The neurotoxic effect of lactational PFOS exposure on cerebellar functional development in male mice

Neurotransmission Targets of Per- and Polyfluoroalkyl Substance Neurotoxicity: Mechanisms and Potential Implications for Adverse Neurological Outcomes

“…There is growing evidence that PFOS, PFOA, and PFAS mixtures lead to changes in neurotransmitter levels, ,− alter neurotransmitter receptor and transporter expression and function, ,,,,,− and change neurotransmitter metabolism. ,− ,,,,,,,,,, Although the major focus for the evaluation of PFAS neurotoxicity has been on PFAS developmental neurotoxicity, ,,,− ,− ,,,,,,,,− PFAS exposure during both development and adulthood may change neurotransmitter levels in a brain region-specific manner (Table ). Lifelong exposure of humans to PFAS may result in dynamic changes in neurological function resulting from PFAS accumulation over time.…”

“…The voltage-gated and glutamate receptor activated calcium channels expressed in the brain, including if they have been assessed for PFAS toxicity, are summarized in Table . Although many different types of voltage-gated calcium channels are expressed in the brain, only the L-type calcium channels have been demonstrated to have currents affected by PFAS in the studies that were discussed above. , As outlined in Table , many of the neurological functions associated with L-type channels including learning and memory (subtype 1.2), striatal dopaminergic motor function (subtype 1.3), and psychiatric mental health (subtypes 1.2 and 1.3) have been demonstrated to be negatively affected by PFAS exposure. , Currently, the NMDA and AMPA glutamate receptors are the best characterized calcium transporters to be affected by PFAS, followed by the L-type voltage-gated calcium channels.…”

“…The most reproduced functional deficits resulting from PFAS exposure are the effects that PFOS and PFOA have on motor function ,,,− and learning and memory. ,, Additionally, there is some mechanistic and functional laboratory evidence that may explain the controversial association between attention-deficit/hyperactivity disorder (ADHD) and PFAS exposure. ,,− This section aims to relate the alteration of neurotransmission to functional deficits and human disease with mechanistic evidence.…”

“…The evidence of PFAS exposure’s persistent and transient changes in the dopaminergic and cholinergic systems, respectively, can potentially inform the neurotransmitter systems that are likely responsible for PFAS-induced motor behavioral changes. ,,,, Hallgren et al demonstrated that mice with a single developmental exposure to PFOS had persistent deficits to acclimation in the open-field locomotor experiment. The deficit to acclimation was apparent by the PFOS-treated mice having hypoactivity in the first 20 min and hyperactivity in the last 20 min of 1 h in the activity chamber, when compared to the control animals .…”

“…Ongoing research has identified that the PFAS’s neurotoxic targets for neurotransmission alter neurotransmitter levels, ,− synaptic protein expression and function, ,,,,,− and calcium signaling. − ,,− This Review aims to critically analyze the state of PFAS neurotoxicity with focus on neurotransmission-related end points and to reveal PFAS’s potential targets of neurological disease that require epidemiological evaluation in the future. Recent reviews have broadly focused on brain accumulation and neurotoxicity. ,,− This critical analysis of the field focuses specifically on neurotransmission targets, which may underlie adverse neurological outcomes.…”