Trends in neurosciences
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Trends in neurosciences · Feb 2005
ReviewNeuropathic pain and spinal microglia: a big problem from molecules in "small" glia.
Neuropathic pain is a common and severely disabling state that affects millions of people worldwide. Such pain can be experienced after nerve injury or as part of diseases that affect peripheral nerve function, such as diabetes and AIDS; it can also be a component of pain in other conditions, such as cancer. ⋯ It is important to establish how these molecules are activated in spinal microglia following nerve injury and how they cause signaling to neurons in the dorsal horn pain transmission network. Answers to these questions could lead to new strategies that assist in the diagnosis and management of neuropathic pain--strategies not previously anticipated by a neuron-centric view of pain plasticity in the dorsal horn.
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Trends in neurosciences · Oct 2004
ReviewThe aging brain: morphomolecular senescence of cortical circuits.
The human brain is uniquely powerful with respect to cognitive abilities, yet the hippocampal and neocortical circuits that mediate such complex functions are highly vulnerable to aging. Their selective vulnerability is profoundly manifested in Alzheimer's disease (AD), where degeneration of select neurons leads to a near complete loss of cognitive abilities. Most of us will avoid AD as we age. ⋯ Animal studies suggest that both AD and age-associated cognitive impairment reflect vulnerability of the same circuits. However, neuron death predominates in the former, whereas the latter is probably mediated by synaptic alterations in otherwise intact circuits. Fortunately, such age-related synaptic alterations could be reversible, as suggested by recent studies of hormone replacement.
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Trends in neurosciences · Nov 2003
ReviewNeuromelanin of the substantia nigra: a neuronal black hole with protective and toxic characteristics.
Neuromelanin accumulates in dopaminergic neurons during normal aging, and in Parkinson's disease, neurons with this pigment are those that selectively degenerate. Intraneuronal neuromelanin could play a protective role during its synthesis by preventing the toxic accumulation of cytosolic catechol derivatives and, in addition, by its ability to scavenge reactive metals, pesticides and other toxins to form stable adducts. However, dying neurons in Parkinson's disease that release neuromelanin might induce a vicious cycle of chronic neuroinflammation and neuronal loss.
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Trends in neurosciences · Apr 2003
ReviewThe Nogo-66 receptor: focusing myelin inhibition of axon regeneration.
CNS myelin inhibits axonal outgrowth in vitro and is one of several obstacles to functional recovery following spinal cord injury. Central to our current understanding of myelin-mediated inhibition are the membrane protein Nogo and the Nogo-66 receptor (NgR). ⋯ Additional studies have identified a potential coreceptor for NgR as p75(NTR), and a second-messenger pathway involving RhoA that inhibits neurite elongation. Although these findings expand our understanding of the molecular determinants of adult CNS axonal regrowth, the physiological roles of myelin-associated inhibitors in the intact adult CNS remain ill-defined.
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The biochemical bases of the placebo effect are still incompletely known. We show here that the placebo effect in Parkinson's disease is due, at least in part, to the release of dopamine in the striatum. ⋯ According to this theory, brain dopamine release could be a common biochemical substrate for the placebo effect encountered in other medical conditions, such as pain and depression. Other neurotransmitters or neuropeptides, however, are also likely to be involved in mediating the placebo effect (e.g. opioids in pain disorders, serotonin in depression).