The status of oral hygiene in cleft lip, palate patients after surgical correction.

UNLABELLED: The cleft lip and palate patients usually present a number of problems viz. altered oral anatomy leading to changes in oral physiology diminishing the self-cleansing ability of individual. The handicapped children are unable to maintain their oral hygiene properly. The present study was formulated with the aim that does normalization of oral anatomy have its effect on improvement of oral hygiene? An assessment of oral hygiene index-simplified was performed between preoperative and postoperative values in the same patient at KGMU and KGDU. A total of 50 cases were recorded in two groups of 25 each: (i) 6 years. The observations are statistically analyzed by paired 't' test to get the significance of results. RESULTS: The data analyzed showed the significant decrease in oral hygiene indices observed in both groups. A relative significance in oral hygiene status following surgery was observed. Both groups expressed greater significance when compared pre and postoperatively which is indicative of considerable improvement of oral hygiene after surgical correction. The study concludes that oral hygiene improves more in older cleft lip-palate cases following reconstruction of palatal vault, premaxilla and anterior lip seal by secondary bone grafting method when compared with oral hygiene indices results in primary periosteoplasty cases. The surgical correction of cleft lip palate enhances self-cleaning ability and better compliance to maintain oral hygiene in children as the age advances.

Radicular dens invaginatus--a case report.

Case report showing classical Radicular dens invaginatus; along with in vitro illustrations of the extracted tooth and RVG (Radiovisiography) after radiopaque dye injection.

Archform in cleft palate--a computerized tomographic classification.

This prospective study was conducted in King George's Medical College, Lucknow, India amongst fifty cleft lip and palate cases to study the various arch forms. The maxillary arch form was traced from Computer Tomograph sections of all the cases pre and post-operatively. The various patterns of arch forms as observed from CT tracings exhibiting U & V shaped with sub-types denominated as posteriorly--convergent (c), divergent (d) and parallel (p). This simplified classification can be used in pediatric dentistry practice.

Effects of voluntary ethanol intake on the expression of Ca(2+) /calmodulin-dependent protein kinase IV and on CREB expression and phosphorylation in the rat nucleus accumbens.

To define the molecular basis of alcohol drinking behaviors, the effects of voluntary ethanol intake on the expression of Ca(2+)/calmodulin-dependent protein kinase IV (CaM kinase IV) and on the expression and phosphorylation of cAMP responsive element binding protein (CREB) [corrected] in the nucleus accumbens (NAc), central amygdala, and frontal cortex of rats were investigated. Voluntary ethanol intake significantly decreased the expression of CaM kinase IV and CREB phosphorylation but not of CREB protein levels [corrected], specifically in the shell of NAc. These changes were not observed in the core of NAc, central amygdala and frontal cortex. Mianserin treatment significantly attenuated ethanol intake and antagonized the voluntary ethanol-induced reduction in expression of CaM kinase IV and CREB phosphorylation in the shell of NAc. This is the first evidence to suggest that decreased CaM kinase IV-dependent CREB phosphorylation in the shell region of NAc may play a role in the reward mechanisms of alcohol drinking.

Hyperactive phosphoinositide signaling pathway in platelets of depressed patients: effect of desipramine treatment.

There is some evidence to suggest that certain neurotransmitter receptors, such as adrenergic and serotonergic receptors and receptor-linked signaling systems, may be altered in depression. Serotonin(2A) and alpha(2)-adrenergic receptors are linked to the phosphoinositide (PI) signaling system in platelets and brain. To examine if the PI signaling system is altered in depression, we studied thrombin- and sodium fluoride-stimulated inositol phosphate(1) (IP(1)) formation before and during desipramine (DMI) treatment in platelets of depressed patients and normal control subjects. We determined thrombin- and sodium fluoride-stimulated IP(1) formation in platelets obtained from hospitalized depressed patients during a drug-free baseline period and after 6 weeks of DMI treatment, and drug-free non-hospitalized normal control subjects. Depressed subjects were diagnosed according to DSM-IV criteria, and severity of illness was assessed with the Hamilton Depression Rating Scale. We observed that thrombin-stimulated IP(1) formation in platelets of depressed patients was significantly higher compared with that of normal control subjects. There were no significant differences in sodium fluoride-stimulated IP(1) formation between depressed patients and normal control subjects. We also did not find any significant effect of treatment with DMI on either thrombin- or sodium fluoride-stimulated IP(1) formation in platelets of depressed patients, which continued to be significantly higher after 6 weeks of treatment with DMI, compared with normal control values. Our studies found a hyperactive PI signaling system in platelets of depressed patients. This hyperactive system may be related either to an increased number of thrombin receptors or to a generalized overstimulation of this pathway; however, since we did not observe any differences in sodium fluoride-stimulated IP(1) formation, it appears that, although the sites distal to the receptors may be altered, this abnormality is probably not related to the abnormalities in G proteins.

