Neuroscience
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The effect of treatment with a broad-spectrum inhibitor (BB1101) of the matrix metalloproteinases (MMPs) on nerve regeneration and functional recovery after nerve crush was examined. Drug treatment had no effect on latency but from 63 days the compound muscle action potential was significantly increased and was no different to that in the sham-operated controls at 72 days. Levels of MMP mRNA expression, and the localisation and activity of MMP proteins, were examined in rats for a 2 month period following a nerve crush injury, and compared with sham-operated controls. ⋯ Regenerating axons showed immunoreactivity for MMP-2 and MMP-3. In situ zymography confirmed that the activity of MMPs in the nerve was increased following crush but that the activity was greatly reduced in rats treated with BB-1101. Thus despite the inhibition of MMPs by BB-1101, the drug did not appear to essentially affect nerve degeneration or regeneration following nerve crush but that it could be beneficial in promoting the more effective reinnervation of muscles possibly by actions at the level of the muscles.
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Interactions between cannabinoid and opioid systems have been implicated in reward and drug seeking behaviors involving neuronal circuitry in the nucleus accumbens (Acb) shell and core. To determine the relevant sites, we examined the electron microscopic localization of cannabinoid type-1 (CB1) receptors and mu-opioid receptors in each Acb compartment in rat brain. CB1 receptor immunogold labeling was seen on the plasma membrane and within the cytoplasm of neuronal and glial profiles throughout the Acb. ⋯ Conversely, of the synaptic mu-labeled terminals, 20% in the shell and 10% in the core contacted dendrites containing CB1 receptors. These findings provide ultrastructural evidence that cannabinoid-opioid interactions are mediated by activation of CB1 and mu-opioid receptors within the same or synaptically linked neurons in the Acb shell and core. They also suggest a particularly important role for presynaptic CB1 receptors in the reward circuit of the Acb shell.
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Comparative Study
The ventral hippocampal regulation of prepulse inhibition and its disruption by apomorphine in rats are not mediated via the fornix.
Prepulse inhibition (PPI) of startle is a measure of sensorimotor gating that is impaired in schizophrenia. We have reported that PPI is regulated by the ventral hippocampus (VH) and that the PPI disruptive effects of the dopamine agonist apomorphine are enhanced 4 weeks after excitotoxic lesions of the VH. The mechanisms responsible for the VH influence on PPI are not understood, but have been ascribed to interactions between the VH and nucleus accumbens. ⋯ The PPI-disruptive effects of apomorphine were significantly enhanced by excitotoxic or electrolytic lesions of the VH, but not by fornix transection. The influence of the VH on PPI and its dopaminergic regulation does not appear to be mediated via the fornix. The enhanced sensitivity to the PPI-disruptive effects of apomorphine after VH lesions is not dependent on excitotoxin-induced changes in the VH or its downstream projections.
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Small-diameter sensory neurons are key contributors in joint pain and have been implicated in the pathogenesis of rheumatoid arthritis (RA). Small-diameter sensory neurons can be separated into at least two distinct populations, which include isolectin B4 (IB4)-binding and tyrosine receptor kinase (trk) A-expressing. While trkA-expressing neurons have been identified in the rat knee joint there are no data, we are aware of, to suggest that IB4-binding neurons are also present. ⋯ Injection of FG into skin over the medial aspect of the rat knee (n=3) showed 48% of these cutaneous afferents in L3 and L4 DRG were double-labeled with FG and FITC. A complete absence of IB4-binding neurons in the rat knee joint makes it unlikely that this predominantly cutaneous, IB4-binding population of afferent neurons could have any significant influence in chronic inflammatory joint disease. This suggests that trkA-expressing neurons are the sole population of small-diameter sensory neurons in the knee joint and implies a significant role for these afferents in the progression of RA.
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The cortical regions surrounding the suprasylvian sulcus have previously been associated with motion processing. Of the six areas originally described by Palmer et al. [J Comp Neurol 177 (1978) 237], the posteromedial lateral suprasylvian (PMLS) cortex has attracted the greatest attention. Very little physiological information is available concerning other suprasylvian visual areas, and in particular, the anteromedial lateral suprasylvian cortex (AMLS). ⋯ Finally, 45% of 20 neurons were direction selective to a radial optic flow stimulus. Overall, these results suggest that AMLS cortex is involved in higher-order analyses of visual motion. It is possible that the AMLS cortex represents a region between PMLS and the anterior ectosylvian visual area in a functional hierarchy of areas involved in motion integration.