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New and revised data on volumes of brain structures in insectivores and primates.

More than 2,000 data on volumetric measurements of 42 structures in a variety of up to 76 species (28 insectivores, 21 prosimians, 27 simians) are given. All volumes measured in serial sections were converted to fresh volumes of a brain having a standard size within a given species. The date are available to all scientists for comparison and analysis. To allow critical evaluation, details on fixation and preparation, on determination of fresh brain weights and volumes of brain parts and on intraspecific variability are given.

Animals↗

Detection and mapping of abnormal brain structure with a probabilistic atlas of cortical surfaces.

PURPOSE: We have devised, implemented, and tested a technique for creating a comprehensive probabilistic atlas of the human cerebral cortex, based on high-dimensional fluid transformations. The goal of the atlas is to detect and quantify subtle and distributed patterns of deviation from normal cortical anatomy, in a 3D brain image from any given subject. METHOD: Given a 3D MR image of a new subject, a high-resolution surface representation of the cerebral cortex is automatically extracted. The algorithm then calculates a set of high-dimensional volumetric maps, fluidly deforming this surface into structural correspondence with other cortical surfaces, selected one by one from an anatomic image database. The family of volumetric warps so constructed encodes statistical properties of local anatomical variation across the cortical surface. Additional strategies are developed to fluidly deform the sulcal patterns of different subjects into structural correspondence. A probability space of random transformations, based on the theory of anisotropic Gaussian random fields, is then used to encode information on complex variations in gyral and sulcal topography from one individual to another. A complete system of 256(2) probability density functions is computed to reflect the observed variability in stereotaxic space of the points whose correspondences are found by the warping algorithm. Confidence limits in stereotaxic space are determined for cortical surface points in the new subject's brain. RESULTS: Color-coded probability maps are generated, which highlight and quantify regional patterns of deformity in the anatomy of new subjects. These maps indicate locally the probability of each anatomic point being as unusually situated, given the distributions of corresponding points in the scans of normal subjects. 3D MRI volumes are analyzed, from subjects with clinically determined Alzheimer disease and age-matched normal subjects. CONCLUSION: Applications of the random fluid-based probabilistic atlas include the transfer of multisubject 3D functional, vascular, and histologic maps onto a single anatomic template, the mapping of 3D atlases onto the scans of new subjects, and the rapid detection, quantification, and mapping of local shape changes in 3D medical images in disease and during normal or abnormal growth and development.

Aged↗

Rapid potentiation of DNA binding activities of particular transcription factors with leucine-zipper motifs in discrete brain structures of the gerbil with transient forebrain ischemia.

Binding of radiolabeled double stranded oligonucleotide probes for nuclear transcription factors with leucine-zipper motifs, such as activator protein-1 (AP1), cyclic AMP response element binding protein (CREB) and Myc, was unevenly distributed in gerbil brain in a manner peculiar to each factor. Among 3 different hippocampal subfields examined, the dentate gyrus had the highest basal DNA binding activities of AP1 with progressively less potent binding in the CA3 and CA1 subfields. Similarly, the dentate gyrus was highest in the basal binding of probes for both CREB and Myc among the 3 distinct hippocampal subregions. However, transient forebrain ischemia for 5 min induced more potent enhancement of the AP1 binding in the CA1 subfield 4 h after the insult than in the CA3 subfield and dentate gyrus. In contrast, the ischemic injury similarly tripled DNA binding activities of CREB without markedly affecting those of Myc in hippocampal CA1 and CA3 subfields. Binding of the probe for AP1 was also markedly potentiated following ischemia in the thalamus, caudate putamen, frontal cortex and cerebellar cortex in a rank order of decreasing magnitude, while the ischemic insult induced slight but statistically significant potentiation of both CREB and Myc binding in the thalamus without affecting that in other discrete brain regions. These results suggest that expression of AP1 may be a determinant of unique vulnerability and/or resistance to an ischemic insult in the gerbil hippocampus.

Animals↗

Serotonin and norepinephrine content in brain structures of rats with experimental and transplantation-compensated diabetes.

The development of alloxan-induced diabetes in rats is shown to be accompanied by a decrease in the norepinephrine (NE) and serotonin (5-OT) content in the neocortex and caudal segment of the brain stem. Simultaneously the intensity of 3H-leucine labelling of the brain tissue was decreased. The attempt to compensate the diabetic syndrome in rats by transplanting the embryonic pancreas (EP) into the anterior chamber of the eye (ACE) was successful. All the animals with the adapted transplant showed a return of the monoamine level to the normal, a decrease in urine glucose, as well as normalization of protein synthesis by the 14th-20th days.