Estrogen modulation of the cyclic AMP response element-binding protein pathway. Effects of long-term and acute treatments.

Actions of estrogen include mechanisms leading to alterations in gene transcription that may be independent of nuclear estrogen receptors, as well as those involving direct action of the estrogen receptor on the genome. Also, the influence of estrogen in the brain appears to extend well beyond areas associated with reproduction and may include forebrain areas linked to affective and cognitive behaviors. We investigated the effects of acute and long-term estradiol benzoate (E2) treatment on total and phosphorylated cyclic AMP responsive element-binding (CREB) protein levels and on cyclic AMP response element (CRE)-DNA binding in forebrain areas of ovariectomized (OVX) rats. Long-term E2 treatment increased CRE-DNA binding in the amygdala but not in hippocampus, frontal cortex, or cerebellum. The increase in CRE-DNA binding in the amygdala was associated with increased levels of total and phosphorylated CREB (pCREB) protein during protracted E2 exposure. To localize the estrogenic effect in the amygdala and determine if an effect in one hippocampal region was masked by a lack of effect in another subregion, we performed immunolabeling of pCREB in brain structures of chronically treated OVX animals with or without E2. This treatment resulted in a significant increase in relative total immunolabeled nuclei in the anteroventral subdivision of the medial amygdala. In the hippocampus, a significant increase in relative total immunolabeled nuclei was seen in the CA1 and CA3 regions, but not in the dentate gyrus or hilus of the dentate gyrus. Acute E2 treatment resulted in increased CRE-DNA binding in the frontal cortex but not in amygdala, hippocampus, or cerebellum. However, no changes in levels of total CREB or pCREB protein were observed in the frontal cortex under E2 treatment. No changes were observed either in basal or cAMP-stimulated protein kinase A (PKA) activity or in PKA-alpha catalytic subunit immunoreactivity in the amygdala or the frontal cortex. Our study indicates that both long-term and acute treatments with estrogens influence the function of CREB in specific brain structures.

Estrogen affects the expression of Ca2+/calmodulin-dependent protein kinase IV in amygdala.

We examined the effects of long-term estradiol benzoate (E2) treatment on protein expression of Ca2+/calmodulin-dependent protein kinase IV (CaMK IV) in the amygdala of ovariectomized (OVX) rats. Western blot analysis revealed increased protein levels of CaMK IV in the nuclear but not in the membranal or cystolic fraction of total amygdala in E2-treated compared to OVX rats. Significant increases in levels of CaM kinase IV gold immunolabeling were seen in the medial and basomedial, but not in the central or basolateral, amygdala of E2 compared to OVX rats, indicating the neuroanatomical heterogeneity of the E2 effect. These results suggest that CaMK IV may act as a molecular target for actions of estrogen in the amygdala of rats.

cAmp signaling cascade: a promising role in ethanol tolerance and dependence.

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Subhash C. Pandey and Toshikazu Saito. The presentations were (1) Action of ethanol on cAMP signaling pathways, by M. Yoshimura; (2) Alterations in the G protein adenylyl cyclase system and their mRNA levels in alcoholics, by H. Sohma; (3) The role of the CREB gene transcription factor in ethanol dependence and preference, by Subhash C. Pandey; and (4) The efficacy of adenylyl cyclase signal transduction to the nucleus in primary alcoholics, by M. E. Götz.

Effects of protracted nicotine exposure and withdrawal on the expression and phosphorylation of the CREB gene transcription factor in rat brain.

