Neuroscience
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Survivin, a unique member of the inhibitor of the apoptosis protein (IAP) family, has been suggested to play a crucial role in promoting the cell cycle and mediates mitosis during embryonic development. However, the role of survivin following traumatic brain injury (TBI) in adult neurogenesis and apoptosis in the mouse dentate gyrus (DG) remains only partially understood. We adopted adenovirus-mediated RNA interference (RNAi) as a means of suppressing the expression of survivin and observed its effects on adult regeneration and neurological function in mice after brain injury. ⋯ Furthermore, downregulation of survivin results in a significant increase in programmed cell death in the DG, as assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and 4',6-diamidino-2-phenylindole (DAPI) double staining. The Morris water maze (MWM) test was adopted to evaluate neurological function, which confirmed that knockdown of survivin worsened the memory capacity that was already compromised following TBI. Survivin in adult mice brains after TBI can be successfully down-regulated by RNAi, which inhibited adult hippocampal neurogenesis, promoted apoptotic cell death, and resulted in a negative role in the recovery of dysfunction following injury.
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Inter-connected brain areas coordinate to process information and synchronized neural activities engage in learning and memory processes. Recent electrophysiological studies in rodents have implicated hippocampal-prefrontal connectivity in anxiety, spatial learning and memory-related tasks. In human patients with schizophrenia and autism, robust reduced connectivity between the hippocampus (HPC) and prefrontal cortex (PFC) has been reported. ⋯ Cx3cr1 knockout mice showed reduced baseline PFC driving to the dHPC compared to their wild-type littermates. PFC to dHPC causality could predict the actual time spent interacting with the social stimuli. The current findings indicate that directed oscillatory activities between the PFC and the HPC have task-dependent roles during exploration in the anxiety test and in the social interaction test.
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Review
Circuitry and plasticity of the dorsal horn - Toward a better understanding of neuropathic pain.
Maladaptive plasticity within the dorsal horn (DH) of the spinal cord is a key substrate for development of neuropathic pain following peripheral nerve injury. Advances in genetic engineering, tracing techniques and opto-genetics are leading to a much better understanding of the complex circuitry of the spinal DH and the radical changes evoked in such circuitry by nerve injury. ⋯ Understanding which changes relate to specific disease-states is essential, and recent work has aimed to stratify patient populations in a mechanistic fashion. In this review we will discuss how such pathophysiological mechanisms may lead to the distressing sensory phenomena experienced by patients suffering neuropathic pain, and the relationship of such mechanisms to current and potential future treatment modalities.
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Review
The role of inflammation and microglial activation in the pathophysiology of psychiatric disorders.
Psychiatric disorders, including major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia, affect a significant percentage of the world population. These disorders are associated with educational difficulties, decreased productivity and reduced quality of life, but their underlying pathophysiological mechanisms are not fully elucidated. Recently, studies have suggested that psychiatric disorders could be considered as inflammatory disorders, even though the exact mechanisms underlying this association are not known. ⋯ Thus, it is possible that the inflammatory response from microglial activation can contribute to brain pathology, as well as influence treatment responses. This review will highlight the role of inflammation in the pathophysiology of psychiatric disorders, such as MDD, BD, schizophrenia, and autism. More specifically, the role of microglial activation and associated molecular cascades will also be discussed as a means by which these neuroinflammatory mechanisms take place, when appropriate.
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Memory formation is a protracted process in which recently acquired events are consolidated to produce stable and specific associations. Initially, newly acquired information undergoes cellular consolidation in the hippocampus, which transiently supports the storage of recently acquired memories. In contrast, remote, or "old" memories are maintained in the cortex and show almost complete independence from the hippocampus. ⋯ First, localized nucleosomal histone variant exchange and histone modifications are integral for early stages of systems consolidation, whereas DNA methylation appears to be utilized to form stable marks that support memory maintenance. Since systems consolidation also requires discrete and time-sensitive changes in protein abundance, additional mechanisms, such as protein degradation, need also be considered, although their role in systems consolidation has yet to be investigated. Here, we discuss the role of molecular mechanisms in systems consolidation and their implications for understanding how memories persist over time.