BackgroundExercise induces plasticity in the hippocampus, which includes increases in neurogenesis, the proliferation of new neurons, and angiogenesis, the sprouting of new capillaries from preexisting blood vessels. Following exercise, astrocytes also undergo morphological changes that parallel the events occurring in the neurovascular system. Interestingly, there have also been reports of apoptosis in the hippocampus following aerobic exercise. This experiment aimed to identify which population of hippocampal cells undergoes apoptosis after an acute bout of exercise.MethodsCleaved caspase‐3, a terminal protein in the apoptotic cascade, was initially used to identify apoptotic cells in the hippocampus after rats completed an acute bout of exercise. Next, the proportion of immature neurons, adult neurons, astrocytes, or radial glia‐like cells expressing cleaved caspase‐3 was quantified. TUNEL staining was completed as a second measure of apoptosis.ResultsFollowing exercise, cleaved caspase‐3 expression was increased in the CA1 and DG regions of the hippocampus. Cleaved caspase‐3 was not highly expressed in neuronal populations, and expression was not increased in these cells postexercise. Instead, cleaved caspase‐3 was predominantly expressed in astrocytes. Following exercise, there was an increased number of cleaved caspase‐3 positive astrocytes in DG and CA1, and cleaved caspase‐3 positive radial glia‐like cells located in the subgranular zone. To determine whether cleaved caspase‐3 expression in these glial cells was associated with apoptosis, a TUNEL assay was completed. TUNEL staining was negligible in all groups and did not mirror the pattern of caspase‐3 labeling.ConclusionsCleaved caspase‐3 expression was detected largely in non‐neuronal cell populations, and the pattern of cleaved caspase‐3 expression did not match that of TUNEL. This suggests that after exercise, cleaved caspase‐3 expression may serve a nonapoptotic role in these hippocampal astrocytes and radial glia‐like cells. It will be important to identify the function of exercise‐induced cleaved caspase‐3 expression in the future experiments.

Bexarotene has shown inhibition of lung and mammary gland tumorigenesis in preclinical models and in clinical trials. The main side effects of orally administered bexarotene are hypertriglyceridemia and hypercholesterolemia. We previously demonstrated that aerosolized bexarotene administered by nasal inhalation has potent chemopreventive activity in a lung adenoma preclinical model without causing hypertriglyceridemia. To facilitate its future clinical translation, we modified the formula of the aerosolized bexarotene with a clinically relevant solvent system. This optimized aerosolized bexarotene formulation was tested against lung squamous cell carcinoma mouse model and lung adenocarcinoma mouse model and showed significant chemopreventive effect. This new formula did not cause visible signs of toxicity and did not increase plasma triglycerides or cholesterol. This aerosolized bexarotene was evenly distributed to the mouse lung parenchyma, and it modulated the microenvironment in vivo by increasing the tumor-infiltrating T cell population. RNA sequencing of the lung cancer cell lines demonstrated that multiple pathways are altered by bexarotene. For the first time, these studies demonstrate a new, clinically relevant aerosolized bexarotene formulation that exhibits preventive efficacy against the major subtypes of lung cancer. This approach could be a major advancement in lung cancer prevention for high risk populations, including former and present smokers.

No abstract

No abstract

No abstract