Addiction to nicotine may result in molecular adaptations in the neurocircuitry of specific brain structures via changes in the cyclic AMP-responsive element binding protein (CREB)-dependent gene transcription program. We therefore investigated the effects of chronic nicotine exposure and its withdrawal on CREB and phosphorylated CREB (p-CREB) protein levels in the rat brain. We report here that chronic nicotine exposure (1-h withdrawal) had no effect on the expression of CREB and p-CREB in the rat cortex and amygdala. On the other hand, decreases in the expression of CREB protein and phosphorylation of CREB occur in the cingulate gyrus, and in the parietal and the piriform but not in the frontal cortex during nicotine withdrawal (18 h) after nicotine exposure. It was also observed that CREB and p-CREB protein levels were significantly decreased in the medial and basolateral, but not in the central amygdala during nicotine withdrawal (18 h) after chronic nicotine exposure. Furthermore, it was found that nicotine withdrawal (18 h) after chronic nicotine exposure leads to decreased CRE-DNA binding without modulating cAMP-dependent protein kinase A activity in the cortex and the amygdala of rats. In addition, chronic nicotine treatment produced anxiolytic effects whereas nicotine withdrawal (18 h) produced anxiety in rats as measured by the elevated plus-maze test. These results provide the first evidence that decreased CREB activity and/or expression in specific cortical and amygdaloid brain structures may be involved in the underlying molecular mechanisms of nicotine dependence.

Effects of chronic ethanol intake and its withdrawal on the expression and phosphorylation of the creb gene transcription factor in rat cortex.

This investigation examined the effects of chronic ethanol treatment (15 days) and its withdrawal (24 h) on the expression and phosphorylation of cyclic AMP-response element-binding (CREB) protein in the rat cortex. The effects of chronic ethanol treatment and withdrawal on protein kinase A (PKA) activity and on the expression of the regulatory RII-beta- and the alpha-subtype catalytic subunits of PKA, and on the protein expression of Ca(2+)/calmodulin-dependent protein kinase IV (CaM kinase IV) and calcineurin in the rat cortex were also investigated. It was found that ethanol withdrawal but not ethanol treatment produced a significant decrease in the phosphorylated CREB (p-CREB) and CaM kinase IV protein levels in the frontal, parietal, and piriform cortex. Ethanol treatment and its withdrawal had no effect on the protein levels of total CREB in the frontal, parietal, and piriform cortex. On the other hand, ethanol treatment produced a significant reduction in the protein levels of CREB, p-CREB, and CaM kinase IV in the cingulate gyrus, and these changes reverted to normal levels during ethanol withdrawal. Total CREB protein levels were significantly higher in the cingulate gyrus during ethanol withdrawal. It was also observed that mRNA levels of CREB were significantly higher in the rat cortex during ethanol withdrawal but not during ethanol treatment. The protein levels of RII-beta- and alpha-subtype catalytic subunits of PKA and PKA activity were not modified in the rat cortex by chronic ethanol treatment and its withdrawal. Furthermore, the expression of calcineurin in the rat cortex was not altered during ethanol treatment and withdrawal. Taken together, these results suggest the possibility that decreased CREB-dependent events in the neurocircuitry of the frontal, parietal, and piriform cortex may play an important role in the phenomenon of alcohol dependence and also that decreased CREB-dependent events in the neurocircuitry of the cingulate gyrus may play a role in alcohol tolerance.

Blockade of cyclic AMP-responsive element DNA binding in the brain of CREB delta/alpha mutant mice.

The cAMP-responsive element binding protein (CREB) gene transcription factor has been implicated in the synaptic plasticity and memory. Here, we investigated the mechanisms of CREB and/or cyclic AMP-responsive element modulatory protein (CREM) binding to CRE sites in brain tissues. CRE-DNA binding was determined in nuclear extracts obtained from the several brain structures of wild-type and CREB delta/alpha mutant mice. It was found that antibodies to CREB, phosphorylated CREB, and CREM supershifted the CRE-DNA binding complex in cortical nuclear extracts from wild-type mice, which suggests that the CRE-DNA binding complex contains both CREB and CREM proteins. In contrast, CRE-DNA binding is abolished in the cortex, hippocampus, cerebellum, and amygdala of CREB delta/alpha mutant mice. Because the CREB delta and alpha isoforms have been deleted in CREB mutant mice, consequently, other forms of CREB, such as CREB-beta and CREM, are up-regulated. These results suggest that the binding of CREM to CRE sites requires the presence of CREB delta/alpha, and that CREB-beta may be inefficient in binding to CRE-sites. Thus, these results indicate that CREB delta/alpha mutant mice are a useful animal model for studying the functional role of CREB-dependent gene expression.

Cellular localization of serotonin(2A) (5HT(2A)) receptors in the rat brain.

