Neuroscience
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Comparative Study
Synaptic loss following depletion of noradrenaline and/or serotonin in the rat visual cortex: a quantitative electron microscopic study.
Biogenic amines have a trophic-like role for the formation and the maintenance of synapses in the CNS. We examined the changes in the number of synaptic profiles in the developing and adult rat visual cortex following selective depletion of noradrenaline and/or serotonin. By the drug-induced decreases in levels of noradrenaline or serotonin between 1 and 2 weeks after birth, the number of synaptic profiles was decreased by 29-55% compared with that of control animals. ⋯ The number of axodendritic synapses was the highest between 2 and 7 weeks after birth, and decreased to 50% at 11 weeks after birth. These data demonstrate that synapses in the rat visual cortex are overproduced during the early developmental period. We suggest that both serotonin and noradrenaline are necessary for synapse formation during the early stages of development of the rat visual cortex.
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Development of serotonin (5HT(1B/1D)) agonists for the acute attack of migraine resulted in considerable interest in their action. The superior sagittal sinus (SSS) was isolated in alpha-chloralose (60 mg/kg, i.p. and 20 mg/kg i.v.i. supplementary 2 hourly) anaesthetised cats. The SSS was stimulated electrically (100 V, 250 micros duration, 0.3 Hz) and neurons of the trigeminocervical complex monitored using electrophysiological methods. ⋯ Alniditan inhibited SSS-evoked trigeminal activity (53+/-6%), an effect abolished after 5-HT(1B) and 5-HT(1D) receptor blockade. LY344864 (5-HT(1F) receptor agonist) inhibited SSS-evoked trigeminal activity (28+/-5%), an effect unaltered by either SB224289 or BRL-15572. It can be concluded that there are inhibitory 5-HT(1B), 5-HT(1D) and 5-HT(1F) receptors in the trigeminocervical complex of the cat. 5-HT(1B) receptor-mediated inhibition is the most potent of the three in terms of inhibition of trigeminovascular nociceptive traffic.
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Comparative Study
Late degeneration of nigro-striatal neurons in ATM-/- mice.
The generation of an Atm -/- mouse model of the human ataxia-telangiectasia (AT) opened new avenues toward a better understanding of the molecular and cellular basis of AT. We have recently reported that 5-month-old Atm-/- mice exhibit severe loss of tyrosine hydroxylase-positive, dopaminergic nigro-striatal neurons, down to 26% of age-matched controls. In the present study we analyzed development of the dopaminergic cell loss in the context of the nigro-striatal system. ⋯ In addition, alpha-synuclein immunopositive bodies were observed in the cortex, striatum and substantia nigra of these mice. The present data indicate that Atm-/- mice exhibit a progressive, age-dependent, reduction in dopaminergic cells of the substantia nigra, followed by a reduction in projection neurons of the striatum. Thus, the Atm-/- mouse may model the extrapyramidal motor deficits seen in AT patients.
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Comparative Study
Sec6 is localized to the plasma membrane of mature synaptic terminals and is transported with secretogranin II-containing vesicles.
The sec6/8 (exocyst) complex is implicated in targeting of vesicles for regulated exocytosis in various cell types and is believed to play a role in synaptogenesis and brain development. We show that the subunits sec6 and sec8 are present at significant levels in neurons of adult rat brain, and that immunoreactivity for the two subunits has a differential subcellular distribution. We show that in developing as well as mature neurons sec6 is concentrated at the inside of the presynaptic plasma membrane, while sec8 immunoreactivity shows a diffuse cytoplasmic distribution. ⋯ Neuronal induction of the PC12 cells with nerve growth factor shows that sec8 is not freely soluble, but may probably interact with cytoskeletal elements. The complex may facilitate the targeting of membrane material to presynaptic sites and may possibly shuttle vesicles from the cytoskeletal transport machinery to presynaptic membrane sites. Thus, we suggest that the exocyst complex serves to modulate exocytotic activity, by targeting membrane material to its presynaptic destination.
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The formation of edema after traumatic brain injury (TBI) is in part associated with the disruption of the blood-brain barrier. However, the molecular and cellular mechanisms underlying these phenomena have not been fully understood. One possible factor involved in edema formation is vascular endothelial growth factor (VEGF). ⋯ The maximum number of astrocytes expressing VEGF was observed 4 days after TBI, and then the levels of astroglial VEGF expression declined gradually. Early invasion of brain parenchyma by VEGF-secreting neutrophils together with a delayed increase in astrocytic synthesis of this growth factor correlate with the biphasic opening of the blood-brain barrier and formation of edema previously observed after TBI. Therefore, these findings suggest that VEGF plays an important role in promoting the formation of post-traumatic brain edema.