Frontal marker

These markers are not of use with low pH separations where most analytes migrate faster than the EOF, which is extremely low. If a peak is still required as an internal standard for correction of migration time, any compound with a fast cathodic electrophoretic mobility will suffice as a frontal marker. We have found that a synthetic peptide containing seven lysine residues and a single tryptophan (K3WK4) functions adequately for this purpose at pH 2.5. A frontal marker may also be useful at higher pH (e.g., when the neutral marker comigrates with a species of interest), where cationic species such as normetanephrine can suffice. 

In contrast, following a treatment regimen of 20 mg/kg MDMA, there were no significant differences in the density of [3H]mazindol-labeled norepinephrine (NE) uptake sites (fmol/mg protein) in the frontal cerebral cortex between saline-treated (159 17) and MDMA-treated (152 5) animals. With respect to the dose of MDMA, serotonin levels appeared to be more readily decreased (45 percent reduction at 5 mg/kg), while comparable reductions in 5-HlAA levels and serotonin uptake sites were noted only at 10 or 20 mg/kg MDMA. This apparent discrepancy among the three serotonergic markers measured in the present study may relate to effects of lower doses of MDMA on synthetic enzyme activity (i.e., TPH), whereas the effects of higher doses of MDMA in reducing all three markers may relate in part to effects on TPH activity and in part to destruction of serotonin neurons as evidenced by decreases in serotonin uptake sites. 

Magnetic resonance spectroscopy studies of COS patients revealed decreases in the ratio of N-acetyl aspartate to creatine (a putative marker of neuronal density) in the frontal cortex (Thomas et ah, 1998) and hippocampus (Bertolino et ah, 1998). These results were similar in direction and extent to those seen in adult patients. 

Neuroimaging techniques assessing cerebral blood flow (CBF] and cerebral metabolic rate provide powerful windows onto the effects of ECT. Nobler et al. [1994] assessed cortical CBE using the planar xenon-133 inhalation technique in 54 patients. The patients were studied just before and 50 minutes after the sixth ECT treatment. At this acute time point, unilateral ECT led to postictal reductions of CBF in the stimulated hemisphere, whereas bilateral ECT led to symmetric anterior frontal CBE reductions. Regardless of electrode placement and stimulus intensity, patients who went on to respond to a course of ECT manifested anterior frontal CBE reductions in this acute postictal period, whereas nonresponders failed to show CBF reductions. Such frontal CBF reductions may reflect functional neural inhibition and may index anticonvulsant properties of ECT. A predictive discriminant function analysis revealed that the CBF changes were sufficiently robust to correctly classify both responders (68% accuracy] and nonresponders (85% accuracy]. More powerful measures of CBF and/or cerebral metabolic rate, as can be obtained with positron-emission tomography, may provide even more sensitive markers of optimal ECT administration. 

Immunostaining for BrdU and markers for immature migrating neurons (PSA-NCAM, /3111-tubulin or Doublecortin) in frontal white matter did not reveal chains... 

Previous studies have reported the generation of neurons in frontal cortex and striatum of normal adult monkeys (Gould et al. 2001 Bedard et al. 2002). We therefore searched for evidence of de novo generation of cells with a neuronal immunophenotype in the striatum and frontal cortex of postischemic monkeys. We first performed double-staining for BrdU and the mature neuronal marker... 

Table 10 Average percentages of colabeling of BrdU with various cell markers in parenchyma of frontal cortex and striatum. BrdU+ cells were sampled for colabeling with either Musashil or Nestin as described in the text...

Using 3H-QNB as a marker for all five subtypes of the mAChRs, an early study reported a significant reduction in the level of mAChR-binding in the frontal cortex of subjects with schizophrenia compared with healthy controls (Bennett et al., 1979). This result was not replicated in two later studies, which reported an increased number of mAChRs in frontal cortex in medicated subjects with schizophrenia (Watanabe et al, 1983 Toru et al., 1988). 

The evidence on predictors and markers of clozapine response has been reviewed (224). Higher baseline clinical symptoms and functioning in the previous years and low cerebrospinal homovanillic acid/5-hydroxyindoleace-tic acid concentrations were identified as reliable, and three potential measures were also identified reduced frontal cortex metabolic activity, reduced caudate volume, and improvement in P50 sensory gating. The authors pointed out that none of these is specific to clozapine, but that this does not reduce their value, instead showing that they do not clarify why clozapine is different from other antipsychotic drugs, for example in terms of efficacy in treatment-resistant patients. 

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