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Brain Structure and Function

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11.05.2020 | Original Article

Obesity induced by Borna disease virus in rats: key roles of hypothalamic fast-acting neurotransmitters and inflammatory infiltrates

verfasst von: Georg Gosztonyi, Hanns Ludwig, Liv Bode, Moujahed Kao, Manfred Sell, Peter Petrusz, Béla Halász

Erschienen in: Brain Structure and Function | Ausgabe 5/2020

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Abstract

Human obesity epidemic is increasing worldwide with major adverse consequences on health. Among other possible causes, the hypothesis of an infectious contribution is worth it to be considered. Here, we report on an animal model of virus-induced obesity which might help to better understand underlying processes in human obesity. Eighty Wistar rats, between 30 and 60 days of age, were intracerebrally inoculated with Borna disease virus (BDV-1), a neurotropic negative-strand RNA virus infecting an unusually broad host spectrum including humans. Half of the rats developed fatal encephalitis, while the other half, after 3–4 months, continuously gained weight. At tripled weights, rats were sacrificed by trans-cardial fixative perfusion. Neuropathology revealed prevailing inflammatory infiltrates in the median eminence (ME), progressive degeneration of neurons of the paraventricular nucleus, the entorhinal cortex and the amygdala, and a strikingly high-grade involution of the hippocampus with hydrocephalus. Immune histology revealed that major BDV-1 antigens were preferentially present at glutamatergic receptor sites, while GABAergic areas remained free from BDV-1. Virus-induced suppression of the glutamatergic system caused GABAergic predominance. In the hypothalamus, this shifted the energy balance to the anabolic appetite-stimulating side governed by GABA, allowing for excessive fat accumulation in obese rats. Furthermore, inflammatory infiltrates in the ME and ventro-medial arcuate nucleus hindered free access of appetite-suppressing hormones leptin and insulin. The hormone transport system in hypothalamic areas outside the ME became blocked by excessively produced leptin, leading to leptin resistance. The resulting hyperleptinemic milieu combined with suppressed glutamatergic mechanisms was a characteristic feature of the found metabolic pathology. In conclusion, the study provided clear evidence that BDV-1 induced obesity in the rat model is the result of interdependent structural and functional metabolic changes. They can be explained by an immunologically induced hypothalamic microcirculation-defect, combined with a disturbance of neurotransmitter regulatory systems. The proposed mechanism may also have implications for human health. BDV-1 infection has been frequently found in depressive patients. Independently, comorbidity between depression and obesity has been reported, either. Future studies should address the exciting question of whether BDV-1 infection could be a link, whatsoever, between these two conditions.

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Titel: Obesity induced by Borna disease virus in rats: key roles of hypothalamic fast-acting neurotransmitters and inflammatory infiltrates
verfasst von: Georg Gosztonyi
Hanns Ludwig
Liv Bode
Moujahed Kao
Manfred Sell
Peter Petrusz
Béla Halász
Publikationsdatum: 11.05.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Brain Structure and Function / Ausgabe 5/2020
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-020-02063-0

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