Effect of PI3K inhibitor cancer targeted therapy on emotional reactivity and cognitive functions in mice
Coordinator: Hélène Castel (Rouen)
Treatments such as chemotherapy and new targeted therapies can induce side effects on memory, processing speed and attention, symptoms grouped under the term “Chemofog”. Various new targeted therapies including phosphatidylinositol-3-kinase (PI3K) inhibitors are currently being evaluated in clinical trials in cancer patients. Given the major role of PI3K signaling pathways in synaptic plasticity and learning processes, we compared the effects of buparlisib® (BKM120, Novartis), which can cross the blood-brain-barrier (BBB) with those of the BBB-non-permeable CLR457 (Novartis), two PI3K inhibitors, on memory and exploration behaviors as well as anxious, depressive, compulsive and impulsive behaviors in mice.
Given the major role of PI3K signaling pathways in synaptic plasticity and learning processes, we compare the effects of buparlisib® (BKM120) with the BBB-non permeable CLR457, on memory and exploration behaviors as well as anxious, depressive, compulsive and impulsive behaviors in mice.
Buparlisib and CLR457 and their respective adjuvant were administered orally for 2 weeks in adult male C57B1/6J Rj mice. Plus maze was used to assess the anxious behavior, and tail suspension (TST) and forced swimming (FST) tests were used to assess depressive behaviors. The Morris water maze and object recognition tests were conducted to evaluate memory performances. Early studies of behavioral impulsivity/disinhibition (emergence test) and compulsive behavior (marble tests) were also carried out.
Closed, under finalization
CLCC Caen, Inserm 1086 anticipe
Inserm, Normandie Rouen University, Novartis