Neuroscience
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Apolipoprotein (APO, gene; apo, protein) D, a member of the lipocalin family, has been implicated in several, pathological conditions but neither its physiologic function(s) nor ligand(s) has been clearly identified so far. Presuming a role in nerve de- and regeneration, several groups investigated apoD alterations in Alzheimer's disease (AD). Reported data, however, were not unanimous. ⋯ No correlation was found to amyloid deposits. Brain samples with widespread NF changes showed significantly higher apoD than cases with low Braak stages. This increase, however, was restricted to the APOE epsilon3/3 group, whereas the APOE epsilon4 group did not show significant variations in hippocampal apoD.
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Choleratoxin B subunit-binding thick myelinated, A-fibre and unmyelinated, capsaicin-sensitive nociceptive C-fibre primary afferent fibres terminate in a strict topographic and somatotopic manner in the spinal cord dorsal horn. Injection of choleratoxin B subunit-horseradish peroxidase conjugate into injured but not intact peripheral nerves produced transganglionic labelling of primary afferents not only in the deeper layers (Rexed's laminae III-IV), but also in the substantia gelatinosa (Rexed's laminae II) of the spinal dorsal horn. This was interpreted in terms of a sprouting response of the Abeta-myelinated afferents and suggested a contribution to the pathogenesis of neuropathic pain [Nature 355 (1992) 75; J Comp Neurol 360 (1995) 121]. ⋯ In contrast, the proportion of labelled unmyelinated dorsal root axons relating to the transected, but not the intact nerves showed a significant, six-fold increase after sciatic nerve transection (intact: 4.9+/-1.3%; transected: 35+/-6.7%). These observations indicate that peripheral nerve lesion-induced transganglionic labelling of the substantia gelatinosa by choleratoxin B subunit-horseradish peroxidase may be primarily accounted for by the uptake and transganglionic transport of choleragenoid by injured capsaicin-sensitive C-fibre afferents rather than a sprouting response of A-fibre afferents. The present findings suggest an essential role of capsaicin-sensitive primary sensory neurons in lesion-induced spinal neuroplastic changes and provide further support for C-fibre nociceptor neurons being promising targets for the development of new strategies in pain management.
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Comparative Study
Estradiol inhibits atp-induced intracellular calcium concentration increase in dorsal root ganglia neurons.
Estrogen has been implicated in modulation of pain processing. Although this modulation occurs within the CNS, estrogen may also act on primary afferent neurons whose cell bodies are located within the dorsal root ganglia (DRG). Primary cultures of rat DRG neurons were loaded with Fura-2 and tested for ATP-induced changes in intracellular calcium concentration ([Ca(2+)](i)) by fluorescent ratio imaging. ⋯ Co-administration of these blockers with estrogen induced a further decrease of the ATP-induced [Ca(2+)](i) flux. Together, these results suggest that although ATP stimulation of P2X receptors activates L-, N-, and P-type VGCC, estradiol primarily blocks L-type VGCC. The estradiol regulation of this ATP-induced [Ca(2+)](i) transients suggests a mechanism through which estradiol may modulate nociceptive signaling in the peripheral nervous system.
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Intermittent hypoxia (IH) during sleep, a characteristic feature of sleep-disordered breathing (SDB) is associated with time-dependent apoptosis and spatial learning deficits in the adult rat. The mechanisms underlying such neurocognitive deficits remain unclear. Activation of the cAMP-response element binding protein (CREB) transcription factor mediates critical components of neuronal survival and memory consolidation in mammals. ⋯ Initial IH-induced impairments in spatial learning were followed by partial functional recovery starting at 14 days of IH exposure. We postulate that IH elicits time-dependent changes in CREB phosphorylation and nuclear binding that may account for decreased neuronal survival and spatial learning deficits in the adult rat. We suggest that CREB changes play an important role in the neurocognitive morbidity of SDB patients.
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Comparative Study
Immune rejection of a facial nerve xenograft does not prevent regeneration and the return of function: an experimental study.
Nerve grafts may be used to repair damaged peripheral nerves and also to facilitate spinal cord regeneration after experimental trauma. Little is known, however, about the possible use of xenografts and the role of immune rejection in the outcome of repair. ⋯ With longer (15-20 mm) transplants, however, restoration of eye closure becomes dependent on cyclosporine administration. Thus, in a situation where nerve repair does not occur without a graft, a host immune attack has an attritional effect which is not sufficient to prevent repair over short distances, but becomes obvious when the regenerating fibres have to cross longer segments of transplanted tissue.