The serotonin(2A) (5HT(2A)) receptors have been shown to play an important role in several psychiatric disorders, including depression, schizophrenia, and alcoholism. This immunohistochemical study examined the cellular localization of 5HT(2A) receptors in various rat brain structures (olfactory, striatum, cortex, hippocampus, and amygdala). The colocalization of 5HT(2A) receptors in astrocytes was performed by double-immunofluorescence staining of 5HT(2A) receptors and of glial fibrillary acidic protein (GFAP) using confocal laser microscopy. 5HT(2A) receptor immunolabeling was observed in olfactory bulbs, neostriatum, hippocampus, amygdala, and neocortex. Somata and dendrites of pyramidal cells in the frontal cortex (layer V) were densely labeled with 5HT(2A) receptors. In several other brain structures (hippocampus, amygdala, striatum, olfactory structures), 5HT(2A) receptor immunolabeling was found in cell bodies and processes of neurons. 5HT(2A) receptor immunolabeling was also observed in GFAP-positive cells of the various brain structures we investigated (layers I/VI of the neocortex, corpus callosum, hippocampal fissure and hilus, and amygdala). These results indicate that 5HT(2A) receptors are expressed in neurons and astrocytes and suggest the possibility that not only neuronal but also glial 5HT(2A) receptors have functional implications in psychiatric disorders.

Neuroadaptational changes in DNA binding of stimulatory protein-1 and nuclear factor-kB gene transcription factors during ethanol dependence.

To define the molecular basis of ethanol dependence, the changes in gene transcription factor stimulatory protein-1 (SP1) and nuclear factor-kB (NF-kB) DNA binding activities were investigated in the rat cortex and hippocampus during ethanol treatment (15 days) and its withdrawal. It was found that both protracted ethanol treatment and its withdrawal (12, 24, or 72 h) had no effect on NF-kB DNA binding activity in the rat cortex and hippocampus. Time-course studies of the changes in SP1 DNA binding activity during ethanol withdrawal (0, 12, 24, and 72 h) after protracted ethanol exposure indicated that SP1 DNA binding in the rat cortex was significantly decreased at 0 h, and that it remained decreased at 12, 24, and 72 h of withdrawal. On the other hand, SP1 DNA binding activity did not change in the rat hippocampus during ethanol treatment but was significantly decreased at 12, 24, and 72 h of withdrawal. These results suggest the possibility that decreased SP1-dependent gene transcription in the rat cortex and hippocampus may be associated with the molecular mechanisms of ethanol dependence.

Low phosphoinositide-specific phospholipase C activity and expression of phospholipase C beta1 protein in the prefrontal cortex of teenage suicide subjects.

OBJECTIVE: The enzyme phosphoinositide-specific phospholipase C (PI-PLC) is a component of the phosphoinositide signal transduction system. Other components of this system have been found to be abnormal in adults and adolescents who have committed suicide, and so the authors examined whether PI-PLC activity and protein expression of PLC isozymes are abnormal in postmortem brains of teenage suicide subjects. METHOD: PI-PLC activity and protein expression of the PLC beta1, delta1, and gamma1 isozymes were examined in Brodmann's areas 8 and 9 of postmortem brains obtained from 18 teenage suicide subjects and 18 matched comparison subjects. PI-PLC activity was determined by enzymatic assay, and protein expression of the PLC isozymes was determined by the Western blot technique. RESULTS: Compared with the normal subjects, the teenage suicide subjects had significantly lower PI-PLC activity and immunolabeling of the specific PLC beta1 isozyme in both membrane and cytosol fractions of Brodmann's areas 8 and 9 combined (prefrontal cortex). There was also a significant correlation between PI-PLC activity and protein levels of the PLC beta1 isozyme in the brains of the teenage suicide subjects. There was no significant difference in PI-PLC activity or level of PLC beta1 protein between the suicide subjects with a history of mental disorders and those with no history of mental disorders; however, both groups had significantly lower PI-PLC activity and expression of PLC beta1 protein than the normal subjects. CONCLUSIONS: Low PI-PLC activity and expressed levels of the PLC beta1 isozyme in postmortem brains of suicide subjects may have clinical relevance in the pathophysiology of suicidal behavior.

Involvement of the cyclic AMP-responsive element binding protein gene transcription factor in genetic preference for alcohol drinking behavior.

