Neuroscience
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Intraperitoneal injection of kainic acid in the rat represents a widely used animal model of human temporal lobe epilepsy. Injection of kainic acid induces acute limbic seizures which are accompanied by seizure-induced brain damage and late spontaneous recurrent seizures. There is considerable evidence for an altered transmission of GABA in human temporal lobe epilepsy and in the kainic acid model. ⋯ Some alpha4-, gamma3- and delta-immunoreactivity was also found in astrocytes 48 h after kainic acid injection. Our data indicate an impairment of GABA-mediated neurotransmission due to a lasting loss of GABA(A) receptor containing cells after kainic acid-induced seizures. The seizure-induced loss in GABA(A) receptors within the hippocampus may in part be compensated by increased expression of GABA(A) receptor subunits within the molecular layer of the dentate gyrus and in pyramidal cells.
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Kainic acid-induced seizures in rats represent an established animal model for human temporal lobe epilepsy. The neuropathological sequelae include acute status epilepticus followed by neurodegeneration in the CA1 and CA3 sector of the Ammon's horn and of interneurons in the hilus of the dentate gyrus. After about three weeks spontaneous recurrent seizures become manifest. ⋯ Our data suggest a fast but transient change in the expression of messenger RNAs encoding for different subunits of the GABA(A) receptor in the granule cell layer of the dentate gyrus. This is followed by a lasting augmentation of messenger RNAs encoding different GABA(A) receptor subunits in the same cell layer indicating long-lasting GABAergic inhibition. Changes within the pyramidal cell layer are mostly determined by concomitant neurodegenerative processes.
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Anatomically coupled neurons (17 of 137) and non-coupled neurons (120 of 137), in and near the nucleus tractus solitarius and dorsal motor nucleus (i.e. solitary complex), were studied by rapid perforated patch recording in slices (rat, 150-350 microm thick, postnatal day 0-21) before, during and after exposure to hypercapnic acidosis. Anatomical coupling refers to the intercellular transfer of Lucifer Yellow and Biocytin into adjoining neurons, presumably via gap junctions [see Dean et al. (1997) Neuroscience 80, 21-40]. Eighty-six per cent of the anatomically coupled neurons (12 of 14) were depolarized by hypercapnic acidosis, a response referred to as CO2 excitation or CO2 chemosensitivity. ⋯ It was not determined whether anatomical coupling was affected by hypercapnic acidosis since dye mixture was always administered under normocapnic conditions. The high correlation between anatomical coupling, electrotonic coupling activity and CO2-induced depolarization suggests that cell-cell coupling is an important electroanatomical feature in CO2-excited neurons of the solitary complex. CO2-excited neurons have been hypothesized to function in central chemoreception for the cardiorespiratory control systems, suggesting that cell cell coupling may contribute in part to central chemoreception of CO2 and H+.
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Glial cell line-derived neurotrophic factor was initially identified as a survival factor for developing midbrain dopamine neurons (for reviews, see Refs 17 and 19). Subsequent studies have demonstrated a more wide-spread role for glial cell line-derived neurotrophic factor in the developing and adult CNS. In the adult rat brain, for instance, prior administration of glial cell line-derived neurotrophic factor protects nigrostriatal dopamine neurons from 6-hydroxydopamine-induced damage. ⋯ Following extensive unilateral 6-hydroxydopamine lesions of the medial forebrain bundle, ret immunoreactivity in the substantia nigra and striatum was reduced significantly, to a similar extent as tyrosine hydroxylase immunoreactivity. In contrast, excitotoxic lesions of the striatum, achieved by intrastriatal quinolinic acid injections, resulted in increased ret staining in this brain region. In addition, marked decrements in septal ret immunoreactivity were consequent to complete transections of the fimbria-fornix.
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The importance of receptors for N-methyl-D-aspartate in synaptic plasticity and in triggering long-term pronociceptive changes is explained by their voltage-dependence. This suggests that their contribution to acute nociceptive responses would be determined both by the magnitude of synaptic input and by the level of background excitation. We have now examined the role of N-methyl-D-aspartate receptors in acute nociceptive transmission in the spinal cord. ⋯ The results indicate that under these conditions in vivo, N-methyl-D-aspartate receptors mediate ongoing low-frequency background activity rather than phasic high-frequency nociceptive responses. The effects of N-methyl-D-aspartate antagonists and positive modulators on nociceptive responses are evidently indirect, being secondary to changes in background synaptic excitation. These results cannot be explained simply in relation to the voltage-dependence of N-methyl-D-aspartate receptor-mediated activity; other factors, such as modulation by neuropeptides, must be involved.