PINK1 deficiency with Ca²⁺ changes in the hippocampus exacerbates septic encephalopathy in mice

PTEN-induced putative kinase 1 (PINK1) is a mitochondrial kinase that protects against oxidative stress-induced cellular death. PINK1 deletion, on the other hand, disrupts mitochondrial calcium (Ca²⁺) homeostasis in various brain disorders. This study looked at how PINK1 affects hippocampal intracellular Ca²⁺ changes in mice with septic encephalopathy. Mice were injected intraperitoneally with lipopolysaccharide (LPS, 5 mg/kg) to induce septic encephalopathy; then, fiber photometry was used to record hippocampal Ca²⁺ transients during behavioral tests in freely moving mice. Basal cytoplasmic Ca²⁺ levels were detected under a fluorescent microscope. LPS induced PINK1 expression and neuronal loss in the hippocampus of mice, whereas no difference in neuronal counts was shown between PINK1 knockout LPS mice and WT LPS mice. PINK1 deficiency led to inhibited Ca²⁺ transients and increased intracellular Ca²⁺ levels in the hippocampus of mice, thus, significantly aggravating the cognitive dysfunction in septic mice. An analysis of Parkin and PLC-γ1, downstream effectors of PINK1, showed that they are associated with the effects of PINK1. These results demonstrate that PINK1 deficiency disrupts intracellular Ca²⁺ homeostasis and exacerbates septic encephalopathy. This observation suggests a protective role of PINK1 in septic encephalopathy.