Neuroscience
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Following 2 weeks acclimation to the running wheel in the home cages, an i.p. injection of a synthetic double-stranded RNA, polyriboinosinic:polyribocytidylic acid (poly I:C, 3 mg/kg), was performed to produce the immunologically induced fatigue in rats. The daily amounts of spontaneous running wheel activity decreased to about 40-60% of the preinjection level until day 9 with normal circadian rhythm, then gradually returned to the baseline level by day 14. Rats given a heat exposure (36 degrees C for 1 h) for the consecutive 3 days showed an increase in activity except for the first day. ⋯ Quantitative analysis of mRNA levels using a real-time capillary reverse transcriptase-polymerase chain reaction (RT-PCR) method revealed that interferon-alpha (IFN-alpha) mRNA contents in the cortex, hippocampus, hypothalamic medial preoptic, paraventricular, and ventromedial nuclei were higher in the poly I:C group than those in the saline and heat-exposed groups on day 7, although the amount of interleukin-1 beta mRNA showed no differences. Serum adrenocorticotropic hormone and catecholamine levels were not significantly different between groups. The present results indicate that the prolonged fatigue induced by poly I:C, which is evaluated by the spontaneous running wheel activity, can be used as an animal model for the immunologically induced fatigue associated with viral infection, and suggest that brain IFN-alpha may play a role in this model.
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Orexins (OXs) regulate sleep with possible interactions with brain noradrenergic neurons. In addition, noradrenergic activity affects barbiturate anesthesia. As we have also recently reported that OXs selectively evoke norepinephrine release from rat cerebrocortical slices we hypothesized that barbiturate anesthesia may result from of an interaction with central orexinergic systems. ⋯ A GABAA antagonist, bicuculline, did not modify the inhibitory effects of thiopental and the GABAA agonist, muscimol, did not inhibit norepinephrine release. In addition there was no interaction of barbiturates with either OX1 or OX2 receptors. Collectively our data suggest that orexinergic neurons may be an important target for barbiturates, and GABAA, OX1 and OX2 receptors may not be involved in this interaction.
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The neurochemistry of aggression and rage has largely focused on the roles played by neurotransmitters and their receptor mechanisms. In contrast, little attention has been given to the possible functions of other substances. Interleukin-1beta is an immune and brain-derived cytokine that is present in the hypothalamus. ⋯ In the third experiment, pretreatment with a selective 5-HT2 receptor antagonist, LY-53857, blocked the facilitating effects of interleukin-1beta upon defensive rage. These findings reveal for the first time that brain cytokines can dramatically alter aggressive behavior. In particular, interleukin-1beta in the medial hypothalamus potentiates defensive rage behavior elicited from the periaqueductal gray in the cat, and the potentiating effects of interleukin-1beta on this form of emotional behavior are mediated via a 5-HT2 receptor mechanism.
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Focal traumatic injury to the cerebral cortex is associated with early activation of the neuronal isoform of nitric oxide synthase (nNOS), where high concentrations of nitric oxide-derived free radicals elicit extensive DNA damage. Subsequent activation of the nuclear repair enzyme poly(ADP-ribose) polymerase (PARP) causes a severe energy deficit leading to the ultimate demise of affected neurons. Little is known about the temporal relationship of nNOS and PARP activation and the neuroprotective efficacy of their selective blockade in traumatic brain injury. ⋯ In contrast, i.p. AB treatment remained largely ineffective. In conclusion, our data indicate early activation of PARP after cold lesion that is, at least in part, related to nNOS induction and supports the relevance of nNOS and/or PARP inhibition to therapeutic approaches of traumatic brain injury.
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We utilized morphometric analysis of 3 day cultures of hippocampal neurons to determine the effects of both estradiol and the synthetic estrogen receptor modulator raloxifene on several parameters of neuronal growth and differentiation. These measurements included survival, neurite production, dendrite number, and axon and dendrite length and branching. 17 beta-Estradiol (10 nM) selectively stimulated dendrite branching; this effect was neither mimicked by alpha-estradiol, nor blocked by the estrogen receptor antagonist ICI 182780. The selective estrogen receptor modulator raloxifene (100 nM) neither mimicked nor reversed the effects of estradiol on dendritic branching. ⋯ These data support the hypothesis that 17 beta-estradiol is acting via alpha estrogen receptors in influencing hippocampal development in vitro. Raloxifene, prescribed to combat osteoporosis in post-menopausal women, is a selective estrogen receptor modulator with tissue-specific agonist/antagonist properties. Because raloxifene had no effect on dendritic branching, we hypothesize that it does not interact with the alpha estrogen receptor in this experimental paradigm.