Neuroscience
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Vagal afferents ascending from the gastrointestinal tract synapse on neurons in the nucleus of the solitary tract. Although these neurons constitute a significant proportion of solitary tract cells their firing behaviour and synaptic properties are not documented. Since gastrointestinal tract afferent termination sites overlap with regions mediating cardiorespiratory reflexes the possibility of convergence with afferents mediating cardiovascular and respiratory reflexes was proposed. ⋯ We conclude that solitary tract neurons receiving signals from the sub-diaphragmatic vagus nerves (most likely from gastrointestinal tract structures) appear to be a distinct pool of neurons. There was a heterogeneity in terms of both their ongoing activity and projection targets but despite this, there were three consistent properties. First, sub-diaphragmatic vagus nerve evoked predominantly excitatory synaptic responses in solitary tract neurons; second, neurons exhibited lasting paired pulse depression following activation of sub-diaphragmatic vagus nerves; and third, sub-diaphragmatic vagus nerve-driven solitary tract neurons were
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Brain-derived neurotrophic factor, the most abundant of the neurotrophins in the brain, enhances the growth and maintenance of several neuronal systems, serves as a neurotransmitter modulator, and participates in use-dependent plasticity mechanisms such as long-term potentiation and learning. In recent years, evidence has been gathering that brain-derived neurotrophic factor may have an important role in the neuropathology and treatment of depression. It has recently been reported that chronic (at least two weeks) antidepressant treatment leads to an up-regulation of brain-derived neurotrophic factor messenger RNA levels in the hippocampus, an important brain area for behavioral regulation, as well as learning and memory. ⋯ In this report, we have tested the hypothesis that the combination of these two interventions, general physical activity and antidepressant treatment, leads to increased levels of specific promoter-derived transcripts of brain-derived neurotrophic factor messenger RNA in a manner that appears to be both additive and accelerated. Our results suggest that these two very different interventions may possibly converge at the cellular level. The induction of brain-derived neurotrophic factor expression by activity/pharmacological treatment combinations could represent an important intervention for further study, to potentially improve depression treatment and management.
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The aim of this investigation was to determine whether murine models of inflammatory, neuropathic and cancer pain are each characterized by a unique set of neurochemical changes in the spinal cord and sensory neurons. All models were generated in C3H/HeJ mice and hyperalgesia and allodynia behaviorally characterized. A variety of neurochemical markers that have been implicated in the generation and maintenance of chronic pain were then examined in spinal cord and primary afferent neurons. ⋯ However, in this cancer-pain model, changes including massive astrocyte hypertrophy without neuronal loss, increase in the neuronal expression of c-Fos, and increase in the number of dynorphin-immunoreactive neurons were observed in the spinal cord, ipsilateral to the limb with cancer. These results indicate that a unique set of neurochemical changes occur with inflammatory, neuropathic and cancer pain in C3H/HeJ mice and further suggest that cancer induces a unique persistent pain state. Determining whether these neurochemical changes are involved in the generation and maintenance of each type of persistent pain may provide insight into the mechanisms that underlie each of these pain states.
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Single unmyelinated axons in the superficial branch of the peroneal nerve of human subjects were recorded (microneurography) and the response patterns during tonic pressure stimulation (14N at 30 mm(2); 120 s) were assessed using the previously described "marking technique". It was found that tonic pressure stimuli induced augmenting pain responses which were matched by the discharges of initially mechano-insensitive ("silent") C-units, whereas mechano- and heat-responsive "polymodal" C-nociceptors showed a response pattern incompatible with the stimulus-induced perceptions, namely strong initial excitation, followed by adaptation. Eighteen mechano- and heat-responsive "polymodal" C-fibers and 11 mechano-insensitive units were studied. ⋯ A second, identical pressure stimulus induced a stronger response in mechano-insensitive and a weaker response in mechano-responsive units. The stronger response, indicating sensitization, matched the more intense pain perception during the second pressure stimulus. It is concluded that mechano-insensitive C-nociceptors encode pressure-induced pain in human hairy skin and that they play an important role in static mechanical hyperalgesia.
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In the symptomatic treatment of mild to moderately severe dementia associated with Alzheimer's disease, donepezil (E2020) has been introduced for the inhibition of acetylcholinesterase activity in the human brain. However, there is no morphological evidence as to how this chemical agent affects the acetylcholinesterase-positive structures in the various areas of the human and the rat CNS. This study demonstrates by histochemical means that donepezil exerts a dose-dependent inhibitory effect in vitro on acetylcholinesterase activity. ⋯ These histochemical results provide the first morphological evidence that, under in vitro circumstances, donepezil is not a general acetylcholinesterase inhibitor in the CNS, but rather selectively affects the different brain areas and, within these, the cholinoceptive and cholinergic structures. The acetylcholinesterase staining in the nerve fibers (innervating the intracerebral blood vessels of the human brain and the extracerebral blood vessels of the rat brain) and at the neuromuscular junction in the diaphragm and gastrocnemius muscle of rat, was also inhibited dose dependently by donepezil. It is concluded that donepezil may be a valuable tool with which to influence both the pre- and the postsynaptic acetylcholinesterase-positive structures in the human and rat central and peripheral nervous systems.