Brain research
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Comparative Study
Urocortin 2 increases c-Fos expression in topographically organized subpopulations of serotonergic neurons in the rat dorsal raphe nucleus.
Corticotropin-releasing factor (CRF)-related peptides modulate stress-related physiology and behavior. Some of the physiological and behavioral effects of CRF-related peptides may be due to actions on CRF type 2 (CRF2) receptors modulating serotonergic systems in the dorsal raphe nucleus (DR). To determine if CRF2 receptor activation has effects on serotonergic neurons in the DR in conscious behaving rats, we gave intracerebroventricular (icv) injections of the selective CRF2 receptor agonist urocortin 2 (0, 0.01, 0.1, or 1.0 mug in 2 microl saline) to adult male Wistar rats and quantified c-Fos expression in topographically organized subpopulations of serotonergic neurons within the DR. ⋯ Urocortin 2, in the absence of any effects on most behavioral endpoints studied, consistently increased c-Fos expression in subpopulations of serotonergic neurons identified by either tryptophan hydroxylase or serotonin immunostaining within specific subdivisions of the DR, particularly the dorsal region of the mid-rostrocaudal and caudal DR (-7.64, -8.18, -8.54, and -9.16 mm bregma). These studies demonstrate that urocortin 2 has selective actions on a subset of DR serotonergic neurons. Urocortin 2 actions on serotonergic systems described here may contribute to delayed behavioral effects of urocortin 2 described previously, including orexigenic, locomotor, and anxiety-related effects in a variety of behavioral tests as well as potentiation of conditioned fear and induction of escape deficits in a model of learned helplessness.
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Comparative Study
Sleep disturbances in the rotenone animal model of Parkinson disease.
Parkinson disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the presence of intracytoplasmatic inclusions known as Lewy bodies. Chronic administration of rotenone (RT) produces Parkinson's-like symptoms in rats. Because PD patients have disrupted sleep patterns, we determined if chronic RT administration produces similar changes in rat sleep. ⋯ Dopaminergic cell damage persisted in the L-dopa-RT-infused rats. We conclude that the RT-PD rat model is associated with large long-term sleep disruption, however, the vehicle, DMSO/PEG had as large an effect as RT on sleep, thus changes in sleep cannot be ascribed to loss of dopaminergic cells. Such results question the validity of the RT-PD rat model.
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Comparative Study
The effect of endoneurial nerve growth factor on calcitonin gene-related peptide expression in primary sensory neurons.
Recent findings indicate that calcitonin gene-related peptide (CGRP) is involved in neuropathic pain, this peptide being up-regulated in a small population of large- and medium-sized primary sensory neurons after peripheral nerve injury. In adult animals, the expression of CGRP is regulated by nerve growth factor (NGF). After nerve injury, NGF is up-regulated at the injury site for several weeks, and this up-regulation contributes to the onset of neuropathic pain. ⋯ The injection of vehicle did not produce any change on CGRP expression in primary sensory neurons. These results suggest that endoneurial NGF is responsible for the increase in CGRP expression in some large-sized neurons and their central processes observed after nerve injury in animal models of neuropathic pain. Our findings contribute to the understanding of the role of NGF in neuropathic pain.
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Comparative Study
Effect of systemic and intrathecal gabapentin on allodynia in a new rat model of postherpetic neuralgia.
Patients with postherpetic neuralgia often have an increased sensitivity to a tactile stimulus but impaired thermal sensitivity in the same affected dermatomes. We recently found that depletion of capsaicin-sensitive afferents by systemic treatment with a potent TRPV1 agonist, resiniferotoxin, in adult rats produces long-lasting paradoxical changes in mechanical and thermal sensitivities, which resemble the unique clinical features of postherpetic neuralgia. The anticonvulsant gabapentin is effective in reducing the subjective pain score in patients with postherpetic neuralgia. ⋯ Intraperitoneal injection of 30-60 mg/kg of gabapentin in resiniferotoxin-treated rats significantly increased the withdrawal threshold in response to von Frey filaments. Furthermore, intrathecal administration of 10-30 microg of gabapentin also produced a significant effect on the mechanical withdrawal threshold in all resiniferotoxin-treated rats. These data provide complementary new information that gabapentin administered systemically and spinally can effectively relieve tactile allodynia in this animal model of postherpetic neuralgia.
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Traumatic brain injury produces peroxynitrite, a powerful oxidant which triggers DNA strand breaks, leading to the activation of poly(ADP-ribose)polymerase-1 (PARP-1). We previously demonstrated that 3-aminobenzamide, a PARP inhibitor, is neuroprotective in a model of traumatic brain injury induced by fluid percussion in rat, suggesting that PARP-1 could be a therapeutic target. ⋯ These neurological recovery-promoting effects are associated with the inhibition of PARP-1 activation caused by trauma, as demonstrated by abolishment of immunostaining of poly(ADP-ribose). Thus, the present work strengthens strongly the concept that PARP-1 inhibition may be a suitable approach for the treatment of brain trauma.