Animal model of posterior cingulate cortex hypometabolism implicated in amnestic MCI and AD

The posterior cingulate cortex (PCC) is the brain region displaying the earliest sign of energy hypometabolism in patients with amnestic mild cognitive impairment (MCI) who develop Alzheimer’s disease (AD). In particular, the activity of the mitochondrial respiratory enzyme cytochrome oxidase (C.O.) is selectively inhibited within the PCC in AD. The present study is the first experimental analysis designed to model in animals the localized cortical C.O. inhibition found as the earliest metabolic sign of early-stage AD in human neuroimaging studies. Rats were used to model local inhibition of C.O. by direct injection of the C.O. inhibitor sodium azide into the PCC. Learning and memory were examined in a spatial holeboard task and brains were analyzed using quantitative histochemical, morphological and biochemical techniques. Behavioral results showed that sodium azide-treated rats were impaired in their memory of the baited pattern in probe trials as compared to their training scores before treatment, without non-specific behavioral differences. Brain analyses showed that C.O. inhibition was specific to the PCC, and sodium azide increased lipid peroxidation, gliosis and neuron loss, and lead to a network functional disconnection between the PCC and interconnected hippocampal regions. It was concluded that impaired memory by local C.O. inhibition in the PCC may serve to model in animals a metabolic lesion similar to that found in patients with amnestic MCI and early-stage AD. This model may be useful as an in vivo testing platform to investigate neuroprotective strategies to prevent or reduce the amnestic effects produced by posterior cingulate energy hypometabolism.     

赖氨酰氧化酶在动脉粥样硬化中的作用

赖氨酰氧化酶(lysyl oxidase,LOX)是一种铜依赖性氨基氧化酶,在多个组织器官中均有表达,能参与催化细胞外基质(extracellular matrix,ECM)中胶原和弹性纤维的赖氨酸残基交联,以维持细胞外基质的结构和功能正常。新近研究发现LOX与动脉粥样硬化亦有紧密关系。本文就LOX在动脉粥样硬化发生、发展过程中的联系作一综述。     

Violence Exposure and the Development of School-Related Functioning: Mental Health, Neurocognition, and Learning

The relation between history of violence exposure and the development of academic and mental health problems is explored. Violence exposed children have an increased risk of developing school-related problems including: mental health problems, learning disabilities, language impairments, and other neurocognitive problems. These problems interact to create a complex web of deficits and disabilities where intervention access points are difficult to assess. Often mental health problems and academic problems develop in parallel. Timing of violence exposure and the developmental stage of the child during exposure complicate our understanding of the underlying mechanism. A model is presented that explores pathways linking violence exposure to aspects of school-related functioning, both academically and behaviorally. Early life stress, in the form of violence exposure, is related to neurocognitive deficits, including executive functioning and problems in self-regulation. Deficits in self-regulation at the level of behavior, and cognitive control and executive functioning, at the level of brain processing, are related to both academic and mental health problems, suggesting a possible psychological mechanism. Biological mechanisms are also included in the model to illustrate the contribution of the stress response, neuroendocrine system response, and neuroanatomical structural and functional impairments associated with violence exposure.     

Effect of MAO A deficiency on different kinds of aggression and social investigation in mice

Monoamine oxidase A (MAO A) degrades serotonin, dopamine and noradrenaline, factors critically involved in the regulation of aggression. Different kinds of aggression were investigated in Tg8, a transgenic mouse strain lacking a functional MAO A gene. MAO A-deficient mice differ from wild-type C3H/HeJ (C3H) in terms of showing higher territorial, predatory and isolation-induced aggression. Tg8 demonstrated shorter latencies to cricket killing and to the first attack after 6 weeks isolation than C3H mice. In the resident-intruder paradigm, MAO A-lacking mice were more aggressive than C3H when tested as intruders. In contrast to C3H, attack in Tg8 mice did not depend on different aggressiveness of intruders of BALB/c, A/Sn and C3H strains. Tg8 mice displayed no increase in aggression but demonstrated reduced social investigation towards anesthetized, as well as towards juvenile BALB/c males. Thus, MAO A deficiency in Tg8 mice is accompanied by increased expression of different kinds of aggression, as well as by disruption of normal pattern of social interaction.