Differential cellular expression of isoforms of inositol 1,4,5-triphosphate receptors in neurons and glia in brain

Inositol 1,4,5-trisphosphate receptors (IP3R) are mediators of second messenger-induced intracellular calcium release. Three isoforms are known to be expressed in brain, but their regional distributions and cellular localizations are little known. In order to better understand the roles of IP3 receptor isoforms in brain function, a first step is to define their distributions. We have used affinity-purified antibodies directed against peptides unique to each isoform to determine their sites of expression in rat brain. Type 1 IP3R (IP3R1) is dramatically enriched in Purkinje neurons in cerebellum and neurons in other regions, consistent with previous studies. By contrast, IP3R2 is only detected in glia, whereas IP3R3 is predominantly neuronal, with little detected in glia. IP3R3 is enriched in neuropil, especially in neuronal terminals (which often contain large dense core vesicles) in limbic and basal forebrain regions including olfactory tubercle, central nucleus of the amygdala, and bed nucleus of the stria terminalis. In addition, IP3R1 and IP3R3 have clearly distinct time courses of expression in developing brains. These data suggest separate roles for inositol 1,4,5-trisphosphate receptor isoforms in development, and for glial and neuronal function. The IP3R3 may be involved in regulation of neurotransmitter or neuropeptide release in terminals within specific nuclei of the basal forebrain and limbic system.     

Genetic analysis of three patients with an 18p- syndrome and dystonia

Some patients with an 18p- syndrome show dystonia, and a focal dystonia gene has been mapped to chromosome 18p. The authors evaluated the extent of the deletion in three patients with an 18p- syndrome and dystonia using 14 DNA markers on 18p. A common deleted area, covering the DYT7 locus, places the putative dystonia gene between the telomere of 18p and D18S1104 (49.6 cM). Dystonia in these patients may be caused by haploinsufficiency of the DYT7 gene, a new dystonia gene on 18p, or may result from developmental brain anomalies.     

Methamphetamine administration causes overexpression of nNOS in the mouse striatum

The accumulated evidence suggests that the overproduction of nitric oxide (NO) is involved in methamphetamine (METH)-induced neurotoxicity. Using NADPH-diaphorase histochemistry, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) antibody immunohistochemistry, the possible overexpression of nNOS and iNOS was investigated in the brains of mice treated with METH. The number of positive cells or the density of positive fibers was assessed at 1 h, 24 h and 1 week after METH injections. There were no clear positive iNOS cells and fibers demonstrated in the brains of mice after METH treatment. In contrast, METH caused marked increases in nNOS in the striatum and hippocampus at 1 and 24 h post-treatment. The nNOS expression normalized by 1 week. There were no statistical changes in nNOS expression in the frontal cortex, the cerebellar cortex, nor in the substantia nigra. These results provide further support for the idea that NO is involved in the neurotoxic effects of METH.     

Cognitive Behavioral Therapy of Minor Depressive Symptoms in Elderly Chinese Americans: A Pilot Study

There is a high prevalence of suicide amongelderly Chinese, and particularly among elderly Chinesewomen in Mainland China with a prevalence of 19.6 perhundred thousand. Since Chinese individuals may much more highly value education, acognitive-behavioral package originated by RicardoMunoz, Ph.D. was adapted for Chinese American subjects.The material was videotaped in eight sessions,approximately 25 minutes in length, to be shown to communitysubjects who were at least 40 years and over. Inaddition, a videotape of muscular relaxation techniqueswas made. A manual written in Chinese about the content of each class, was given to each subject whenhe/she attended. The experimental group showedsignificant improvement in the scores in the HamiltonDepression Scale, including the Somatic Subscale in the Hamilton Anxiety Scale. There was nosignificant improvement in the control group on any ofthe measures. Thus the study suggests the efficacy ofpsychoeducational classes in reducing symptoms ofdepression in non-patient community elderly. Other studiesare being conducted among Korean Americans and JapaneseAmericans in the United States, and also in the Orientamong Japanese elderly.     

