Current opinion in neurobiology
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Curr. Opin. Neurobiol. · Aug 2010
Microglia-neuronal signalling in neuropathic pain hypersensitivity 2.0.
Microglia are increasingly recognized as critical in the pathogenesis of pain hypersensitivity caused by injury to peripheral nerves. The core signalling pathway is through P2X4 purinergic receptors on the microglia which, via the release of brain-derived neurotrophic factor, cause disinhibition of nociceptive dorsal horn neurons by raising intracellular chloride levels. ⋯ There is increased discharge output, unmasking of responses to innocuous peripheral inputs and spontaneous activity in neurons that otherwise only signal nociception. Together the changes caused by microglia-neuron signalling may account for the main symptoms of neuropathic pain in humans.
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Curr. Opin. Neurobiol. · Aug 2010
The prevalence of epigenetic mechanisms in the regulation of cognitive functions and behaviour.
A complex interplay between the pattern of DNA methylation and a large and growing number of post-translational modifications (PTMs) of histones contribute to the epigenetic regulation of gene transcription. This epigenetic regulation involves histone acetylation, phosphorylation and methylation, and is now known to be important for several forms and phases of long-term memory. ⋯ The epigenetic mechanisms that contribute to these deficits include: first, the dysregulation of key components of the epigenetic machinery; second, alterations in the expression of genes important for cognition and behaviour by epigenetic mechanisms; third, instability at trinucleotide repeats; and fourth, the breakdown of major epigenetic processes like imprinting and X-chromosome inactivation. Thus, both pharmacological and environmental interventions that act on epigenetic mechanisms provide a promising tool for the treatment of a wide variety of cognitive and behavioural disorders.
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By forming close contacts with synapses, astrocytes secrete neuroactive substances and remove neurotransmitters, thus influencing the processing of information by the nervous system. Here, we review recent work on astrocytes and their roles in regulating neuronal function and synaptic plasticity. ⋯ They also provide a link between neurons and the vasculature, potentially changing the cerebral microcirculation. Recent work has provided insights into the relative contributions of specific astrocytic cues and transporters to synaptic transmission, plasticity, and animal behavior.