CA3 / UT MD Anderson Cancer Center - LARVOL DELTA

Microglia-Mediated Synaptic Dysfunction Contributes to Chemotherapy-Related Cognitive Impairment. (PubMed, J Neurochem) - "Adult male mice were treated with the chemotherapeutic drugs 5-fluorouracil and leucovorin (5-Fu/LV, intraperitoneal injection, I.P.) on Days 1, 8, and 15 at a dosage of 50 mg/kg for 5-Fu and 90 mg/kg for LV for 3 weeks...Furthermore, 5-Fu/LV treatment reduced the long-term potentiation (LTP) recorded in the hippocampal CA1 region in response to a theta burst stimulation of the CA3-CA1 pathway and decreased the evoked N-methyl-D-aspartic acid receptor (NMDAR)-excitatory postsynaptic currents (NMDAR-EPSCs) in CA1 neurons. Cotreatment with the microglial inhibitor minocycline (33 mg/kg, daily for 3 weeks) restored cognitive deficits and microglial ramification, decreased the number of CD68-positive microglia, and reversed the reductions in LTP and the amplitude of NMDAR-EPSCs in 5-Fu/LV-treated mice. Our data suggest that microglial dysfunction and related synaptic dysfunction contribute to 5-Fu/LV-induced cognitive impairment."

Journal • Alzheimer's Disease • Cognitive Disorders • Oncology • CA3 • CD68

Age-related decline in hippocampal tyrosine phosphatase PTPRO is a mechanistic factor in chemotherapy-related cognitive impairment. (PubMed, JCI Insight) - "To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro-/- female mice with doxorubicin (DOX) because Ptpro-/- female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration...On the other hand, restoration of PTPRO in the hippocampal CA3 region significantly ameliorate CRCI in Ptpro-/- female mice...Mechanistically, BBR upregulates PTPRO by downregulating miR-25-3p, which directly targeted PTPRO. These findings collectively demonstrate the protective role of hippocampal PTPRO against CRCI."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Oncology • EPHA4 • MIR25