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Curr Biol. 2017 Dec 18;27(24):3859-3863.e3. doi: 10.1016/j.cub.2017.10.071. Epub 2017 Nov 30.

Maternal Brain TNF-α Programs Innate Fear in the Offspring.

Author information

1
Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA; Psychological Science Department, Vassar College, 124 Raymond Avenue, Poughkeepsie, NY 12604, USA.
2
Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA.
3
Department of Pharmacology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA. Electronic address: mtoth@med.cornell.edu.

Abstract

Tumor necrosis factor alpha (TNF-α) is a cytokine that not only coordinates local and systemic immune responses [1, 2] but also regulates neuronal functions. Most prominently, glia-derived TNF-α has been shown to regulate homeostatic synaptic scaling [3-6], but TNF-α-null mice exhibited no apparent cognitive or emotional abnormalities. Instead, we found a TNF-α-dependent intergenerational effect, as mothers with a deficit in TNF-α programmed their offspring to exhibit low innate fear. Cross-fostering and conditional knockout experiments indicated that a TNF-α deficit in the maternal brain, rather than in the hematopoietic system, and during gestation was responsible for the low-fear offspring phenotype. The level of innate fear governs the balance between exploration/foraging and avoidance of predators and is thus fundamentally important in adaptation, fitness, and survival [7]. Because maternal exercise and activity are known to reduce both brain TNF-α [8] and offspring innate fear [9], whereas maternal stress has been reported to increase brain TNF-α [10] and offspring fear and anxiety [11, 12], maternal brain TNF-α may report environmental conditions to promote offspring behavioral adaptation to their anticipated postnatal environment.

KEYWORDS:

TNF; anxiety; behavioral adaptation; conditional knockout; cross-fostering; evolution; fear; maternal effect; maternal programming

PMID:
29199072
PMCID:
PMC6170164
DOI:
10.1016/j.cub.2017.10.071
[Indexed for MEDLINE]
Free PMC Article

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