Neuroscience
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Comparative Study
Neuroprotective activity of antazoline against neuronal damage induced by limbic status epilepticus.
Imidazoline drugs exert neuroprotective effects in cerebral ischaemia models. They also have effects against mouse cerebellar and striatal neuronal death induced by N-methyl-D-aspartate (NMDA) through the blockade of NMDA currents. Here, we investigated the effects of antazoline on NMDA toxicity and current in rat hippocampal neuronal cultures, and on an in vivo model of status epilepticus. ⋯ On the contralateral side to the pilocarpine injection, only the hippocampal CA3 area was significantly protected in the low-dose group, but all investigated structures were in the high-dose group. In conclusion, antazoline is a potent neuroprotective drug in different models of neuronal primary culture, as previously shown in striatal and cerebellar granule neurons [Neuropharmacology 39 (2000) 2244], and here in hippocampal neurons. Antazoline is also neuroprotective in vivo in the intra-pyriform pilocarpine-induced status epilepticus model.
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Comparative Study
Quantification and localization of kainic acid-induced neurotoxicity employing a new biomarker of cell death: cleaved microtubule-associated protein-tau (C-tau).
Previous studies of neuronal degeneration induced by the neurotoxin, kainic acid, employed silver stain techniques that are non-quantitative or ELISA measurement of the non-neuronal protein, glial fibrillary acidic protein. As previous studies employed biomarkers that were either non-quantitative or non-neuronal, the present study employed a new neuronally localized biomaker of neuronal damage, cleaved microtubule-associated protein (MAP)-tau (C-tau). The time course of kainate neurotoxicity was quantitatively determined in several brain regions in the present study employing a C-tau specific ELISA. ⋯ Similar cleavage of rat MAP-tau to C-tau has been reported after neuronal degeneration induced by neurotoxic doses of methamphetamine and neuronal degeneration resulting from bacterial meningitis. In humans, C-tau proteolysis has been demonstrated to be a reliable biomarker of neuronal damage in traumatic brain injury and stroke where cerebrospinal C-tau levels are correlated with patient clinical outcome. These data suggest that C-tau proteolysis may prove a reliable species independent biomarker of neuronal degeneration regardless of source of injury.
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Electrophysiological recordings were used to investigate the effects of ATP analogues on theta-burst-induced long-term potentiation (LTP) in rat hippocampal slices. alpha,beta-Methylene ATP (alpha,beta-MeATP; 20 microM) decreased LTP from 36+/-9% to 17+/-5%, an effect prevented by adenosine A(1) receptor blockade in accordance with the localised catabolism of ATP analogues into adenosine, leading to adenosine A(1) receptor activation. Thus, to probe the role of extracellular ATP, all experiments were performed with the A(1) receptor selective antagonist, 1,3-dipropyl-8-cyclopentylxanthine (50 nM). In these conditions, alpha,beta-MeATP or 5'-adenylylimido-diphosphate (beta,gamma-ImATP; 20 microM) facilitated LTP by 120%, an effect prevented by the P2 receptor antagonists, pyridoxalphosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS; 20 microM) or suramin (75 microM), as well as by the P2X(1/3)-selective antagonist 8-(benzamido)naphthalene-1,3,5-trisulfonate (10 microM). ⋯ Furthermore, beta,gamma-ImATP (20 microM) enhanced [(3)H]adenosine outflow from rat hippocampal slices by nearly 150%, an effect prevented by PPADS (20 microM) or suramin (75 microM). The adenosine transport inhibitors, nitrobenzylthioinosine (5 microM) and dipyridamole (10 microM) also prevented beta,gamma-ImATP (20 microM)-induced [(3)H]adenosine outflow and facilitation of LTP. These results suggest that ATP analogues facilitate LTP through P2 receptor activation that mainly triggers adenosine release leading to the activation of adenosine A(2A) receptors.
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Somatosensory stimulation of primary somatosensory cortex (SI) using frequency discrimination offers a direct, well-defined and accessible way of studying cortical decisions at the locus of early input processing. Animal studies have identified and classified the neuronal responses in SI but they have not yet resolved whether during prolonged stimulation the collective SI response just passively reflects the input or actively participates in the comparison and decision processes. This question was investigated using tomographic analysis of single trial magnetoencephalographic data. ⋯ When only correct responses from the above two groups were used, the difference was even higher at later latencies (approximately 650 ms). For one subject who had enough trials of same perception to different input frequencies, e.g. responded 21 Hz to Stim2 at 21 Hz (correct) and 26-29 Hz (error), we found the sustained difference only before 650 ms. Our results suggest that SI is involved with the analysis of an input frequency and related to perception and decision at different latencies.
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Converging evidence in schizophrenia suggests prefrontal cortical neuronal deficits that correlate with exaggerated subcortical dopamine (DA) functions: Excitotoxic lesion of the ventral hippocampus (VH) in neonatal rats is widely considered a putative animal model of schizophrenia as they lead to characteristic post-pubertal emergence of behavioral and cognitive abnormalities suggesting a developmental change in the neural circuits comprising the prefrontal cortex (PFC) and subcortical DA. Nerve growth factor inducible-B (NGFI-B, also known as Nur77), an orphan nuclear receptor and transcriptional regulator, is constitutively expressed in the target structures of DA pathways. It acts as an immediate early gene with rapid modulation of its mRNA expression by stress, DA and antipsychotic drugs. ⋯ Amphetamine treatment increased the expression of NGFI-B mRNA in the mPFC, CC, striatum and NAcc in both control and lesioned animals of both ages. Interestingly, however, striatal and NAcc regions of lesioned rats showed a significantly greater effect of amphetamine at PD56. The data suggest that nVH lesions lead to delayed changes in PFC gene expression along with functional DAergic hyperactivity in subcortical regions.