Maf1, a general transcriptional regulator and mTOR downstream effector, is highly expressed in the hippocampus and cortex, but the function of Maf1 in neurons is not well elucidated. Here, we first demonstrate that Maf1 plays a central role in the inhibition of dendritic morphogenesis and the growth of dendritic spines both in vitro and in vivo. Furthermore, Maf1 downregulation paradoxically leads to activation of AKT-mTOR signaling, which is mediated by decreased PTEN expression. Moreover, we confirmed that Maf1 could regulate the activity of PTEN promoter by luciferase reporter assay, and proved that Maf1 could bind to the promoter of PTEN by ChIP-PCR experiment. We also demonstrate that expression of Maf1 in the hippocampus affects learning and memory in mice. Taken together, we show for the first time that Maf1 inhibits dendritic morphogenesis and the growth of dendritic spines through AKT-mTOR signaling by increasing PTEN expression.

Repetitive traumatic brain injury (rTBI) is a major health care concern that causes substantial neurological impairment. To better understand rTBI, we introduced a new model of rTBI in mice induced by sudden rotation in the coronal plane combined with lateral translation delivered twice at an interval of 24 h. By routine histology, histological examination of Prussian blue-stained sections revealed the presence of microbleed in the corpus callosum and brain stem. Amyloid precursor protein (β-APP) and neurofilament heavy-chain (NF-200) immunohistochemistry demonstrated axonal injury following rTBI. Swelling, waving, and enlargement axons were observed in the corpus callosum and brain stem 24 h after injury by Bielschowsky staining. Ultrastructural studies by electron microscopy provided further insights into the existence and progression of axonal injury. rTBI led to widespread astrogliosis and microgliosis in white matter, as well as significantly increased levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β. rTBI mice showed a significantly increased loss of righting reflex (LRR) duration within each time point compared with that of sham animals, which was under 15 min. rTBI mice exhibited depression-like behavior at 1 month. rTBI mice also demonstrated deficits in MWM testing. These results suggested that this model might be suitable for investigating rTBI pathophysiology and evaluating preclinical candidate therapeutics.

Background and purpose The objective of the study was to investigate the relationship between IL1R2 rs34043159 and Alzheimer’s disease (AD) in the Chinese population. Methods A total of 500 AD patients and 500 healthy controls were recruited. The SNaPshot technique was used to detect IL1R2 rs34043159. Results The dominant and recessive models of IL1R2 rs34043159 were associated with AD with or without adjustment of age, gender and education [dominant model, P = 0.019, odds ratio (OR) 1.42, 95% confidence interval (CI) 1.06–1.89, adjusted; recessive model, P = 0.011, OR 0.69, 95% CI 0.51–0.92, adjusted]. The recessive model of IL1R2 rs34043159 was associated with early‐onset AD (EOAD) with or without adjustment of age, gender and education (recessive model, P = 0.038, OR 0.60, 95% CI 0.37–0.97, adjusted). The additive model was associated with late‐onset AD (LOAD) (P = 0.041). The dominant model of IL1R2 rs34043159 was associated with LOAD with or without adjustment of age, gender and education (dominant model, P = 0.005, OR 1.68, 95% CI 1.17–2.44, adjusted). Conclusion An association between the dominant and recessive model of IL1R2 rs34043159 and AD was found. The recessive model of IL1R2 rs34043159 was associated with EOAD. The additive and dominant models of IL1R2 rs34043159 were associated with LOAD.