Cross-correlation analysis of septohippocampal neurons during theta-rhythm

The activity from 55 septohippocampal neuron pairs was examined in rats anesthetized with urethane. In addition to the statistical characterization of the firing patterns of the recorded units, the functional interactions between pairs of neurons and between neurons and hippocampal theta (theta) waves were investigated with cross-correlation techniques. Pairs were classified according to the rhythmic or non-rhythmic discharge pattern of their neurons. (a) theta-Pairs were those in which both the medial septal (MS) and hippocampal (HPC) units were rhythmic (type 1 units). (b) Pairs with a rhythmic and a theta-related non-rhythmic unit (type 2 unit) were called mixed pairs. (c) Pairs composed of type 2 units were called type 2 pairs. theta-Pairs showed periodic cross-correlations and frequently fired with a phase difference which could change in different pairs. Mixed pairs also showed periodic cross-correlations although one of the units was non-rhythmic. Type 2 pairs showed non-periodic positive cross-correlations. Our data provide new information regarding the temporal relationship between MS and HPC rhythmic activities supporting the role of the MS in providing the afferent timing for the generation of theta-rhythm in the HPC.     

Age, personality, and the Holtzman Inkblot Technique

Recent longitudinal studies using personality questionnaires and ratings have shown remarkable stability across the adult years. In an investigation of age changes and differences in personality as measured by the Holtzman Inkblot Technique (HIT), ninety-three men and women aged twenty-five to ninety were administered Form A of the HIT; forty-four of these were retested one to three years later. Stability coefficients ranged from .07 for Form Appropriateness to .73 for Form Definiteness, with most variables showing significant but moderate stability. Repeated measures analyses of variance showed increases in six variables and decreases in two others, but only one of these changes was paralleled by cross-sectional age differences. Correlations with self-report measures of the broad personality domains of neuroticism, extraversion, and openness to experience failed to show hypothesized relations, and the associations seen were attributable to chance. It was concluded that the HIT measures perceptual-cognitive variables that are moderately stable in adulthood.     

Evidence that peroxynitrite affects human osteoblast proliferation and differentiation.

Peroxynitrite (PN), a nitric oxide (NO*)-derived anion, has been associated with NO* damage in various cell types. We examined the effects of adding PN to cultured human osteoblast-like (hOB) cells obtained after hip arthroplasty. Exposure to PN (0.1-0.4 mM) decreased both hOB proliferation and differentiation, measured by [3H]thymidine uptake and alkaline phosphatase production, respectively. Incubation with 3-morpholinosydnonimine (SIN-1; 0.25-1 mM), an NO* and O2- donor that leads to PN release, also reduced both hOB proliferation and differentiation. Coincubation with both superoxide dismutase (SOD; 100 U/ml) and catalase (CAT; 50 U/ml), rendering SIN-1 a pure NO* donor, reversed its effects on hOB proliferation and differentiation. However, SIN-1-induced NO* production, measured by nitrite release to the hOB medium, was not altered by cotreatment with SOD and CAT. Expression of nitrotyrosine by hOB, a marker of PN action, was significantly increased after SIN-1 addition, as compared with untreated cells, as revealed by Western blot analysis. Interleukin-1alpha (IL-1alpha) and interferon gamma (IFN-gamma) but not tumor necrosis factor alpha (TNF-alpha) also significantly increased nitrotyrosine expression in these cells. These data show that PN is at least partially responsible for osteoblast derangement by NO* and that cytokines released during inflammatory arthropathies can induce PN production in hOB cells.     

Interaction of short chain aliphatic alcohols with muscarinic receptor-stimulated phosphoinositide metabolism in cerebral cortex from neonatal and adult rats.