Mild experimental brain injury differentially alters the expression of neurotrophin and neurotrophin receptor mRNAs in the hippocampus

The molecular events responsible for impairments in cognition following mild traumatic brain injury are poorly understood. Neurotrophins, such as brain-derived neurotrophic factor (BDNF), have been identified as having a role in learning and memory. We have previously demonstrated that following experimental brain trauma of moderate severity (2.0-2.1 atm), mRNA levels of BDNF and its high-affinity receptor, trkB, are increased bilaterally in the hippocampus for several hours, whereas NT-3 mRNA expression is decreased. In the present study, we used in situ hybridization to compare BDNF, trkB, NT-3, and trkC mRNA expression in rat hippocampus at 3 or 6 h after a lateral fluid percussion brain injury (FPI) of mild severity (1.0 atm) to sham-injured controls at equivalent time points. Mild FPI induced significant increases in hybridization levels for BDNF and trkB mRNAs, and a decrease in NT-3 mRNA in the hippocampus. However, in contrast to the bilateral effects of moderate experimental brain injury, the present changes with mild injury were restricted to the injured side. These findings demonstrate that even a mild traumatic brain injury differentially alters neurotrophin and neurotrophin receptor levels in the hippocampus. Such alterations may have important implications for neural plasticity and recovery of function in people who sustain a mild head injury.     

Prevention of stroke in urban China: a community-based intervention trial

BACKGROUND AND PURPOSE: Stroke has been the second leading cause of death in large cities in China since the 1980s. Meanwhile, the prevalences of hypertension and smoking have steadily increased over the last 2 decades. Therefore, a community-based intervention trial was initiated in 7 Chinese cities in 1987. The overall goal of the study was to evaluate the effectiveness of an intervention aimed at reducing multiple risk factors for stroke. The primary study objective was to reduce the incidence of stroke by 25% over 3.5 years of intervention. METHODS: In May 1987 in each of 7 the cities, 2 geographically separated communities with a registered population of about 10 000 each were selected as either intervention or control communities. In each community, a cohort containing about 2700 subjects (>/=35 years old) free of stroke was sampled, and a survey was administered to obtain baseline data and screen the eligible subjects for intervention. In each city, a program of treatment for hypertension, heart disease, and diabetes was instituted in the intervention cohort (n approximately 2700) and health education was provided to the full intervention community (n approximately 10 000). A follow-up survey was conducted in 1990. Comparisons of intervention and control cohorts in each city were pooled to yield a single summary. RESULTS: A total of 18 786 subjects were recruited to the intervention cohort and 18 876 to the control cohort from 7 cities. After 3.5 years, 174 new stroke cases had occurred in the intervention cohort and 253 in the control cohort. The 3.5-year cumulative incidence of total stroke was significantly lower in the intervention cohort than the control cohort (0.93% versus 1.34%; RR=0.69; 95% CI, 0.57 to 0.84). The incidence rates of nonfatal and fatal stroke, as well as ischemic and hemorrhagic stroke, were significantly lower in the intervention cohort than the control cohort. The prevalence of hypertension increased by 4.3% in the intervention cohort and by 7.8% in the control cohort. The average systolic and diastolic blood pressures increased more in the control cohort than in the intervention cohort. Among hypertensive individuals in the intervention cohort, awareness of hypertension increased by 6.7% and the percentage of hypertensives who regularly took antihypertensive medication increased 13.2%. All of these indices became worse in the control cohort. The prevalence of heart diseases and diabetes increased significantly in the both cohorts (P<0.01). The prevalence of consumption of alcohol increased slightly, and that of smoking remained constant in both cohorts. CONCLUSIONS: A community-based intervention for stroke reduction is feasible and effective in the cities of China. The reduction, due to the intervention, in the incidence of stroke in the intervention cohort was statistically significant after 3.5 years of intervention. The sharp reduction in the incidence of stroke may be due to the interventions having blunted the expected increase in hypertension that accompanies aging as well as to better and earlier treatment of hypertension, particularly borderline hypertension. Applied health education to all the residents of the community may have prevented some normotensive individuals from developing hypertension and improved overall health awareness and knowledge.     

Physics and the quandaries of contemporary psychiatry: review and research

Although in physics, quantum mechanical principles have long replaced Newtonian ones, we continue to apply the latter in models of the mind and its diseases. This article discusses the possible theoretical application of quantum principles to mind-brain function. Empirically, this study tested which of these principles practicing psychiatrists found more applicable in clinical practice. Psychiatrists (N = 382) at universities around the United States were asked to answer a questionnaire that contained clinical scenarios reflecting mental, interpersonal, or therapeutic processes corresponding to quantum or classical physical principles. Respondents (N = 191) were significantly more likely to rate scenarios reflecting quantum principles as being consistent with their experience than they were those reflecting classical principles (p < .0005). This effect was significantly greater in more experienced psychiatrists. Quantum physics, a powerful tool in understanding properties of both micro- and macro-level phenomena, may have implications at the human level, invoking the roles of observer, interpersonal relationships, and resources such as resiliency and creativity.     