BACKGROUND: Cyclic adenosine 3',5'-monophosphate (cAMP)-responsive element binding (CREB) protein is a gene transcription factor that can integrate the signals mediated via the cAMP second messenger cascade at the gene expression level, which then controls neuronal functions. METHODS: To examine if the protein kinase A --> CREB signaling cascade is involved in genetic alcohol drinking preference, different measures of CREB were determined in various brain structures of alcohol-preferring (P) and alcohol-nonpreferring (NP) rats. RESULTS: We show here that CRE-DNA binding activity is significantly decreased in the amygdala but not in the cortex, hippocampus, or striatum of P rats compared with NP rats. The levels of total CREB and phosphorylated CREB protein in the amygdala are significantly lower in P rats compared with NP rats. On the other hand, levels of the alpha-isoform of the catalytic subunit of protein kinase A protein, and basal as well as cAMP-stimulated protein kinase A activity are similar in the amygdala of both P and NP rats. CONCLUSIONS: Because P and NP rats are genetically bred for high and low alcohol drinking behavior, respectively, these results suggest the possibility that decreased expression of CREB protein in the amygdala may be associated with the high alcohol drinking behavior of P rats.

Regulation of AP-1 gene transcription factor binding activity in the rat brain during nicotine dependence.

The effects of acute and chronic nicotine treatment on activator protein-1 (AP-1) gene transcription factor binding activity in the rat cortex were investigated. AP-1 DNA binding activity was determined by the electrophoretic gel mobility shift assay. It was observed that 1 h after acute nicotine treatment (single injection) AP-1 DNA binding activity was significantly increased in the rat cortex. On the other hand, AP-1 DNA binding activity in the rat cortex was not altered at 1 and 8 h of nicotine withdrawal after repeated nicotine treatment (10 days). However, at 18 and 24 h of nicotine withdrawal after 10 days of nicotine treatment, AP-1 DNA binding activity was significantly decreased in the rat cortex. Thus, these findings suggest that desensitization of cortical AP-1 DNA binding activity may be involved in the neuroadaptational mechanisms to nicotine dependence.

Potential role of the gene transcription factor cyclic AMP-responsive element binding protein in ethanol withdrawal-related anxiety.

This investigation examined the effects of acute and chronic ethanol exposure and its withdrawal on the cAMP-responsive element binding protein (CREB) and the activator protein-1 (AP-1) gene transcription factors in the rat brain. The anxiogenic effects of ethanol withdrawal after acute or protracted ethanol treatment of rats were measured by the elevated plus-maze (EPM) test. It was observed that ethanol withdrawal after acute ethanol treatment has no effect on open-arm activity (percent of open-arm entries and the mean percent of time spent on the open arms) of rats on the EPM test. On the other hand, the time course studies of the development of anxiety during ethanol withdrawal (0, 12, 24, and 72 h) after 15 days of ethanol treatment indicate that peak anxiety (significant decrease in open-arm activity) occurred at 24 h of ethanol withdrawal in rats. It was observed that acute ethanol treatment and its withdrawal (24 h) had no effect on CRE- or AP-1 DNA-binding activities in the rat cortex as determined by the electrophoretic gel-mobility shift assay. It was also found that chronic ethanol treatment and its withdrawal (24 h) had no effect on AP-1 DNA-binding activity in the rat cortex. Investigation of the time course studies of changes in CRE-DNA-binding activity during ethanol withdrawal (0, 12, 24, and 72 h) after 15 days of ethanol treatment indicated that the peak reduction of CRE-DNA-binding activity occurred at 24 h of ethanol withdrawal. The changes in the immunolabeling of the CREB-related target, that is, brain-derived neurotrophic factor (BDNF), in the rat cortex during chronic ethanol treatment and its withdrawal (24 h) were examined using western blotting. It was found that 24 h but not 0 h of ethanol withdrawal after 15 days of ethanol treatment caused a significant decrease in the immunolabeling of BDNF in the rat cortex. Fluoxetine (alone) treatment of rats for 1 or 15 days had no effect on open-arm activity and cortical CRE-DNA-binding activity. However, when fluoxetine was administered concurrently with ethanol treatment for 15 days, it caused a reversal of the anxiogenic effects of ethanol withdrawal and antagonized the down-regulation of CRE-DNA-binding activity and of the decrease in immunolabeling of BDNF in the cortices of ethanol-withdrawn rats. On the other hand, acute fluoxetine treatment produced normalization of the reduction of cortical CRE-DNA binding in ethanol-withdrawn rats (24 h) but did not reach the level of significance compared with normal control rats. Acute fluoxetine treatment had no effect on anxiety in ethanol-withdrawn rats. Taken together, these results suggest the possibility that decreased CRE-DNA-binding activity in the rat cortex may be associated with the molecular mechanisms of ethanol dependence (i.e., ethanol withdrawal-related anxiety).

