Synapsin III gene silencing redeems alpha-synuclein transgenic mice from Parkinson's disease-like phenotype

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Acquired semi-squamatization during chemotherapy suggests differentiation as a therapeutic strategy for bladder cancer

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Chronic brain stimulation rewarding experience ameliorates depression-induced cognitive deficits and restores aberrant plasticity in the prefrontal cortex

Background

Major depressive disorder (MDD) is a multifactorial disease which often coexists with cognitive deficits. Depression-induced cognitive deficits are known to be associated with aberrant reward processing, neurochemical and structural alterations. Recent studies have shown that chronic electrical stimulation of brain reward areas induces a robust antidepressant effect. However, the effects of repeated electrical self-stimulation of lateral hypothalamus - medial forebrain bundle (LH-MFB) on depression-induced cognitive deficits and associated neurochemical and structural alterations in the prefrontal cortex (PFC) are unknown.

Molecular mechanisms and cellular events involved in the neuroprotective actions of estradiol. Analysis of sex differences

Estradiol, either from peripheral or central origin, activates multiple molecular neuroprotective and neuroreparative responses that, being mediated by estrogen receptors or by estrogen receptor independent mechanisms, are initiated at the membrane, the cytoplasm or the cell nucleus of neural cells. Estrogen-dependent signaling regulates a variety of cellular events, such as intracellular Ca²⁺ levels, mitochondrial respiratory capacity, ATP production, mitochondrial membrane potential, autophagy and apoptosis. In turn, these molecular and cellular actions of estradiol are integrated by neurons and non-neuronal cells to generate different tissue protective responses, decreasing blood-brain barrier permeability, oxidative stress, neuroinflammation and excitotoxicity and promoting synaptic plasticity, axonal growth, neurogenesis, remyelination and neuroregeneration. Recent findings indicate that the neuroprotective and neuroreparative actions of estradiol are different in males and females and further research is necessary to fully elucidate the causes for this sex difference.     

Alterations in cortical and thalamic connections of somatosensory cortex following early loss of vision

Early loss of vision produces dramatic changes in the functional organization and connectivity of the neocortex in cortical areas that normally process visual inputs, such as the primary and second visual area. This loss also results in alterations in the size, functional organization, and neural response properties of the primary somatosensory area, S1. However, the anatomical substrate for these functional changes in S1 has never been described. In the present investigation, we quantified the cortical and subcortical connections of S1 in animals that were bilaterally enucleated very early in development, prior to the formation of retino-geniculate and thalamocortical pathways. We found that S1 receives dense inputs from novel cortical fields, and that the density of existing cortical and thalamocortical connections was altered. Our results demonstrate that sensory systems develop in tandem and that alterations in sensory input in one system can affect the connections and organization of other sensory systems. Thus, therapeutic intervention following early loss of vision should focus not only on restoring vision, but also on augmenting the natural plasticity of the spared systems.     

