Neuroscience
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Comparative Study
The distribution of gamma-hydroxybutyrate-induced Fos expression in rat brain: comparison with baclofen.
gamma-Hydroxybutyrate (GHB) is a euphoric, prosocial and sleep inducing drug that binds with high affinity to its own GHB receptor site and also more weakly to GABA(B) receptors. GHB is efficacious in the treatment of narcolepsy and alcoholism, but heavy use can lead to dependence and withdrawal. Many effects of GHB (sedation, hypothermia, catalepsy) are mimicked by GABA(B) receptor agonists (e.g. baclofen). ⋯ Surprisingly, Fos immunoreactivity was not observed with either GHB or baclofen in reward-relevant regions such as the nucleus accumbens, striatum and ventral tegmental area. Overall these results indicate a distinctive signature of brain activation with GHB that may be only partly due to GABA(B) receptor effects. This confirms a unique neuropharmacological profile for GHB and indicates key neural substrates that may underlie its characteristic influence on sleep, body temperature, sociability and endocrine function.
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Cadherin23 has been proposed to form the upper part of the tip link, an interstereocilial link believed to control opening of transducer channels of sensory hair cells. However, we detect tip link-like links in mouse mutants with null alleles of Cdh23, suggesting the presence of other components that permit formation of a link between the tip of one stereocilium and the side of the adjacent taller stereocilium.
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The somatotopic map of the first nociceptive component in the primary somatosensory cortex (S1) is still unclear. In this study, a CO(2) laser was applied to the tail of the rat to induce nociception without the interference from large myelinated (A(beta)) fibers. Thus, only noxious fibers could be activated. ⋯ We found that whether light touch or laser-induced nociception was applied to the tail of the rat, the responsive topography in S1 was consistent. Discrimination of these two modalities was achieved vertically in the same column; the deeper layer represented the nociceptive response while the superficial layer encoded the response to light touch. This is quite different from that of a primate brain.
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During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of cerebrospinal fluid (CSF) production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the small inducible cytokine A2 (SCYA2) gene which codes for monocyte chemoattractant protein-1 (MCP-1). ⋯ Given that we also detected increased levels of MCP-1 protein by ELISA, we sought to identify potential downstream targets of MCP-1 and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding endothelial leukocyte adhesion molecule 1 (E-selectin), a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during peripheral tissue inflammation, likely initiated by blood-borne inflammatory mediators, which may modify events in CNS.
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Experiential therapies, such as enriched environment (EE), have been shown to influence the neurodegenerative processes that underlie Parkinson's disease. We have previously demonstrated that EE promotes functional improvement in dopamine-depleted rats. Here we compare the influence of exposure to EE prior to versus after dopamine depletion in the 6-hydroxydopamine rat model of Parkinson's disease. ⋯ Exposure to pre-lesion EE in particular promoted structural plasticity as indicated by increased expression of the main cytoskeletal component microtubule associated protein-2 in the lesion dorsal striatum. Continuous EE showed absence of rotational bias suggesting attenuated dopamine loss. These data indicate that enriched lifestyle before the onset of motor symptoms and rehabilitation programs after diagnosis might be beneficial in patients with Parkinson's disease.