Opposite links of positive and negative symptomatology with memory errors in schizophrenia

We wished to confirm and extend a previous correlational study of our group, suggesting that positive symptoms in schizophrenia were linked to an increase in certain types of memory errors, and negative symptoms to a decrease in other types of errors. A post-hoc analysis was conducted in 33 schizophrenic patients and 40 normal control subjects on memory errors collected in a free recall task and two types of recognition tasks. The memory errors were intrusions and list errors in free recall, and decision bias towards false alarms in recognition, all assumed to reflect a source-monitoring failure. In a first analysis, the patient sample was split along the median for positive symptoms as rated by the Scale for the Assessment of Positive Symptoms (SAPS). In a second analysis, it was split along the median for negative symptoms as rated by the Scale for the Assessment of Negative Symptoms (SANS). Patients with high ratings of positive symptoms made more memory errors (intrusions, list errors, false alarms) than those with low ratings, supporting the hypothesis of a link between positive symptomatology and source-monitoring failure. On the other hand, patients with high ratings of negative symptoms made fewer of these errors than the other patients. Fewer errors were specifically associated with more affective flattening, alogia and anhedonia, whereas avolition was entirely unrelated to them.     

Influence of fetal to neonatal transition on nitric oxide synthase expression in the nucleus tractus solitarius in sheep

Transition from fetal to newborn life is accompanied by a marked rise in circulating norepinephrine (NE) concentrations though arterial blood pressure does not substantively change. Nitric oxide (NO) plays an important role in the central regulation of sympathetic tone in the nucleus tractus solitarius (NTS) and neuronal NO synthase (nNOS) expression is functionally regulated in the brain. The purpose of these studies was to determine the influence of transition at birth on nNOS expression in the brainstem nuclei, particularly in the NTS, associated with changes in arterial pressure and plasma NE concentration. Experiments were performed using time-dated gestational ewes with twin fetuses. Arterial blood pressure was recorded and arterial blood NE concentrations were measured in the term fetus (gestational 147-148 days) and newborn lambs (4 h of postnatal age). The fetal and newborn animals were then perfused with 4% paraformaldehyde. Sections of the medulla were examined by using both immunolabeling with a polyclonal antibody directed against nNOS and nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) histochemistry, a marker for expression of nNOS. Micrographs were quantified using a microscope with reticule grid to measure the number of positive cells containing color staining in the brainstem nuclei. Plasma NE concentration in the newborn was more than two-fold greater compared to fetal values but mean arterial blood pressure was similar between fetus and newborn. The nNOS positive cells and NADPHd positive cells were significantly increased in the medial NTS (mNTS) of the newborn compared to fetus. nNOS immunoreactivity and NADPHd reactivity tended to increase in the rostral ventral medulla (RVM) in newborn, but were not altered in other brainstem nuclei during the transition from fetal to newborn life. The results suggest that nNOS expression in the mNTS is predominately enhanced at 4 h of neonatal age vs. the term fetus. We conclude that elevated circulating NE is associated with up-regulation of nNOS in the mNTS which may serve a protective role in central regulation of neonatal arterial blood pressure.     

Genetics of primary dystonia

Currently, at least 12 types of dystonia can be distinguished on a genetic basis. Advances in the molecular genetics of dystonia have led to the recent identification of a 3-bp deletion in the DYT1 gene, causing early-onset generalized torsion dystonia (TD), and to the detection of mutations in the GTP cyclohydrolase I and the tyrosine hydroxylase genes causing dopa-responsive dystonia (DYT5). A missense change in the D2 dopamine receptor has been shown to be associated with myoclonus-dystonia in one family. In addition, six other dystonia gene loci have been mapped to chromosomal regions, including a locus for a mixed dystonia phenotype (DYT6), one form of focal dystonia (DYT7), two types of paroxysmal dystonia (DYT8, DYT9), X-linked dystonia-parkinsonism (DYT3), and rapid-onset dystonia parkinsonism (DYT12). No positive linkage studies have as yet been reported for autosomal recessive TD (DYT2) and in several other large families with various types of dominantly inherited TD (DYT4). It may be anticipated that the traditional clinical and etiological classifications of dystonia will increasingly be replaced by a genetic one and that the identification of more dystonia genes may lead to a better understanding of these largely nondegenerative disorders.