Lead-induced neurotoxic effects on the synaptic signalling pathways and its association with autism spectrum disorder: a systematic review

Lead is a toxic heavy metal that poses significant health risks, which include neurodevelopmental disorders such as autism spectrum disorder (ASD). This review examines the effects of lead neurotoxicity on synaptic pathways which are relatively unexplored and their potential role in the development of ASD. Lead exposure occurs through various environmental sources, including contaminated water, soil, paint, and industrial appliances. Once absorbed, lead accumulates in soft tissues and bones, causes prolonged neurological damage, especially in children. ASD is characterised by impaired communication, repetitive behaviours, and cognitive challenges, with increasing evidence linking environmental factors like heavy metal exposure to its onset. Synaptic signalling disruption is a key aspect of ASD and lead interferes with the synaptic pathways by inhibiting calcium influx, leading to cognitive impairments and memory issues. This review is an overview of the previously reported findings that explains the role of lead in reducing N-methyl-D-aspartate receptors (NMDAR) function, disrupting the brain-derived neurotrophic factor (BDNF) pathway, and impairing Wnt, GABAergic and dopaminergic signalling pathways. These alterations result in cognitive decline, impaired synaptic plasticity and increased ASD symptoms. Understanding these mechanisms is crucial for developing strategies to mitigate the adverse effects of lead exposure on neurodevelopment.