via classical receptor-mediated signaling to control
effects of basal and hypoglycemia-enhanced hindbrain noradrenergic input on sensor activity. Estrogen
augmentation of the glycogen fuel reserve is presumed to correlate with prolonged local nerve cell
energetic stability during hypoglycemia. Proposed research is guided by three Specific Aims: 1)
Determine effects of estradiol on hypothalamic metabolic sensory structure glycogen content in normo-
and hypoglycemic ovariectomized female rats; 2) Assess the role of VMH astrocyte estrogen receptor
variants in AMPK- mediated glycogen metabolic responses to glucoprivation; and 3) Determine substrates
for interaction of hindbrain catecholamine and estrogen regulation of VMH astrocyte glycogen
metabolism. This project will use a combinatory in situ immunocytochemistry/laser-capture
microdissection/high-sensitivity qPCR and Western blot approach for quantitative cell type-specific
molecular profiling; pharmacologic tools for manipulation of glycogen metabolic enzyme activity; nano-
technological devices for selective knockdown of astrocyte protein expression; paired glycogen
densitometric histochemistry and nerve cell AMPK/phosphoAMPK Western blot analyses to correlate
high-resolution quantitative glycogen maps with VMH metabolic sensory nerve cell AMPK activity; and
scanning particle-induced X-ray emission spectrometry to perform single-cell microanalysis of electrolyte
correlates of VMH neuron electrical activity, and to quantify effects of estradiol on hypoglycemic patterns
of transynaptic anterograde transport of Mn, a reliable indicator of neuron activation, between hindbrain
A2 noradrenergic neurons and the VMH. This work will utilize an innovative assembly of investigative
strategies to identify cellular and molecular mechanisms of estrogen regulation of astrocyte glycogen
mass, knowledge that can be leveraged to advance development of therapeutic strategies for neuro-
protective amplification of brain glycogen levels.

## Key facts

- **NIH application ID:** 10004512
- **Project number:** 5R01DK109382-05
- **Recipient organization:** UNIVERSITY OF LOUISIANA AT MONROE
- **Principal Investigator:** KAREN P BRISKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $352,726
- **Award type:** 5
- **Project period:** 2016-09-19 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10004512

## Citation

> US National Institutes of Health, RePORTER application 10004512, Estradiol Regulation of Hypothalamic Astrocyte Glycogen (5R01DK109382-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10004512. Licensed CC0.

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