Neuroscience
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Comparative Study
Differential neuronal activation in the hypothalamic paraventricular nucleus and autonomic/neuroendocrine responses to I.C.V. endotoxin.
The paraventricular nucleus (PVN) of the hypothalamus is a key site for regulating neuroendocrine and autonomic activities. To study the role of the PVN activation in brain inflammation-induced autonomic/endocrine responses, lipopolysaccharide (LPS; 0.5 or 5 microg) was administered i.c.v. and rats were killed 1, 3 or 6 h after the injection. I.c.v. ⋯ Activation of the PVN by i.c.v. LPS likely occurs through both central and systemic routes. Differential neuronal activation in the PVN is functionally related to autonomic/endocrine responses elicited by brain inflammation.
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Comparative Study
Vestibulo-oculomotor behaviour in rats following a transient unilateral vestibular loss induced by lidocaine.
The effects of a transient vestibular nerve blockade, achieved by intra-tympanic instillation of lidocaine, were studied in rats by recording horizontal eye movements in darkness. Evaluation of the dose-response relationship showed that a maximal effect was attained with a concentration of 4% lidocaine. Within 15 min of lidocaine instillation, a vigorous spontaneous nystagmus was observed which reached maximal frequency and velocity of the slow phase after about 20 min. ⋯ The same effect has previously been demonstrated in both short- (days) and long-term (months) compensated rats, by antagonising the GABA(B) receptor. In summary, this study provides the first observations of vestibulo-oculomotor disturbances during the first hour after a rapid and transient unilateral vestibular loss in the rat. By using this method, it is possible to study immediate behavioural consequences and possible neural changes that might outlast the nerve blockade.
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Painful peripheral neuropathy is a major dose-limiting adverse effect of many cancer chemotherapeutic agents, such as the vinca alkaloids and taxanes. Recent studies demonstrate sexual dimorphism in second-messenger signaling for primary afferent nociceptor sensitization, and a role of second messengers in the models of metabolic and toxic painful peripheral neuropathies. This study tested the hypothesis that sexual dimorphism alters the severity and second-messenger signaling pathways for enhanced nociception in an animal model of vincristine-induced painful peripheral neuropathy. ⋯ Inhibition of protein kinase C epsilon (PKC epsilon ) attenuated vincristine-induced hyperalgesia in males and ovariectomized females, but not in normal females or in estrogen-replaced ovariectomized females. Inhibitors of protein kinase A, protein kinase G, p42 / p44-mitogen activated protein kinase and nitric oxide synthase also attenuated vincristine-induced hyperalgesia, but to a similar degree in both sexes. These data demonstrate an estrogen-dependent sexual dimorphism in vincristine-induced hyperalgesia (female>male) and an unexpected opposite sexual dimorphism in the contribution of PKC epsilon to the severity of this hyperalgesia (male>female).
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To examine the role of GABA in the respiratory rhythm and pattern generation in neonatal mice, we analyzed the function of the respiratory control system of 67-kDa isoform of glutamic acid decarboxylase (GAD67)-deficient neonatal mice. In these mutant (GAD67-/-) mice, GABA levels in the brainstem were reduced to about 30% of those in wild-type (GAD67+/+) mice. In in vivo preparations, ventilatory parameters were analyzed by whole body plethysmography and electromyography of intercostal muscles. ⋯ Superfusion of the in vitro GAD67-/- preparation with 10 microM GABA prolonged C4 burst duration and partly restored a normal pattern of inspiration, although the restoration was limited. These results indicate that reduced GABA levels during the perinatal period induce malfunction in the respiratory control system. We suggest that GABAergic transmission is not essential for basic respiratory rhythm generation but plays an important role in the maintenance of regular respiratory rhythm and normal inspiratory pattern in neonatal mice.
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Glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN) and their receptors (GFRalpha1, GFRalpha2 and Ret) play an important role in the survival of neurons in the central and peripheral nervous system. For example, GDNF as well as other trophic factors promotes photoreceptor survival during retinal degeneration. Recent studies have proposed that part of neurotophic rescue of photoreceptors may be indirect, mediated by interaction of the neurotrophic factors with other cell types, that in turn release secondary factors that act directly on photoreceptors. ⋯ Exogenous GDNF increased brain-derived neurotrophic factor, basic fibroblast growth factor and GDNF, but not NTN mRNA production. On the other hand, NTN increased NTN, but not GDNF mRNA production in cultured Müller cells. These observations suggest that GDNF, NTN and their receptors are involved in the regulation of trophic factor production in retinal glial cells, and that functional glia-neuron network may utilize GDNF family for the protection of neural cells during retinal degeneration.