大补元煎通过上调BDNF/TrkB/CREB信号通路改善APP/PS1双转基因痴呆小鼠海马突触可塑性

目的:观察大补元煎对APP/PS1痴呆小鼠海马突触可塑性及脑源性神经营养因子(BDNF)/酪氨酸蛋白激酶受体B(TrkB)/环磷酸腺苷反应元件结合蛋白(CREB)信号通路的作用,并探讨其改善突触可塑性的可能机制。方法:将APP/PS1小鼠36只分为模型组、多奈哌齐组(6.5×10~(-4)g·kg~(-1)·d~(-1))和大补元煎组(13.2 g·kg~(-1)·d~(-1)),野生鼠12只设为正常组,正常组和模型组给予等体积生理盐水,各组连续灌胃30 d。应用Morris水迷宫检测各组小鼠的学习记忆能力,应用尼氏染色和高尔基染色观察海马区神经元和突触的病理形态变化,应用免疫荧光(IF)观察海马突触后致密蛋白95(PSD95)及突触素(SYN)的蛋白表达水平,采用蛋白免疫印迹法(Western blot)检测海马中BDNF,TrkB,CREB及磷酸化CREB(p-CREB)的蛋白表达水平。结果:与空白组比较,模型组小鼠平台潜伏期和游泳总路程增加(P0.01),穿越平台次数和目标象限停留时间减少(P0.01),小鼠海马CA3区神经元胞内尼氏体减少或消失,小鼠海马CA3区神经元及树突分支数量、树突棘密度减少(P0.01),小鼠海马SYN,PSD95,BDNF,TrkB及p-CREB的蛋白表达水平减少(P0.01)。与模型组比较,多奈哌齐组和大补元煎组小鼠平台潜伏期和游泳总路程减少(P0.05,P0.01),穿越平台次数和目标象限停留时间增加(P0.05,P0.01),小鼠海马CA3区神经元胞内尼氏体数量增多,小鼠海马CA3区神经元及树突分支数量,树突棘密度增加(P0.05,P0.01),小鼠海马SYN,PSD95,BDNF,TrkB及p-CREB的蛋白表达水平增加(P0.05,P0.01)。结论:大补元煎改善APP/PS1双转基因小鼠突触可塑性的机制可能与其上调小鼠海马中BDNF/TrkB/CREB信号通路有关。     

Afterword: Tough Questions; Hard Problems; Incremental Progress

The papers in this issue have specific and focused targets that are essential for making incremental progress on the very difficult problem of identifying the coevolutionary interactions of cognition and culture. The purpose of this paper is to discern the shape of a few of the large problems that loom over these more narrowly focussed papers, and to explain and assess the ways these papers contribute to their solution. The background problems described are (a) the character of the selective interactions between the evolution of culture and of cognition; (b) the special features of cumulative cultural evolution; and (c) the place of language in an account of cognition–culture coevolution. The paper ends with some reflections on the extraordinarily difficult challenge of testing scenarios in this field.     

Hubs disruption in mesial temporal lobe epilepsy. A resting‐state fMRI study on a language‐and‐memory network

Mesial temporal lobe epilepsy (mTLE) affects the brain networks at several levels and patients suffering from mTLE experience cognitive impairment for language and memory. Considering the importance of language and memory reorganization in this condition, the present study explores changes of the embedded language‐and‐memory network (LMN) in terms of functional connectivity (FC) at rest, as measured with functional MRI. We also evaluate the cognitive efficiency of the reorganization, that is, whether or not the reorganizations support or allow the maintenance of optimal cognitive functioning despite the seizure‐related damage. Data from 37 patients presenting unifocal mTLE were analyzed and compared to 48 healthy volunteers in terms of LMN‐FC using two methods: pairwise correlations (region of interest [ROI]‐to‐ROI) and graph theory. The cognitive efficiency of the LMN‐FC reorganization was measured using correlations between FC parameters and language and memory scores. Our findings revealed a large perturbation of the LMN hubs in patients. We observed a hyperconnectivity of limbic areas near the dysfunctional hippocampus and mainly a hypoconnectivity for several cortical regions remote from the dysfunctional hippocampus. The loss of FC was more important in left mTLE (L‐mTLE) than in right (R‐mTLE) patients. The LMN‐FC reorganization may not be always compensatory and not always useful for patients as it may be associated with lower cognitive performance. We discuss the different connectivity patterns obtained and conclude that interpretation of FC changes in relation to neuropsychological scores is important to determine cognitive efficiency, suggesting the concept of “connectome” would gain to be associated with a “cognitome” concept.     

PI3K-AKT信号通路与抑郁症的关系及中医干预作用研究进展

综述PI3K-AKT信号通路与抑郁症的关系及中医干预作用研究进展。研究发现,抑郁症的发病机制与PI3K-AKT信号通路密切相关,通过促进PI3K-AKT信号通路激活,能够改善突触可塑性,进而对抑郁行为的改善起促进作用。针灸、中药、方剂对抑郁症有一定的疗效,通过促进PI3K-AKT激活改善突触可塑性是其改善抑郁状态的作用机制之一。