Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction

Abstract

Synaptic plasticity forms the basis for learning and memory processes, controlled by a finely tuned interaction of neurotransmitters, intracellular signaling pathways and hormonal modulators. Exogenous substances, especially endocrine disrupting chemicals (EDCs), can significantly disrupt these processes. EDCs such as bisphenols, phthalates, pesticides, PCBs/dioxins, heavy metals and flame retardants interfere with hormonal regulatory circuits, receptor systems and epigenetic programs. They alter glutamatergic transmission, disrupt calcium homeostasis, modulate signal transduction pathways and destabilize structural proteins. This results in functional disorders in long-term potentiation and depression, as well as morphological and functional changes in dendritic spines. In addition to functional deficits, EDCs lead to mitochondrial dysfunction, oxidative stress, inflammatory processes and impaired blood–brain barrier (BBB) integrity. These mechanisms manifest themselves in cognitive impairments, behavioral abnormalities and increased susceptibility to neuropsychiatric disorders. Exposure during sensitive developmental phases is particularly critical, as it can be passed on transgenerationally via epigenetic changes. Integrative analysis shows that heterogenous EDCs undermine neural plasticity via convergent molecular mechanisms. They, therefore, pose a significant challenge to public health and prevention. A better understanding of these processes is essential to strengthen regulatory measures and minimize long-term risks to cognitive function and behavior.