L-type calcium channel antagonist isradipine age-dependently decreases plaque associated dystrophic neurites in 5XFAD mouse model

Epidemiologthal viudis ctiggest that L- type ca: Run channel tLTCC) antagonists may redu-'e the incidence of ageassociated neurodegenriatiye uiseases inducing Alzheimer s disease (AD). However, the netunprotective mechanism of LTCC antago_fists is u_:known. Amyloid-fi (Ap) pathology disrupts intracellular cakium signaling, which regulates lysosomes and microglial responses. Neurons near Ap plaques develop dystrophic netuites, which are abnormal s Nellings that accumulate tisosomes. Further, microglia accumulate mound Ap plaques and secrete inflammatory cy tokines. We hypothesized that antagonism of LTCCs with isradipine would reduce Ap plaque-associated dystrophic nemites and inflammatory microglia in the SXFAD mouse model by restoring normal intracellular calcium regulation. To test this hypothesis, we treated 6- and 9-month-old 5XFAD mice with isradipine and tested behavior, examined Ap plaques, microglia, and dystrophic netuites. We found that isradipine treatment age-dependently reduces dystrophic netuites and leads to trending decreases in Ap but does not modulate plaque associated microglia regardless of age. Our adings provide insight into how antagonizing LTCCs alters specific cell types in the Ali plaque environment, providing valuable information for potential treatment targets in future AD studies.

Automated summary

Epidemiological studies suggest that L-type calcium channel antagonists may reduce the incidence of age-associated neurodegenerative diseases, including Alzheimer's disease. However, the protective mechanism of LTCC antagonists is unknown.