Neuroscience
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Corneal afferent nerves project to two spatially distinct sites within the spinal trigeminal nucleus: the subnucleus interpolaris/caudalis transition and the subnucleus caudalis/upper cervical spinal cord transition. The role of these two regions in processing corneal input is uncertain. To determine if neurons in these regions encode different features of an applied corneal stimulus, immunoreactivity for the immediate early gene protein product, Fos, was quantified in barbiturate-anesthetized rats. ⋯ Double-labeling revealed that Fos immunoreactive neurons within the spinal trigeminal nucleus were restricted to regions densely labeled for calcitonin gene-related peptide. These results indicate that select features of corneal stimuli such as modality are encoded differently by neurons in the trigeminal subnucleus interpolaris/caudalis transition compared with those located in the subnucleus caudalis/cervical cord transition. It is likely that neurons in these two brainstem regions subserve different aspects of corneal sensation.
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Comparative Study
The serotonergic agent fluoxetine reduces neuropeptide Y levels and neuropeptide Y secretion in the hypothalamus of lean and obese rats.
Evidence suggests that serotonin and neuropeptide Y neurons in the hypothalamus, which respectively inhibit and stimulate food intake, may interact to control energy homoeostasis. We therefore investigated the effects of fluoxetine, which inhibits serotonin reuptake, on food intake and the activity of the neuropeptide Yergic arcuato-paraventricular projection in lean Wistar and Zucker rats. We also studied its effects in obese Zucker rats, in which obesity is postulated to be due to overactivity of the arcuato-paraventricular projection. ⋯ Furthermore, seven days fluoxetine treatment prevented the significant increases in hypothalamic neuropeptide Y messenger RNA which were induced in lean rats by food restriction which precisely matched the hypophagia induced by the drug. We conclude that fluoxetine inhibits various aspects of the activity of the neuropeptide Yergic arcuato-paraventricular neurons, and suggest that reduced neuropeptide Y release in the paraventricular nucleus may mediate, at least in part, the drug's hypophagic action. We further suggest that serotonin may influence food intake and energy balance by inhibiting the arcuato-paraventricular projection, and that the two neurotransmitters may act together to regulate feeding and energy homoeostasis.
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Systemic administration or local injection to the rat hindpaw of leukemia inhibitory factor induced a prolonged, dose dependent, mechanical hypersensitivity of the hindpaw flexion withdrawal reflex. Mechanical stimuli which were innocuous prior to leukemia inhibitory factor administration, evoked a rapid hindpaw withdrawal reflex indicative of mechanical allodynia. Pre-administration of anti-leukemia inhibitory factor antibodies prevented this behavioural hypersensitivity. ⋯ Anti-leukemia inhibitory factor had no effect upon hindpaw withdrawal thresholds when injected alone nor influenced the mechanical hypersensitivity produced by a subcutaneous injection of nerve growth factor. Injection of the closely related cytokine ciliary neurotrophic factor did not affect mechanical or thermal reflex withdrawal thresholds. Elevation of the neuroactive cytokine leukemia inhibitory factor following peripheral nerve injury may be a contributory factor to the pathogenesis of neuropathic pain.
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In the present study we demonstrate low level expression of the laminin alpha 2 chain in brain and localize the alpha 2 protein to the capillary basement membrane. While in peripheral basement membranes the laminin alpha 1 and alpha 2 chains have an almost mutually exclusive distribution, the present results suggest both alpha 1 and alpha 2 in the cerebral capillary basement membrane. ⋯ In contrast to the muscle and Schwann cell basement membrane, where alpha 2 deficiency causes structural basement membrane abnormalities, the present results show that the lack of the alpha 2 subunit in the cerebral capillary basement membrane is not detrimental to its structure. This observation might be explained by the fact that the cerebral capillary basement membrane expresses both alpha chains and therefore exhibits structural redundancy.
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There is general agreement that activation of the N-methyl-D-aspartate receptor is involved in thermal hyperalgesia. However, there is less agreement on the specific intracellular events subsequent to receptor activation and the involvement of other excitatory amino acid receptors in thermal hyperalgesia. In the present study, we found that the intrathecal administration of N-methyl-D-aspartate produced a dose- (1 fmol-1 pmol) and time-dependent thermal hyperalgesia. ⋯ Activation of AMPA, metabotropic or co-activation of AMPA and metabotropic glutamate receptors, at the doses tested, did not produce an acute thermal hyperalgesia. The thermal hyperalgesia produced by N-methyl-D-aspartate is mediated by activation of nitric oxide synthase and protein kinase C, but not by phospholipase C, phospholipase A2, cyclo-oxygenase or lipoxygenase. Collectively, the results are consistent with a role for spinal N-methyl-D-aspartate receptors, nitric oxide and protein kinase C in thermal hyperalgesia.