Transgenerational effects of early life stress on the fecal microbiota in mice.

Stress in early life can affect the progeny and increase the risk to develop psychiatric and cardiometabolic diseases across generations. The cross-generational effects of early life stress have been modeled in mice and demonstrated to be associated with epigenetic factors in the germline. While stress is known to affect gut microbial features, whether its effects can persist across life and be passed to the progeny is not well defined. Here we show that early postnatal stress in mice shifts the fecal microbial composition (binary Jaccard index) throughout life, including abundance of eight amplicon sequencing variants (ASVs). Further effects on fecal microbial composition, structure (weighted Jaccard index), and abundance of 16 ASVs are detected in the progeny across two generations. These effects are not accompanied by changes in bacterial metabolites in any generation. These results suggest that changes in the fecal microbial community induced by early life traumatic stress can be perpetuated from exposed parent to the offspring.

Symposium summary: epigenetic inheritance-impact for biology and society 23-25 August 2023, Zürich, Switzerland.

The possibility that acquired traits can be transmitted across generations has been the subject of intense research in the past decades. This biological process is of major interest to many scientists and has profound implications for biology and society but has complex mechanisms and is therefore challenging to study. Because it involves factors independent from the DNA sequence, this form of heredity is classically referred to as epigenetic inheritance. Many studies have examined how life experiences and various environmental factors can cause phenotypes that are heritable and be manifested in subsequent generations. Recognizing the major importance and complexity of this research, the fourth edition of the Epigenetic Inheritance Symposium Zürich brought together experts from diverse disciplines to address current questions in the field of epigenetic inheritance and present recent findings. The symposium had sessions dedicated to epidemiological evidence and animal models, transmission mechanisms, methodologies and the far-reaching impact on society and evolution. This report summarizes the talks of speakers and describes additional activities offered during the symposium including poster sessions and an art competition on the topic of epigenetic inheritance.

Ventral midline thalamus lesion prevents persistence of new (learning-triggered) hippocampal spines, delayed neocortical spinogenesis, and spatial memory durability.

The ventral midline thalamus contributes to hippocampo-cortical interactions supporting systems-level consolidation of memories. Recent hippocampus-dependent memories rely on hippocampal connectivity remodeling. Remote memories are underpinned by neocortical connectivity remodeling. After a ventral midline thalamus lesion, recent spatial memories are formed normally but do not last. Why these memories do not endure after the lesion is unknown. We hypothesized that a lesion could interfere with hippocampal and/or neocortical connectivity remodeling. To test this hypothesis, in a first experiment male rats were subjected to lesion of the reuniens and rhomboid (ReRh) nuclei, trained in a water maze, and tested in a probe trial 5 or 25 days post-acquisition. Dendritic spines were counted in the dorsal hippocampus and medial prefrontal cortex. Spatial learning resulted in a significant increase of mushroom spines in region CA1. This modification persisted between 5 and 25 days post-acquisition in Sham rats, not in rats with ReRh lesion. Furthermore, 25 days after acquisition, the number of mushroom spines in the anterior cingulate cortex (ACC) had undergone a dramatic increase in Sham rats; ReRh lesion prevented this gain. In a second experiment, the increase of c-Fos expression in CA1 accompanying memory retrieval was not affected by the lesion, be it for recent or remote memory. However, in the ACC, the lesion had reduced the retrieval-triggered c-Fos expression observed 25 days post-acquisition. These observations suggest that a ReRh lesion might disrupt spatial remote memory formation by preventing persistence of early remodeled hippocampal connectivity, and spinogenesis in the ACC.