Neuroscience
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During development norepinephrine plays a role in determining the morphologic organization of the CNS and the density and future responsiveness of adrenergic receptors. alpha-2 Adrenergic receptors, one of three adrenergic receptor types, regulate important adult CNS functions and may have a distinct role during development. We examined alpha-2 receptor distribution and density in the rat brain at postnatal days 1, 5, 10, 15, 21, 28 and in adults using the antagonist [(3)H]RX821002 for autoradiography. Binding kinetics and pharmacology for alpha-2 adrenergic receptors were the same in adults and neonates. ⋯ Third, some regions demonstrated decreasing or transient expression of alpha-2 adrenergic receptors in the course of postnatal development, including white matter regions, cerebellum and many brainstem nuclei, suggesting specific roles for alpha-2 receptors during development. This study investigates the development of alpha-2 adrenergic receptors in the rat CNS. It demonstrates there is region-specific regulation of alpha-2 receptor development and identifies brain regions where these receptors may play a specific and critical role in the regulation normal development.
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Comparative Study
Voluntary exercise following traumatic brain injury: brain-derived neurotrophic factor upregulation and recovery of function.
Voluntary exercise leads to an upregulation of brain-derived neurotrophic factor (BDNF) and associated proteins involved in synaptic function. Activity-induced enhancement of neuroplasticity may be considered for the treatment of traumatic brain injury (TBI). Given that during the first postinjury week the brain is undergoing dynamic restorative processes and energetic changes that may influence the outcome of exercise, we evaluated the effects of acute and delayed exercise following experimental TBI. ⋯ In contrast, cognitive performance in the acute FPI-RW rats was significantly impaired compared with all the other groups. These results suggest that voluntary exercise can endogenously upregulate BDNF and enhance recovery when it is delayed after TBI. However, when exercise is administered to soon after TBI, the molecular response to exercise is disrupted and recovery may be delayed.
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Psychostimulants and antipsychotic drugs increase mRNA expression of the neuropeptide neurotensin (NT) in the striatum and nucleus accumbens. In the present study, we used mice lacking the dopamine transporter (DAT) to investigate the consequences of a chronic hyperdopaminergic state on NT gene expression. NT mRNA expression was examined under basal conditions and after administration of haloperidol or amphetamine using in situ hybridization with a digoxigenin-labeled NT cRNA probe. ⋯ Amphetamine (10 mg/kg) increased the number of hybridized neurons in the nucleus accumbens shell and fundus striati of wild-type and DAT-/- mice, indicating that the drug acted through a target other than DAT, such as the serotonin or the norepinephrine transporters. The up-regulation of NT mRNA observed in DAT-/- mice may represent an adaptive mechanism in response to constitutive hyperdopaminergia. These results illustrate the profound alterations in the NT system induced by chronic stimulation of DA receptors and underscore the potential clinical relevance of NT/DA interactions in schizophrenia and drug abuse.
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Comparative Study
Differential co-localisation of the P2X7 receptor subunit with vesicular glutamate transporters VGLUT1 and VGLUT2 in rat CNS.
Presynaptic P2X(7) receptors are thought to play a role in the modulation of transmitter release and have been localised to terminals with the location and morphology typical of excitatory boutons. To test the hypothesis that this receptor is preferentially associated with excitatory terminals we combined immunohistochemistry for the P2X(7) receptor subunit (P2X(7)R) with that for two vesicular glutamate transporters (VGLUT1 and VGLUT2) in the rat CNS. This confirmed that P2X(7)R immunoreactivity (IR) is present in glutamatergic terminals; however, whether it was co-localised with VGLUT1-IR or VGLUT2-IR depended on the CNS region examined. ⋯ In other forebrain areas, P2X(7)R-IR co-localised with VGLUT1-IR throughout the amygdala, caudate putamen, striatum, reticular thalamic nucleus and cortex and with VGLUT2-IR in the dorsal lateral geniculate nucleus, amygdala and hypothalamus. Dual labelling studies performed using markers for cholinergic, monoaminergic, GABAergic and glycinergic terminals indicated that in certain brainstem and spinal cord nuclei the P2X(7)R is also expressed by subpopulations of cholinergic and GABAergic/glycinergic terminals. These data support our previous hypothesis that the P2X(7)R may play a role in modulating glutamate release in functionally different systems throughout the CNS but further suggest a role in modulating release of inhibitory transmitters in some regions.
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Comparative Study
A possible role of tryptase in angiogenesis in the brain of mdx mouse, a model of Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is characterized by muscle degeneration and affects the CNS. Dystrophin is absent in muscle and CNS of both DMD patients and mdx mouse, a model of DMD. ⋯ Tryptase, contained in the MC granules, stimulates angiogenesis in vitro and in vivo. We demonstrated for the first time a correlation between the extent of angiogenesis and the number of tryptase-positive neurons and microvessels and suggest that the tryptase contained in the neurons and in the endothelial cells of the mdx mouse brain may be involved in the regulation of angiogenesis taking place in mdx mouse.