Abstract：OBJECTIVE: To study the effects of PI3K/Akt signaling pathway inhibitor wortmannin on long-term learning and memory abilities in neonatal rats with hypoxic-ischemic brain damage (HIBD). METHODS: Forty-eight neonatal rats were randomly assigned to blank control (n=8), sham-operated (n=8), HIBD model (n=10), HIBD+DMSO (dimethyl sulfoxide, n=8) and HIBD+wortmannin groups (n=8). Wortmannin (2 μL) was injected to the left hippocampus 30 minutes before HIBD inducement in the HIBD+wortmannin group. The Morris water maze test was used to examine the long-term learning and memory abilities at the age of 28 days. RESULTS: With the increased number of swimming, the escape latency was shortened in various groups. From the second day, the escape latency in the HIBD+wortmannin group was significantly longer than that in the sham-operated and the blank control groups (P<0.05), and the differences increased with the time. On the fourth day, there were significant differences in the escape latency between the HIBD+wortmannin group and the HIBD+DMSO group as well as the HIBD model group (P<0.05). On the eighth day (retention trial), there were the most obvious differences in the escape latency between the HIBD+wortmannin group with the other four groups. In the space exploration test, the number of times crossing the former platform location within 120 seconds after removing the platform in the HIBD+DMSO and the HIBD model group was lower than the sham-operated and the blank control groups (P<0.05). The HIBD+wortmannin group showed lower number of times crossing the former platform location compared with the HIBD+DMSO and the HIBD model groups (P<0.05), as well as the sham-operated and the blank control groups (P<0.01). CONCLUSIONS: P13K/Akt signaling pathway inhibitor wortmannin can aggravate the cognitive impairments, thus affecting adversely long-term learning and memory abilities in neonatal rats with HIBD.
YAO Dan,HE Xue,WANG Jin-Hu et al. Effects of PI3K/Akt signaling pathway on learning and memory abilities in neonatal rats with hypoxic-ischemic brain damage[J]. CJCP, 2011, 13(5): 424-427.
［1］McAuliffe JJ, Miles L, Vorhees CV. Adult neurological function following neonatal hypoxia-ischemia in a mouse model of the term neonate: water maze performance is dependent on separable cognitive and motor components［J］. Brain Res, 2006, 1118(1): 208-221.
［2］Sharrard RM, Maitland NJ. Regulation of protein kinase B activity by PTEN and SHIP2 in human prostate-derived cell lines［J］. Cell Signal, 2007, 19(1):129-138.
［3］Janas ML, Hodson D, Stamataki Z, Hill S, Welch K, Gambardella L, et al. The effect of deleting p110delta on the phenotype and function of PTEN-deficient B cells［J］. J Immunol, 2008, 180(2):739-746.
［9］Li L, Qu Y, Mao M, Xiong Y, Mu D. The involvement of phosphoinositid 3-kinase/Akt pathway in the activation of hypoxiainducible factor-1alpha in the developing rat brain after hypoxia-ischemia［J］. Brain Res, 2008, 1197: 152-158.
［11］Rice JE 3rd, Vannucci RC, Brierley JB. The influence of immatuity on hypoxic-ischemic brain damage in the rat［J］．Ann Neurol, 1981, 9（2）: 131-141.
［12］Nakajima W, Ishida A, Lange MS, Gabrielson KL, Wilson MA, Martin LJ, et al. Apoptosis has a prolonged role in the neurodegeneration after hypoxic-ischemia in the newborn rat［J］．J Neurosci, 2000, 20(21): 7994-8004.
［13］Kitagawa H, Warita H, Sasaki C, Zhang WR, Sakai K, Shiro Y, et al. Immunoreactive Akt, PI3-K and ERK protein kinase expression in ischemic rat brain［J］. Neurosci Lett, 1999, 274(1): 45-48.
［14］Li F, Omori N, Jin G, Wang SJ, Sato K, Nagano I, et al. Cooperative expression of survival p-ERK and p-Akt signals in rat brain neurons after transient MCAO［J］. Brain Res, 2003, 962(1-2): 21-26.
［15］Jiang Z, Zhang Y, Chen XQ, Lam PY, Yang H, Xu Q, et al. Apoptosis and activation of Erkl/2 and Akt in astrocytes postischemia［J］. Neurochem Res, 2003, 28(6): 831-837.
