Neuro-Germline Signaling in Transgenerational Epigenetic Inheritance of Behaviors: A Multidisciplinary Synthesi

The Mendelian paradigm, centered on DNA sequence transmission, fails to explain heritable non-genetic traits observed across taxa. This review proposes a multidisciplinary framework for transgenerational epigenetic inheritance (TEI) of acquired behaviors, integrating neuroscience, epigenetics, evolutionary biology, medicine, environmental toxicology, epigenomics, and gene editing. Environmental stimuli trigger neuronal activation, releasing signaling molecules (e.g., microRNAs, exosomes) that reprogram germline epigenomes through targeted histone modifications and DNA methylation. These marks, persisting through meiosis and fertilization, modulate offspring gene expression without altering DNA sequences. Supported by studies in Caenorhabditis elegans, rodents, and humans, the model elucidates how learned behaviors, like stress responses, are transmitted across generations, potentially accelerating adaptation. Advances in single-cell epigenomics and CRISPR-based gene editing enhance mechanistic validation and therapeutic potential. The framework predicts testable molecular pathways and offers transformative implications for evolutionary biology, precision medicine, environmental policy, and ethical governance, highlighting how ancestral experiences shape descendant phenotypes.