Neuroscience
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Acquisition of a novel behavior induces higher levels of Arc mRNA than does overtrained performance.
Arc (also termed activity-regulated cytoskeleton-associated protein or Arg3.1), is an effector immediate early gene whose upregulation has been demonstrated during events of synaptic plasticity. In the present study, the possibility that Arc would be specifically upregulated in rats during the acquisition of a quickly learned behavioral task but not in overtrained animals was investigated. Three groups of rats, pseudotrained, newly trained and overtrained, were examined with respect to Arc expression following training on a simple operant lever-pressing task. ⋯ From these results we suggest that Arc is upregulated in an experience-dependent manner, with higher levels of induction occurring during the initial stage of learning. Furthermore, the finding of increased Arc levels in slow versus fast learners indicates that Arc expression may be associated with the length of time required to: (1) form new associations or (2) remodel existing connections. These results confirm other reports that Arc is a critical substrate for the synaptic plasticity underlying the acquisition of new behaviors.
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Interleukin-6 (IL-6) is a multifunctional cytokine that may have a role in energy regulation. Using a recombinant adeno-associated viral vector expressing murine interleukin-6 (rAAV-IL-6), we examined the chronic effects of centrally expressed IL-6 on food intake, body weight and adiposity in male Sprague-Dawley rats, and investigated the underlying mechanisms. Direct delivery of rAAV-IL-6 into rat hypothalamus suppressed weight gain and visceral adiposity without affecting food intake over a 5-week period. rAAV-IL-6 enhanced uncoupling protein 1 (UCP1) protein levels in interscapular brown adipose tissue (BAT). ⋯ These data demonstrate that chronic elevation of IL-6 in the CNS reduces body weight gain and visceral adiposity without affecting food intake. The mechanism involves sympathetic induction of UCP1 in BAT and, presumably, enhanced thermogenesis in BAT. Furthermore, chronic central IL-6 stimulation desensitizes IL-6 signal transduction characterized by reversal of elevated P-STAT3 levels.
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The identification of leptin and a range of novel anorectic and orexigenic peptides has focussed attention on the neural circuitry involved in the genesis of food intake and the reflex control of thermogenesis. Here, the neurotropic virus pseudorabies has been utilised in conjunction with the immunocytochemical localisation of a variety of neuroactive peptides and receptors to better define the pathways in the rat hypothalamus directed polysynaptically to the major thermogenic endpoint, brown adipose tissue. Infected neurones were detected initially in the stellate ganglion, then in the spinal cord followed by the appearance of third-order premotor neurones in the brainstem and hypothalamus. ⋯ Neurones in the retrochiasmatic nucleus and in the adjacent lateral arcuate nucleus which project to the brown adipose tissue express cocaine- and amphetamine-regulated transcript, pro-opiomelanocortin and leptin receptors. Neurones in the lateral hypothalamus, a site traditionally associated with the promotion of feeding, project to brown adipose tissue and large numbers of these contained melanin-concentrating hormone and orexin A and B. These data provide part of an anatomical framework which subserves the regulation of energy expenditure.
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Modulation of endogenous adenosine levels by inhibition of adenosine metabolism produces a peripheral antinociceptive effect in a neuropathic pain model. The present study used microdialysis to investigate the neuronal mechanisms modulating extracellular adenosine levels in the rat hind paw following tight ligation of the L5 and L6 spinal nerves. Subcutaneous injection of 50 microl saline into the nerve-injured paw induced a rapid and short-lasting increase in extracellular adenosine levels in the subcutaneous tissues of the rat hind paw ipsilateral to the nerve injury. ⋯ These results suggest that following nerve injury, peripheral capsaicin-sensitive primary sensory afferent nerve terminals are hypersensitive, and are able to release adenosine following a stimulus that does not normally evoke release in sham-operated or intact rats. Sympathetic postganglionic afferents do not appear to be involved in such release. The lack of effect on such release by the inhibitors of adenosine metabolism suggests an altered peripheral adenosine system following spinal nerve ligation.
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One of the essential requirements even in the most ancient life forms is to be able to preserve body fluid medium. In line with such requirement, animals need to perform different behaviors to cope with water shortages. As angiotensin II (ANGII) is involved on a widespread range of functions in vertebrates, including memory modulation, an integrative role, in response to an environmental water shortage, has been envisioned. ⋯ Moreover, nuclear brain NF-kappaB is activated by ANGII, and this effect is reversed by saralasin. Our results constitute the first demonstration in an invertebrate that cognitive functions are modulated by an environmental stimulus through a neuropeptide and give evolutionary support to the role of angiotensins in memory processes. Moreover, these results suggest that angiotensinergic system is preserved across evolution not only in its structure and molecular mechanisms, but also in its capability of coordinating specific adaptative responses.