Neuroscience
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Although there has been growing interest in the neuroanatomical and physiological mechanisms underlying aggressive behavior, little work has focused on possible mechanisms controlling natural plasticity in aggression. In the current study, we used naturally occurring changes in aggression level displayed by female Peromyscus californicus across the estrous cycle and parallel changes in c-fos expression to examine possible brain regions involved in mediating this plasticity. We found that c-fos expression was increased in females exposed to a conspecific female intruder compared with control females in numerous brain regions thought to be involved in the control of aggression. ⋯ Conversely, c-fos increased in the medial amygdala (MeA) across all stages of estrus compared with controls, suggesting the MeA is not involved in mediating changes in individual levels of aggression. Moreover, we found correlations between several measures of aggression and c-fos expression in the BNST and LSv but not the MeA, again suggesting a role in mediating aggression plasticity for the former two but not the latter brain region. We further hypothesize that the BNST and the LSv may be involved more generally in mediating natural changes in aggression, such as increases often observed after individuals win aggressive interactions against conspecifics.
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Comparative Study
Delayed onset of Huntington's disease in mice in an enriched environment correlates with delayed loss of cannabinoid CB1 receptors.
Huntington's disease (HD) is a late onset progressive genetic disorder characterised by motor dysfunction, personality changes, dementia and premature death. The disease is caused by an unstable expanded trinucleotide (CAG) repeat encoding a polyglutamine stretch in the IT15 gene for huntingtin, a protein of unknown function. Transgenic mice expressing exon one of the human HD gene with an expanded polyglutamine region develop many features of human HD. ⋯ In the brains of humans diagnosed with HD cannabinoid CB1 receptors are selectively lost from the basal ganglia output nuclei prior to the development of other identifiable neuropathology [Neuroscience 97 (2000) 505]. Our results therefore show that an enhanced environment slows the rate of loss of one of the first identifiable neurochemical deficits of HD. This suggests that delaying the loss of CB1 receptors, either by environmental stimulation or pharmacologically, may be beneficial in delaying disease progression in HD patients.
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Neuronal calcium sensor-1 (NCS-1) is a member of the EF-hand calcium-binding protein superfamily which has been implicated in the modulation of a number of neuronal functions. In this study we have examined the expression of NCS-1 in adult rat dorsal root ganglion (DRG) neurons. NCS-1 immunoreactivity was present in most DRG neurons, including many calcitonin gene-related peptide (CGRP) expressing ones. ⋯ NCS-1 immunoreactivity was also present in the dorsal horn of the spinal cord, and in peripheral cutaneous terminals innervating blood vessels, where it was coexpressed with CGRP. In addition, NCS-1 in peripheral nerves was concentrated at nodes and adjoining paranodes. These results suggest novel roles for NCS-1, particularly in relation to channel function at nodes and to the peripheral release of vasoactive peptides.
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Comparative Study
Transgenic mice expressing F3/contactin from the transient axonal glycoprotein promoter undergo developmentally regulated deficits of the cerebellar function.
We have shown that transgenic transient axonal glycoprotein (TAG)/F3 mice, in which the mouse axonal glycoprotein F3/contactin was misexpressed from a regulatory region of the gene encoding the transient axonal glycoprotein TAG-1, exhibit a transient disruption of cerebellar granule and Purkinje cell development [Development 130 (2003) 29]. In the present study we explore the neurobehavioural consequences of this mutation. ⋯ The latter parameters, in particular, were affected also in adult mice, despite the apparent recovery of cerebellar morphology, suggesting that subtle changes of neuronal circuitry persist in these animals after development is complete. These behavioural deficits indicate that the finely coordinated expression of immunoglobulin-like cell adhesion molecules such as TAG-1 and F3/contactin is of key relevance to the functional, as well as morphological maturation of the cerebellum.
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Comparative Study
Neuronal expression of the drug efflux transporter P-glycoprotein in the rat hippocampus after limbic seizures.
In the brain, the efflux transporter P-glycoprotein (Pgp) is predominantly located on the luminal membrane of endothelial cells lining brain microvessels and forming the blood-brain barrier. Many lipophilic drugs, including antiepileptic drugs, are potential substrates for Pgp. Overexpression of Pgp in endothelial cells of the blood-brain barrier has been determined in patients with drug resistant forms of epilepsy such as temporal lobe epilepsy and rodent models of temporal lobe epilepsy and suggested to lead to reduced penetration of antiepileptic drugs into the brain. ⋯ No neuronal Pgp staining was seen in control rats. The expression of Pgp in neurons after limbic seizures was substantiated by determining Pgp encoding genes (mdr1a, mdr1b) in neurons by real time quantitative RT-PCR. Increased Pgp expression in hippocampal neurons is likely to affect the action of drugs with intraneuronal targets and, in view of recent evidence from other cell types, could be associated with prevention of apoptosis which is involved in neuronal damage developing after seizures such as produced by pilocarpine.