Depressed hippocampal MEK/ERK phosphorylation correlates with impaired cognitive and synaptic function in zinc-deficient rats

Abstract

An experiment was performed to observe changes of mitogen-activated protein kinase ERK (MEK)/extracellular signal-regulated kinase (ERK) signaling pathways in the hippocampus of zinc-deficient (ZD) rats and the correlation with cognitive dysfunction. Forty-four male weanling Wistar rats were randomly assigned to ZD (n = 22) and control (pair-fed, n = 22) groups. After a 4-week treatment, Y-maze was used to test the spatial memory of the rats. The long-term potentiation (LTP) in rat hippocampal dentate gyrus was observed simultaneously. pMEK, pERK1/2, and pCREB protein levels were examined by Western blot assays. The results demonstrated that the latency period in Y-maze was significantly shorter for the ZD rats. LTP amplitude in the ZD group decreased significantly compared with the control group. pMEK, pERK1/2, and pCREB protein expression of hippocampus in the ZD group decreased significantly. The results implicated a possibility that zinc deficiency-induced cognitive and synaptic impairment may be relevant to the MEK/ERK signaling pathway.

Effects of maternal mild zinc deficiency and different ways of zinc supplementation for offspring on learning and memory

“…The results from the MWM test revealed that zinc-deficient rats exhibited defects in memory behavior. This is consistent with previous reports showing that dietary zinc deficiency appears to damage learning and memory processes ( 25 – 27 ). Previous studies evaluated the effects of maternal zinc deprivation during critical periods of rapid fetal and infant brain growth, which differed from the present study by the degree of zinc deficiency during different periods.…”

“…Previous studies evaluated the effects of maternal zinc deprivation during critical periods of rapid fetal and infant brain growth, which differed from the present study by the degree of zinc deficiency during different periods. Animal research has shown that severe maternal zinc deficiency (zinc<1 µg/g diet) in early pregnancy, a period of fetal organogenesis, results in fetal brain malformation ( 25 ). Pregnant animals given severe zinc-deficient diets also exhibited poor performance of shock-induced learning tasks during the last period of gestation (14–20 days) or during lactation, a period which would not affect organogenesis, but would be critical for brain growth ( 26 , 27 ).…”

“…All these studies showed consistent results despite different designs. Cognitive impairment may be induced by the decrease in brain protein synthesis and the total amount of brain lipids in the pups ( 25 ).…”

The Role of Zinc in Mood Disorders

“…Growing evidence implicated the impact of zinc dyshomeostasis in the onset and progression of AD pathogenesis [118][119][120][121]. Zinc deficiency was proved to induce hippocampal neuronal apoptosis, synaptic loss, and learning and memory impairment [101,120,122,123]. A recent study demonstrated that zinc deficiency aggravated Aβ aggregation and tau-phosphorylation in 10-month-old APP/ PS1 transgenic mice, leading to learning and memory impairment [83].…”

Mikronährstoffe und Gehirn

“…Ein moderater Zinkmangel bei Rhesusaffen bewirkt typische Verhaltensänderungen, die auf eine Störung der Neurogenese im Hippocampus schließen lassen (Fuglestad et al 2010). Ein moderater Zinkmangel bei trächtigen Ratten hat bereits Störungen der räumlichen Orientierung bei den Neugeborenen zur Folge (Jiang et al 2011;Yu et al 2013). Eine Supplementierung von Zink konnte sowohl die durch den Mangel ausgelösten morphologischen Veränderungen im Hippocampus verhindern als auch die kognitiven Störungen.…”