Anesthetics are used extensively in surgeries and related procedures to prevent
pain. However, there is some concern regarding neuronal degeneration and cognitive deficits arising from regular
anesthetic exposure. Recent studies have indicated that
brain-derived neurotrophic factor (
BDNF) and
cyclic AMP response element-binding protein (CREB) are involved in learning and memory processes.
Genistein, a plant-derived
isoflavone, has been shown to exhibit
neuroprotective effects. The present study was performed to examine the protective effect of
genistein against
isoflurane-induced neurotoxicity in rats. Neonatal rats were exposed to
isoflurane (0.75%, 6 hours) on postnatal day 7 (P7). Separate groups of rat pups were orally administered
genistein at doses of 20, 40, or 80 mg/kg
body weight from P3 to P15 and then exposed to
isoflurane anesthesia on P7. Neuronal apoptosis was detected by TUNEL assay and FluoroJade B staining following
isoflurane exposure.
Genistein significantly reduced apoptosis in the hippocampus, reduced the expression of proapoptotic factors (Bad, Bax, and cleaved
caspase-3), and increased the expression of Bcl-2 and Bcl-xL. RT-PCR analysis revealed enhanced
BDNF and TrkB
mRNA levels.
Genistein effectively upregulated cAMP levels and phosphorylation of CREB and TrkB, leading to activation of cAMP/CREB-
BDNF-TrkB signaling. PI3K/Akt signaling was also significantly activated.
Genistein administration improved general behavior and enhanced learning and memory in the rats. These observations suggest that
genistein exerts
neuroprotective effects by suppressing
isoflurane-induced neuronal apoptosis and by activating cAMP/CREB-
BDNF-TrkB-PI3/Akt signaling.