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Binding of double stranded oligonucleotide probes for particular transcription factors with leucine-zipper motifs in discrete brain structures of mice with acquired and inherent spontaneous seizures.

Nuclear extracts of mouse brain contained binding of radiolabeled oligonucleotide probes for particular transcription factors with leucine-zipper motifs including activator protein-1 (AP1), cyclic AMP response element binding protein (CREB) and c-Myc. An acute intraperitoneal injection of pentylenetetrazole (PTZ) at a convulsive dose significantly potentiated binding of the probe for AP1 in the cerebral cortex, hippocampus, striatum, hypothalamus and midbrain, without affecting that in the medulla-pons and cerebellum, 2 h after the administration. However, PTZ failed to affect binding of the probe for CREB under the similar experimental conditions. In contrast, PTZ induced a slight but statistically significant decrease in binding of the AP1 probe in the cerebellum, without altering that in the hippocampus, 14 h after the injection. On the other hand, repeated administration of PTZ at a subconvulsive dose led to spontaneous kindling seizures in animals, with a concomitant decrease in binding of the AP1 probe in both the hippocampus and cerebellum. In contrast to these animals with acquired spontaneous seizures, however, binding of the AP1 probe was significantly higher in three different telencephalic structures of inherently spontaneous epileptic El mice than that in the parent ddY mice, with binding of probes for CREB and c-Myc being unchanged. These results suggest that different molecular mechanisms may underlie the expression of being unchanged. These results suggest that different molecular mechanisms may underlie the expression of AP1 in discrete brain structures of mice with acquired and inherent spontaneous seizures.

Activating Transcription Factor 2↗

Dietary soy phytoestrogen effects on brain structure and aromatase in Long-Evans rats.

Phytoestrogens are estrogen-like (plant-derived) molecules that protect against age-related diseases (cardiovascular disease and osteoporosis), hormone-dependent (breast and prostate) cancers and selectively bind estrogen receptors. However, little is known about the influence of phytoestrogens on brain. Using diets containing either high phytoestrogen levels, derived from soy, or very low phytoestrogens we quantified phytoestrogen concentrations of daidzein, genistein and equol in brain. We found that dietary phytoestrogens: significantly decrease body and prostate weights, do not alter brain aromatase levels and significantly change during adulthood the structure of the sexually dimorphic brain region (i.e. anteroventral periventricular nucleus; AVPV) in male, but not in female rats. Since most commercial animal diets contain significant concentrations of phytoestrogens their influence on brain structure should be considered.

Animals↗

Impact of normal sexual dimorphisms on sex differences in structural brain abnormalities in schizophrenia assessed by magnetic resonance imaging.

BACKGROUND: Previous studies suggest that the impact of early insults predisposing to schizophrenia may have differential consequences by sex. We hypothesized that brain regions found to be structurally different in normal men and women (sexual dimorphisms) and abnormal in schizophrenia would show significant sex differences in brain abnormalities, particularly in the cortex, in schizophrenia. METHODS: Forty outpatients diagnosed as having schizophrenia by DSM-III-R were systematically sampled to be comparable within sex with 48 normal comparison subjects on the basis of age, ethnicity, parental socioeconomic status, and handedness. A comprehensive assessment of the entire brain was based on T1-weighted 3-dimensional images acquired from a 1.5-T magnet. Multivariate general linear models for correlated data were used to test for sex-specific effects regarding 22 hypothesized cortical, subcortical, and cerebrospinal fluid brain volumes, adjusted for age and total cerebrum size. Sex x group interactions were also tested on asymmetries of the planum temporale, Heschl's gyrus, and superior temporal gyrus, additionally controlled for handedness. RESULTS: Normal patterns of sexual dimorphisms were disrupted in schizophrenia. Sex-specific effects were primarily evident in the cortex, particularly in the frontomedial cortex, basal forebrain, cingulate and paracingulate gyri, posterior supramarginal gyrus, and planum temporale. Normal asymmetry of the planum was also disrupted differentially in men and women with schizophrenia. There were no significant differential sex effects in subcortical gray matter regions or cerebrospinal fluid. CONCLUSION: Factors that produce normal sexual dimorphisms may be associated with modulating insults producing schizophrenia, particularly in the cortex.

