Transforming growth factor β1 restores hippocampal synaptic plasticity and memory loss in an Alzheimer's disease model through the PI3K/Akt signaling pathway

Alzheimer's disease (AD) is a type of neurodegenerative disorder that exhibits gradual memory deprivation. The hallmarks of AD include the presence of neurofibrillary tangles, amyloid beta-plaques, and neuronal loss. Amyloid beta oligomers (A beta Os) have been reported to trigger synaptotoxicity, eventually resulting in reduced dendritic spine density (DSD), thus confirming the speculation that synapsis impairment is a causative factor of AD development. Transforming growth factor (TGF) beta 1, an immunosuppressive cytokine, has been shown to play a neuroprotective in an AD model. Studies have described that TGF beta 1 was positively relevant to the dendritic spine number in mice. Furthermore, other studies have indicated the role of the PI3K/Akt pathway is involved in synaptic plasticity (SP) and cognitive damage in mice with seizures. Several studies have also reported that TGF beta 1 could regulate the PI3K signaling pathway. However, the underlying mechanisms involving TGF beta 1 and the PI3K/Akt signaling pathway in altering memory and SP in AD models are not clear. In the present study, TGF beta 1 was injected into the intracerebroventricle (ICV) and A beta 1-42 was injected into both sides of the hippocampus to assess the neuroprotective component of TGF beta 1. TGF beta 1 administration after the A beta 1-42 injection restored the memory loss, as investigated by the Morris water maze test, and the deterioration of SP, as detected by Golgi staining. Then, western blot was performed to evaluate the expression levels of p-Akt, Akt, and p-Ser-9-GSK3 beta. Results showed that TGF beta 1 administration restored the memory loss and assisted in the reduction of DSD caused due to the A beta 1-42 injection in the hippocampus. Additionally, the ratio of p-Akt/Akt p-Ser-9-GSK3 beta was enhanced by the A beta 1-42 injection, which was later decreased by TGF beta 1 treatment. Therefore, TGF beta 1 prevented the decrease in DSD in the hippocampus and the memory deprivation through the PI3K/Akt signaling pathway.