The involvement of homocysteine in stress-induced Aß precursor protein misprocessing and related cognitive decline in rats.

Chronic stress is a risk factor in the development of cognitive decline and even Alzheimer's disease (AD), although its underlying mechanism is not fully understood. Our previous data demonstrated that the level of homocysteine (Hcy) was significantly elevated in the plasma of stressed animals, which suggests the possibility that Hcy is a link between stress and cognitive decline. To test this hypothesis, we compared the cognitive function, plasma concentrations of Hcy, and the brain beta-amyloid (Aß) level between rats with or without chronic unexpected mild stress (CUMS). A lower performance by rats in behavioral tests indicated that a significant cognitive decline was induced by CUMS. Stress also disturbed the normal processing of Aß precursor protein (APP) and resulted in the accumulation of Aß in the brains of rats, which showed a positive correlation with the hyperhomocysteinemia (HHcy) that appeared in stressed rats. Hcy-targeting intervention experiments were used to verify further the involvement of Hcy in stress-induced APP misprocessing and related cognitive decline. The results showed that diet-induced HHcy could mimic the cognitive impairment and APP misprocessing in the same manner as CUMS, while Hcy reduction by means of vitamin B complex supplements and betaine could alleviate the cognitive deficits and dysregulation of Aß metabolism in CUMS rats. Taken together, the novel evidence from our present study suggests that Hcy is likely to be involved in chronic stress-evoked APP misprocessing and related cognitive deficits. Our results also suggested the possibility of Hcy as a target for therapy and the potential value of vitamin B and betaine intake in the prevention of stress-induced cognitive decline.

Antidepressant effect of electroacupuncture regulates signal targeting in the brain and increases brain-derived neurotrophic factor levels.

Electroacupuncture improves depressive behavior faster and with fewer adverse effects than antidepressant medication. However, the antidepressant mechanism of electroacupuncture remains poorly understood. Here, we established a rat model of chronic unpredicted mild stress, and then treated these rats with electroacupuncture at Yintang (EX-HN3) and Baihui (DU20) with sparse waves at 2 Hz and 0.6 mA for 30 minutes, once a day. We found increased horizontal and vertical activity, and decreased immobility time, at 2 and 4 weeks after treatment. Moreover, levels of neurotransmitters (5-hydroxytryptamine, glutamate, and γ-aminobutyric acid) and protein levels of brain-derived neurotrophic factor and brain-derived neurotrophic factor-related proteins (TrkB, protein kinase A, and phosphorylation of cyclic adenosine monophosphate response element binding protein) were increased in the hippocampus. Similarly, protein kinase A and TrkB mRNA levels were increased, and calcium-calmodulin-dependent protein kinase II levels decreased. These findings suggest that electroacupuncture increases phosphorylation of cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor levels by regulating multiple targets in the cyclic adenosine monophosphate response element binding protein signaling pathway, thereby promoting nerve regeneration, and exerting an antidepressive effect.

Changes of spacial learning and memory abilities and ultrastructure of hippocampus in perimenopausal depression model rats / 中华行为医学与脑科学杂志

Objective To observe changes of spacial learning and memory and the ultrastructure of hippocampus in perimenopausal depression model rats. Methods Thirty-six female SD rats were randomly divided into four groups(9 in each). Normal group wasn't given any stress, and stressed group was given isolation-housing in combination with chronic unexpected mild stress (CUMS) for 21 days. Ovariectomized group was given ovary resecting, and model group was made by resecting the ovaries of female rats, then giving isolation-housing in combination with 21 days of CUMS. Morris water maze test were used to test rats' behaviors. Light microscope and transmission electron microscope were used to observe the tissular structure of hippocampus. Results After ovaries resecting and 21 days of CUMS,the escape periods of rats in model group during the first three days ( (44.08 ± 18.29)s; ( 38.80 ± 19.07 ) s; ( 22.74 ± 14.13 ) s) were longer than ovariectomizd group ( (43.68 ± 10. 37 ) s; ( 20.28 ±17.75)s;(21.22 ± 11.91 )s] and normal group( (34.50 ± 11.08)s;(21.42 ± 14.32) s;( 13.94 ±9.76) s). HE staining showed that hippocampal pyramidal cell layer became thinner in rat model of depression,the gap between cells increased,and the cells arrayed in disorder,or loosely,even a large number of cells were lost. Transmission electron microscope showed that in rats of model group, hippocampal neurons were less, nuclear collapsed, the whole nuclear membrane was fuzzy and there were some local fractures in the nuclear membrane. Mitochondria within the cytoplasm were swelling and their ridges disappeared. Conclusion The decline of spacial learning and memory abilities in perimenopausal depression model rats might result from pathological changes in hippocampus.