Melatonin ameliorates anxiety and depression-like behaviors and modulates proteomic changes in triple transgenic mice of Alzheimer's disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disease accompanied by neuropsychiatric symptoms, such as anxiety and depression. The levels of melatonin decrease in brains of AD patients. The potential effect of melatonin on anxiety and depression behaviors in AD and the underlying mechanisms remain unclear. In this study, we treated 10-month-old triple transgenic mice of AD (3xTg-AD) with melatonin (10 mg/kg body weight/day) for 1 month and explored the effects of melatonin on anxiety and depression-like behaviors in 3xTg-AD mice and the protein expression of hippocampal tissues. The behavioral test showed that melatonin ameliorated anxiety and depression-like behaviors of 3xTg-AD mice as measured by open field test, elevated plus maze test, forced swimming test, and tail suspension test. By carrying out two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry, we revealed a total of 46 differentially expressed proteins in hippocampus between the wild-type (WT) mice and non-treated 3xTg-AD mice. A total of 21 differentially expressed proteins were revealed in hippocampus between melatonin-treated and non-treated 3xTg-AD mice. Among these differentially expressed proteins, glutathione S-transferase P 1 (GSTP1) (an anxiety-associated protein) and complexin-1 (CPLX1) (a depression-associated protein) were significantly down-regulated in hippocampus of 3xTg-AD mice compared with the WT mice. The expression of these two proteins was modulated by melatonin treatment. Our study suggested that melatonin could be used as a potential candidate drug to improve the neuropsychiatric behaviors in AD via modulating the expression of the proteins (i.e. GSTP1 and CPLX1) involved in anxiety and depression behaviors. © 2017 BioFactors, 43(4):593-611, 2017.

Nie L ，Wei G ，Peng S ，Qu Z ，Yang Y ，Yang Q ，Huang X ，Liu J ，Zhuang Z ，Yang X ... -  《-》

Identification of the key molecules involved in chronic copper exposure-aggravated memory impairment in transgenic mice of Alzheimer's disease using proteomic analysis.

Yu J ，Luo X ，Xu H ，Ma Q ，Yuan J ，Li X ，Chang RC ，Qu Z ，Huang X ，Zhuang Z ，Liu J ，Yang X ... -  《-》

Ginsenoside Rg1 Ameliorates Behavioral Abnormalities and Modulates the Hippocampal Proteomic Change in Triple Transgenic Mice of Alzheimer's Disease.

Nie L ，Xia J ，Li H ，Zhang Z ，Yang Y ，Huang X ，He Z ，Liu J ，Yang X ... -  《-》

Depressive-like behavior is paired to monoaminergic alteration in a murine model of Alzheimer's disease.

Neuropsychiatric signs are critical in primary caregiving of Alzheimer patients and have not yet been fully investigated in murine models. 18-month-old 3×Tg-AD male mice and their wild-type male littermates (non-Tg) were used. The open field test and the elevated plus maze test were used to evaluate anxiety-like behaviors, whereas the Porsolt forced swim test, the tail suspension test, and the sucrose preference test for antidepressant/depression-coping behaviors. Neurochemical study was conducted by microdialysis in freely-moving mice, analyzing the basal and K(+)-stimulated monoamine output in the frontal cortex and ventral hippocampus. Moreover by immunohistochemistry, we analysed the expression of Tyrosin hydroxylase and Tryptophan hydroxylase, which play a key role in the synthesis of monoamines. Aged 3×Tg-AD mice exhibited a higher duration of immobility in the forced swim and tail suspension tests (predictors of depression-like behavior) which was not attenuated by a noradrenaline reuptake inhibitor, desipramine. In the sucrose preference test, 3×Tg-AD mice showed a significantly lower sucrose preference compared to the non-Tg group, without any difference in total fluid intake. In contrast, the motor functions and anxiety-related emotional responses of 3×Tg-AD mice were normal, as detected by the open-field and elevated plus-maze tests. To strengthen these results, we then evaluated the monoaminergic neurotransmissions by in vivo microdialysis and immunohistochemistry. In particular, with the exception of the basal hippocampal dopamine levels, 3×Tg-AD mice exhibited a lower basal extracellular output of amines in the frontal cortex and ventral hippocampus and also a decreased extracellular response to K(+) stimulation. Such alterations occur with obvious local amyloid-β and tau pathologies and without gross alterations in the expression of Tyrosin and Tryptophan hydroxylase. These results suggest that 3×Tg-AD mice exhibit changes in depression-related behavior involving aminergic neurotrasmitters and provide an animal model for investigating AD with depression.

Romano A ，Pace L ，Tempesta B ，Lavecchia AM ，Macheda T ，Bedse G ，Petrella A ，Cifani C ，Serviddio G ，Vendemiale G ，Gaetani S ，Cassano T ... -  《-》

Identification of Novel Key Molecules Involved in Spatial Memory Impairment in Triple Transgenic Mice of Alzheimer's Disease.

Ying M ，Sui X ，Zhang Y ，Sun Q ，Qu Z ，Luo X ，Chang RC ，Ni J ，Liu J ，Yang X ... -  《-》