# Maternal brain-TNF as an environmental sensor in programming offspring anxiety

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $211,260

## Abstract

Abstract
The maternal neuro-endocrine system responds to strong environmental stressors and alters,
via glucocorticoids, offspring stress-responsiveness and emotional behavior. Based on our
recent work, we hypothesize that TNF in the brain represents a complementary pathway that
programs offspring emotional behavior, in particular the level of innate fear. “Central (brain)
TNF” is predicted to respond to a range of stressors, from natural and predictable to more
extreme and unpredictable, while the glucocorticoid system primarily responds to more extreme
environmental stress. This novel environmental sensing/programming function of TNF is
independent from its well-known role in coordinating local and systemic immune responses. To
establish central TNF as an “environmental sensor” in adaptive programming of offspring
behavior first we propose to identify the brain cell, whether neuron or glia, that, via TNF
production/release, is responsible for the intergenerational programming of offspring
fear/anxiety. Second, we will causally link environmental changes, such as enriched
environment and stress, to offspring programming, via maternal central TNF. Specifically, we
will test if environment-induced offspring innate fear responses are altered by the genetic up-
and down-regulation of brain TNF in the mother. Overall, we expect that our work will establish
the central TNF system in the mother as one of the factors that determine the life-long innate
fear/anxiety of the offspring and their resilience and vulnerability to psychological stressor and
psychiatric disease.

## Key facts

- **NIH application ID:** 9828787
- **Project number:** 5R21MH118619-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Miklos Toth
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,260
- **Award type:** 5
- **Project period:** 2018-12-01 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828787

## Citation

> US National Institutes of Health, RePORTER application 9828787, Maternal brain-TNF as an environmental sensor in programming offspring anxiety (5R21MH118619-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9828787. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*