Muscarinic receptor-stimulated phosphoinositide metabolism has been recently suggested as a possible target for the neurotoxic effects of ethanol during brain development. Since two other alcohols, tertiary butanol and n-propanol, have been shown to cause microencephaly in the rat when administered during the brain growth spurt, in the present study we investigated the in vitro effects of five short chain aliphatic alcohols on muscarinic receptor-stimulated phosphoinositide metabolism in cerebral cortical slices from 7 day-old rats. In neonatal animals all alcohols tested inhibited carbachol (1 mM)-stimulated [3H]inositol phosphates accumulation in a dose- and time-dependent manner. The order of potency was t-butanol greater than n-propanol greater than or equal to iso-propanol greater than ethanol greater than methanol. After 90 min of incubation, ethanol, n-propanol and t-butanol caused a significant inhibition of muscarinic receptor-stimulated inositol metabolism at doses as low as 15 - 50 mM, comparable to the blood concentrations reached after in vivo administration of doses able to induce developmental neurotoxicity. The inhibitory effect of ethanol was additive to that of iso-propanol or t-butanol. Differently from these effects in 7 day-old rats, in cortical slices from adult animals methanol and ethanol had no effect on carbachol-stimulated phosphoinositide metabolism, while the two propanol isomers and t-butanol were less effective than in neonatal animals. These results suggest that muscarinic receptor-coupled phosphoinositide metabolism might be a common neurochemical target for the developmental neurotoxicity of short chain aliphatic alcohols.     

Delayed increase of Ca2+ influx elicited by glutamate: role in neuronal death

The mechanism of delayed neurotoxicity, triggered by glutamate, was studied in 7-8-day-old primary cultures of rat cerebellar granule cells. Treatment of cultures for 15 min with 50 microM glutamate in Mg2+ -free medium, followed by removal of the excitoxin, resulted in neuronal death, which started to appear 2-3 hr after the termination of glutamate treatment. The number of dead neurons increased gradually in the next few hours and 80-85% of neurons were found dead 24 hr later. Antagonists of N-methyl-D-aspartate-sensitive glutamate receptors (phencyclidine) or 1.2 mM MgCl2, but not the antagonist of N-methyl-D-asparatate-insensitive glutamate receptors (6-cyano-7-nitroquinoxaline-2,3-dione), abolished the neurotoxic effect of kainate. Development of glutamate-induced neuronal death depends strongly on Ca2+. Removal of extracellular Ca2+ (with 1mM ethyleneglycol-bis-(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid) immediately after the termination of glutamate exposure and before the appearance of the early signs of neuronal death (post-glutamate period) dramatically reduced neuronal degeneration. Neurotoxic concentrations of glutamate induced sustained increase of 45Ca2+ uptake in the post-glutamate period. The delayed increase of 45Ca2+ uptake, as well as the delayed neurotoxicity, were not affected by post-glutamate treatment with phencyclidine, dibenzocyclohepteneimine; DL-2-amino-5-phosphonovalerate, or MgCl2 or with voltage-dependent Ca2+ channel blockers (nitrendipine, verapamil, diltiazem). Neurotoxic concentrations of glutamate also induced a delayed sustained increase of [3H]phorbol-12,13-dibutyrate binding, reflecting an increased translocation of protein kinase C (PKC) from cytosol to the cell membrane during the post-glutamate period. Pretreatment of neurons with the ganglioside GT1b (trisialosylgangliotetraglycosylceramide), followed by removal of free GT1b from the incubation medium, prevented PKC translocation, the sustained increase of 45Ca2+ uptake in the post-glutamate period, and the delayed neuronal death. We suggest that the sustained activation and translocation of PKC primed by glutamate receptor stimulation may be the triggering event causing the protracted increase of neuronal Ca2+ influx. This influx is insensitive to voltage-dependent Ca2+ channel blockers and glutamate receptor antagonists. It appears that this delayed increase of Ca2+ influx may be important in causing neuronal death.     

Efficacy of adjunctive carbamazepine in the treatment of chronic schizophrenia

Six treatment-resistant schizophrenic patients were given a ten-week single-blind trial of carbamazepine. Treatment resistance was determined on the basis of documented failure to respond to treatment with at least three neuroleptic drugs from two different chemical classes. The adjunctive use of carbamazepine resulted in a significant improvement of the negative symptoms of schizophrenia. These symptoms are often poorly responsive to conventional antipsychotic drugs. Therefore, controlled studies should be performed to further assess the possible efficacy of carbamazepine in schizophrenia.