Adult↗

Effects of adverse experiences for brain structure and function.

Studies of the hippocampus as a target of stress and stress hormones have revealed a considerable degree of structural plasticity in the adult brain. Repeated stress causes shortening and debranching of dendrites in the CA3 region of the hippocampus and suppresses neurogenesis of dentate gyrus granule neurons. Both forms of structural remodeling of the hippocampus appear to be reversible and are mediated by glucocorticoid hormones working in concert with excitatory amino acids (EAA) and N-methyl-D-aspartate (NMDA) receptors, along with transmitters such as serotonin and the GABA-benzodiazepine system. Glucocorticoids, EAA, and NMDA receptors are also involved in neuronal damage and death that is caused in pyramidal neurons by seizures and by ischemia. A similar mechanism may be involved in hippocampal damage caused by severe and prolonged psychosocial stress. Studies using magnetic resonance imaging have shown that there is a selective atrophy of the human hippocampus in a number of psychiatric disorders, as well as during aging in some individuals, accompanied by deficits in declarative, spatial, and contextual memory performance. It is therefore important to appreciate how hippocampal dysfunction may play a role in the symptoms of the psychiatric illness and, from a therapeutic standpoint, to distinguish between a permanent loss of cells and a reversible remodeling to develop treatment strategies to prevent or reverse deficits. Remodeling of the hippocampus may be only the tip of the iceberg; other brain regions may also be affected.

Adult↗

The spectrum of structural brain changes in schizophrenia: age of onset as a predictor of cognitive and clinical impairments and their cerebral correlates.

A range of cerebral structures was assessed in a series of 172 CT scans of groups of psychiatric patients (including 101 in-patients with chronic schizophrenia) and related to assessments of clinical state and psychological function. Ventricular indices were increased in patients with schizophrenia by comparison with patients with other psychiatric disorders: brain area, which is modestly positively correlated with ventricular indices, was significantly (P less than 0.01) reduced in patients with schizophrenia. Among in-patients with chronic schizophrenia, measures of increased ventricular size were significantly associated with impaired social behaviour and with movement disorder. Memory for famous names in the distant past (a test of remote memory) was the only psychological test which showed significant associations with indices of ventricular size; this suggests that ventricular enlargement and its psychological sequelae occur relatively early in the disease process. Dichotomization of the sample of schizophrenic patients around the mean age of onset revealed that a range of clinical and psychological functions are significantly more abnormal in those with an early age of onset than in those in whom the onset was later. Early onset cases also perform less well academically and occupationally before illness onset. Within the early onset group some significant correlations between cognitive function and brain area were seen. The findings suggest that: (i) some at least of the structural changes in schizophrenia arise at a time when the brain is still developing; and (ii) age of onset is an important determinant of social and intellectual impairment and is relevant to the relationship between brain structure and cognitive deficits.

Bipolar Disorder↗

Peptides from bovine brain: structure and biological role.

Fractionation of bovine brain extracts followed by automatic Edman sequencing of individual components resulted in identification of 107 endogenous peptides formed from functional proteins (haemoglobin, myelin basic protein, cytochrome c oxidase, etc) or unknown precursors. Several of the newly identified brain peptides demonstrate different types of biological activity; some of the substances show considerable overlap with the known biologically active peptides. It is suggested that these peptides should participate in regulation of extracellular and intracellular biochemical processes. A concept of 'tissue-specific peptide pool' is formulated describing a novel system of peptidergic regulation, complementary to the conventional hormonal and neuromodulatory systems. According to that description functional proteins provide their proteolytically derived fragments for maintaining the tissue homeostasis by modulating the availability of peptide receptors to respective 'true' ligands.

Amino Acid Sequence↗