Neuronal signaling systems and ethanol dependence.

In recent years there have been remarkable developments toward the understanding of the molecular and/or cellular changes in the neuronal second-messenger pathways during ethanol dependence. In general, it is believed that the cyclic adenosine 3',5'-monophosphate (cAMP) and the phosphoinositide (PI) signal-transduction pathways may be the intracellular targets that mediate the action of ethanol and ultimately contribute to the molecular events involved in the development of ethanol tolerance and dependence. Several laboratories have demonstrated that acute ethanol exposure increases, whereas protracted ethanol exposure decreases, agonist-stimulated adenylate cyclase activity in a variety of cell systems, including the rodent brain. Recent studies indicate that various postreceptor events of the cAMP signal transduction cascade (i.e., Gs protein, protein kinase A [PKA], and cAMP-responsive element binding protein [CREB]) in the rodent brain are also modulated by chronic ethanol exposure. The PI signal-transduction cascade represents another important second-messenger system that is modulated by both acute and chronic ethanol exposure in a variety of cell systems. It has been shown that protracted ethanol exposure significantly decreases phospholipase C (PLC) activity in the cerebral cortex of mice and rats. The decreased PLC activity during chronic ethanol exposure may be caused by a decrease in the protein levels of the PLC-beta 1 isozyme but not of PLC-delta 1 or PLC-gamma 1 isozymes in the rat cerebral cortex. Protein kinase C (PKC), which is a key step in the PI-signaling cascade, has been shown to be altered in a variety of cell systems by acute or chronic ethanol exposure. It appears from the literature that PKC plays an important role in the modulation of the function of various neurotransmitter receptors (e.g., gamma-aminobutyrate type A [GABAA], N-methyl-D-aspartate [NMDA], serotonin2A [5-HT2A], and 5-HT2C, and muscarinic [m1] receptors) resulting from ethanol exposure. The findings described in this review article indicate that neuronal-signaling proteins represent a molecular locus for the action of ethanol and are possibly involved in the neuro-adaptational mechanisms to protracted ethanol exposure. These findings support the notion that alterations in the cAMP and the PI-signaling cascades during chronic ethanol exposure could be the critical molecular events associated with the development of ethanol dependence.

Benzodiazepine receptors in the post-mortem brain of suicide victims and schizophrenic subjects.

To examine the role of benzodiazepine (BZ) receptors in suicide and schizophrenia, we determined BZ receptors in post-mortem brain (Brodmann's area 10) obtained from suicide victims, schizophrenic patients, and control subjects using [3H]RO15-1788 as the radioligand. The maximum number of binding sites (Bmax) of BZ receptors in the cortex of suicide victims was significantly higher compared with controls, but this increase was mainly due to those suicide victims who died by violent means and whose Bmax was significantly higher than of those who died by non-violent means or control subjects. In schizophrenic patients, Bmax was not significantly different from that of control subjects. When the schizophrenic subjects were separated into two groups, those on neuroleptics and those off neuroleptics for at least 12 months, however, the mean Bmax of BZ receptors in the prefrontal cortex in post-mortem brain obtained from schizophrenic patients on neuroleptics was significantly lower than Bmax in drug-free schizophrenic patients or normal controls. There were no significant differences among groups in values of the apparent dissociation constant (KD) of [3H]RO15-1788 binding. These results suggest that BZ receptors are up-regulated in the cortex of suicide victims, specifically those who used violent means, and that neuroleptic treatment may result in decreased central BZ receptor binding in the cortex of schizophrenic patients. Thus, the method of suicide and previous exposure to neuroleptics should be considered in the interpretation of data on BZ receptors.

Protein kinase C in the postmortem brain of teenage suicide victims.

Increased serotonin2A (5-HT2A) receptors have been reported in the postmortem brain of suicide victims. To examine if this increase is associated with the dysregulation of postreceptor sites in the signaling cascade, we determined [3H]phorbol dibutyrate (PDBU) binding to protein kinase C (PKC) in postmortem brain samples (Brodmann's areas 8 and 9) obtained from teenage suicide victims and control subjects. [3H]PDBU binding to PKC was determined in membranal and cytosolic fractions. We observed that Bmax of [3H]PDBU binding sites was significantly decreased in both membranal and cytosolic fractions in brain samples from Brodmann's areas 8-9 compared to matched controls. These results thus suggest that PKC may play a role in the pathophysiology of suicidal behavior.