ABSTRACT
Homocysteine (Hcy) is an independent and serious risk factor for dementia, including Alzheimer's disease (AD), but the precise mechanisms are still poorly understood. In the current study, we observed that the permissive histone mark trimethyl histone H3 lysine 4 (H3K4me3) and its methyltransferase KMT2B were significantly elevated in hyperhomocysteinemia (HHcy) rats, with impairment of synaptic plasticity and cognitive function. Further research found that histone methylation inhibited synapse-associated protein expression, by suppressing histone acetylation. Inhibiting H3K4me3 by downregulating KMT2B could effectively restore Hcy-inhibited H3K14ace in N2a cells. Moreover, chromatin immunoprecipitation revealed that Hcy-induced H3K4me3 resulted in ANP32A mRNA and protein overexpression in the hippocampus, which was regulated by increased transcription Factor c-fos and inhibited histone acetylation and synapse-associated protein expression, and downregulating ANP32A could reverse these changes in Hcy-treated N2a cells. Additionally, the knockdown of KMT2B restored histone acetylation and synapse-associated proteins in Hcy-treated primary hippocampal neurons. These data have revealed a novel crosstalk mechanism between KMT2B-H3K4me3-ANP32A-H3K14ace, shedding light on its role in Hcy-related neurogenerative disorders.
ABSTRACT
Growing evidence suggests that macroautophagy/autophagy-lysosomal pathway deficits contribute to the accumulation of amyloid-ß (Aß) in Alzheimer disease (AD). Aerobic exercise (AE) has long been investigated as an approach to delay and treat AD, although the exact role and mechanism are not well known. Here, we revealed that AE could reverse autophagy-lysosomal deficits via activation of ADRB2/ß2-adrenergic receptor, leading to significant attenuation of amyloid-ß pathology in APP-PSEN1/PS1 mice. Molecular mechanism research found that AE could reverse autophagy deficits by upregulating the AMP-activated protein kinase (AMPK)-MTOR (mechanistic target of rapamycin kinase) signaling pathway. Moreover, AE could reverse V-ATPase function by upregulating VMA21 levels. Inhibition of ADRB2 by propranolol (antagonist, 30 µM) blocked AE-attenuated Aß pathology and cognitive deficits by inhibiting autophagy-lysosomal flux. AE may mitigate AD via many pathways, while ADRB2-VMA21-V-ATPase could improve cognition by enhancing the clearance of Aß through the autophagy-lysosomal pathway, which also revealed a novel theoretical basis for AE attenuating pathological progression and cognitive deficits in AD.
ABSTRACT
The stand environment and tree growth could be changed as well as carbon storage be affected by thinning. Thus it is important to conduct the research on changes of carbon stock in plantations after thinning for assessing the dynamics of forest ecosystem carbon pool. The carbon storage and its distribution of various components in 22-year-old Cunninghamia lanceolata plantations were studied with control and different treatments such as moderate and heavy thinning. Moderate (thinning intensity was 35%) and heavy (thinning intensity was 50%) thinning treatments were conducted twice at the age of 7 and 14 years, respectively. The stand of control was thinned 15% in the 14th year. The results showed that the proportion of stem carbon storage increased with the increasing thinning intensity, while the proportion of carbon storage in branches, leaves and roots slightly decreased, which suggested that thinning was beneficial for carbon stocking in stem. However, the carbon storage in arbor layer decreased with the thinning intensity in C. lanceolata plantation under moderate and heavy thinning treatments, accounted for 89.0% and 83.1% of the control, respectively. The arbor carbon storage decreased in followed two years after the first thinning. The carbon storage in arbor layer had a fast recovery rate within eight years after the second thinning, and the increment of carbon storage in arbor layer had no difference with the control for the heavy thinning treatment. The carbon storage in understory vegetation, litter and soil layers also had no significant difference under the different thinning treatments. Generally total ecosystem carbon storage under the control, moderate and heavy thinning treatments reached 169.34, 156.65 and 154.37 t x hm(-2), respectively. There was no significant difference among the three treatments. Therefore, it could be concluded that the carbon storage in C. lanceolata plantation did not reduce after thinning in more than 15 years.
