MEK/ERKs Signaling Is Essential For Lithium-induced Neurite Outgrowth In N2a Cells

Background: Lithium chloride is used clinically to treat bipolar mooddisorder has100years of history, in recent years, it has also been used to treat a rangeof neurodegenerative diseases, such as stroke, AI Childs Alzheimer’s, Huntington’s,amyotrophic lateral sclerosis and other neurodegenerative diseases, with thedevelopment of society, these diseases incidence rate is increasing year by year.Neuronal damage, neural plasticity decreases nerve disease development is a keyprocess. In recent years a number of studies have shown that lithium chloride (LiCi)can improve the symptoms of neurodegenerative diseases. Previous studies we havefound in local anesthetic drug induced neuron injury model, LiCl has aneuroprotective effect, recent clinical experiments prove that LiCl can inhibit theprogression of amyotrophic lateral sclerosis, however, LiCi on neural protective effectand its mechanism is not clear.Methods: In order to verify our hypothesis we will mouse neuroma of N2acells in MEM culture medium were incubated with24h after adding differentconcentrations of LiCl (0,5,15,30uM), at various time points (12,24,36,48,60h) in200times under a light microscope with randomly selected different view photosstatistics. According to the above experimental results obtained with the mostappropriate lithium chloride concentration, using MEK/ERKs inhibitors of PD98059,U0126and PI3K/AKT inhibitor WM act on N2a cells, are grouped by Western Biotanalysis, later on various experimental protein quantification, and observe effects oflithium chloride on the neural protective effect is through which signal pathways mediated.Results: Lithium chloride can promote synaptic growth, which has a timedose dependent, mouse neuroma cell N2a was30uM lithium chloride treatment after30h, the typical synaptic growth, in LiCl treated N2a can be found in higher levels ofp-ERKs and p-Akt. in this test may be a discovery, inhibition of MEK/ERKspathways can be inhibited by LiCl mediated synaptic growth. More importantly, onPI3K/Akt signaling pathway inhibition increases LiCl mediated synaptic growth andactivation of ERKs. LiCl on neuronal synaptic growth effect is achieved byMEK/ERKs and PI3K/Akt signal pathway mediated by. Through this experiment, weconfirmed the increased LiCl time will increase N2a cells generated synaptic abilities,this shows LiCl may be neuroprotective effects promote synaptic growth.Conclusions: LiCl induced N2a promote synaptic growth is a time-anddose-dependent, LiCl mediated synaptic growth through the MEK/ERKs andPI3K/AKT signaling pathways regulating, and requires the activation of MEK/ERKssignaling pathway.