Neuroscience
-
Intraperitoneal injection of the endotoxin lipopolysaccharide produces an inflammation accompanied by immune system activation and secretion of cytokines that stimulate the hypothalamo-pituitary-adrenal (HPA) axis to release the anti-inflammatory corticosterone. Upstream in HPA axis are neuroendocrine corticotropin-releasing hormone neurons in the paraventricular nucleus whose multipeptidergic phenotype changes during inflammation: coexisting corticotropin-releasing hormone and cholecystokinin mRNAs are up-regulated whereas neurotensin mRNA expression is induced de novo. These changes may be mediated by prostaglandins released from perivascular and microglial cells in response to circulating cytokines. ⋯ Because indomethacin also elevated circulating corticosterone, animals were adrenalectomized and corticosterone replaced. Results showed that i.p. indomethacin administration suppressed lipopolysaccharide effects in a phenotype non-specific manner: one injection was sufficient to prevent both the increase in corticotropin-releasing hormone and cholecystokinin mRNAs expression and the induction of neurotensin mRNA expression. Therefore, neuroendocrine corticotropin-releasing hormone neurons with different peptidergic phenotypes appear to respond as a whole in the acute phase response to systemic infection.
-
The expression and functional responses of P2X receptors in bladder and cutaneous sensory neurons of adult rats and mice have been studied using immunohistochemistry and patch clamp techniques. Cell bodies of bladder pelvic afferents were identified in L6 and S1 dorsal root ganglia (DRG), following Fast Blue injection into the muscle wall of the urinary bladder. Similarly, cutaneous sensory neurons were identified in L3 and L4 DRG, following Fast Blue injection into the saphenous nerve innervating the skin. ⋯ The remaining bladder sensory neurons demonstrated biphasic, transient or no response to P2X agonists. In contrast, only 24% of cutaneous afferent neurons gave persistent currents to alpha beta meATP (30 microM), with 66% of cells giving transient or biphasic currents and the remaining 10% being non-responsive. Our results suggest that, in contrast to DRG neurons in general, bladder sensory neurons projecting via pelvic nerves express predominantly P2X(2/3) heteromeric receptors, which are likely to mediate the important roles of ATP as a signaling molecule of urinary bladder filling and nociception.
-
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.
-
Comparative Study
Connective tissue growth factor: a novel marker of layer VII neurons in the rat cerebral cortex.
Connective tissue growth factor (CTGF) belongs to a family of secreted, extracellular matrix-associated proteins that are involved in the regulation of cellular functions such as adhesion, migration, mitogenesis, differentiation and survival. Recent studies have also suggested the up-regulation of CTGF in response to trauma, scar formation and excitotoxicity in the CNS. To further elucidate the localization and regulation of this molecule in the rat brain we performed in situ hybridization experiments and found a very strong and selective expression of CTGF messenger ribonucleic acid (mRNA) on the band of layer VII neurons throughout the adult cerebral cortex. ⋯ Interestingly, injury experiments using direct cerebral trauma or injection of excitotoxic kainic acid into rat brain failed to up-regulate CTGF mRNA after injury and during the ensuing period of neuronal cell death, gliosis and neural scar tissue formation. Altogether, the current data suggest a constitutive role of CTGF, particularly in the adult cerebral cortex. In view of the strong ascending projections of subplate neurons into cortical layer 1, this molecule may be involved in the modulation of synaptic input to apical dendrites of pyramidal neurons.
-
We describe the thorough characterisation of a new transgenic mouse line overexpressing the 695-amino acid isoform of human amyloid precursor protein harbouring the Swedish double familial Alzheimer's disease mutation. This line, referred to as TAS10, exhibits neuropathological features and cognitive deficits that are closely correlated to the accumulation of Abeta in their brain and that are reminiscent of those observed in AD. ⋯ Morphometric studies demonstrate that the synapse to neuron ratio is higher in transgenics than in control mice at 12 months, but this ratio decreases as they age and synapse size increases. Thus, this mouse model exhibits a close correlation of amyloid burden with behavioural deficits and ultrastructural abnormalities and so represents an ideal system to study the mechanisms underlying the impact of amyloid pathology on CNS function.