Alloxan↗

Differences between brain structures in nuclear translocation and DNA binding of the glucocorticoid receptor during stress and the circadian cycle.

Glucocorticoid receptors (GRs) are transcription factors that, upon activation by glucocorticoids, translocate to the cell nucleus, and bind to specific response elements (GREs) in the promoter region of target genes. We analysed stress- and circadian-induced changes in nuclear translocation and GRE binding of GRs in the hippocampus and the prefrontal cortex of the rat brain. Nuclear translocation and binding to GRE were measured in nuclear extracts by Western blot and gel shift, respectively. When glucocorticoid levels were low, as during the light period of the circadian cycle, nuclear GRs and GRE binding were almost undetectable. However, the increase in glucocorticoid levels observed during the dark phase of the circadian cycle or after stress induced a massive nuclear translocation of GRs and GRE binding. These effects were corticosterone-dependent because they were suppressed by adrenalectomy and restored by the injection of corticosterone. Furthermore, GR translocation and GRE binding were of higher amplitude or lasted longer in the hippocampus than in the prefrontal cortex. By contrast, extracellular levels of glucocorticoids, measured by microdialysis in freely moving animals, were identical in the two structures. These results suggest that specific intracellular regulations of GR activity contribute to differentiate the effects of glucocorticoids in different regions of the brain.

Active Transport, Cell Nucleus↗

Presurgical assessment of memory-related brain structures: the Wada test and functional neuroimaging.

Medial temporal lobe structures are known to play a major role in memory processing. Recent work has revealed that extratemporal structures (e.g. the frontal lobe and thalamus) may also be important in memory function. In candidates for epilepsy surgery, particularly in those with temporal lobe seizures, presurgical evaluation of memory function is essential, since seizures may originate in the neural substrate that is critical for memory. In this article, we review the tools used for presurgical evaluation and their contribution to the understanding of memory function, focusing on the Wada test, [18F]fluorodeoxy-glucose positron emission tomography ([18F]FDG-PET) and functional magnetic resonance imaging (fMRI). We also explore perspectives on future studies that may elucidate the role of the temporal and extratemporal structures in memory function and the mechanisms of cerebral plasticity.

Brain↗

Distribution of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylglycol (DOPEG) in microdissected brain structures and the pituitary gland: metabolite changes in the median eminence in response to hyperprolactinemia and suckling.

Dopamine (DA), norepinephrine (NE), epinephrine (E), 3,4-dihydroxyphenylglycol (DOPEG) and dihydroxyphenylacetic acid (DOPAC) were determined simultaneously by a radioenzymatic, thin-layer chromatographic assay able to detect 1-10 pg of the parent compounds and 80-120 pg of their metabolites. A localization study of these compounds in 20 micro-dissected hypothalamic and limbic structures and the anterior and posterior pituitary glands of male rats was completed. DOPAC was detectable in 14 of 22 structures with the lowest DOPAC/DA ratio being found in the caudate nucleus (7.1%) and the highest in the medial aspect of the ventromedial nucleus of the hypothalamus (422.0%). There was a higher DOPAC/DA ratio in the lateral (21.5%) than in the medial (11.3%) portion of the median eminence suggesting that a greater portion of released DA in the medial median eminence enters the portal circulation. DOPEG was detectable in 6 of 22 structures with DOPEG/NE ratios ranging from 8% (interstitial nucleus of the stria terminalis, ventral aspect) to 32% (medial median eminence). A poor correlation exists between DOPAC and DA concentrations in the various brain regions while there was a stronger relationship between DOPEG and NE concentrations. Male rats were rendered hyper-prolactinemic for 48 hours with injections of ovine prolactin (oPRL) every 8 hours (4 mg/kg body weight sc). In such rats there was a suppression of endogenous rat PRL (rPRL) secretion, the DOPAC/DA ratio increased 2.2-fold in the medial (MEm) and 1.9-fold in the lateral median eminence (MEl), and the DA concentration in the anterior pituitary also increased 2.6-fold. In 10 day postpartum lactating rats, suckling produced marked increases in serum rPRL but no change in DOPAC/DA ratios in the ME or in the DA concentration in the anterior pituitary. The data reveal a wide range of DOPAC/DA ratios (7-422%) in brain regions containing cell bodies, axons and terminals of the different dopaminergic neuronal tracts in brain and pituitary. Considering the DOPAC/DA ratios in the MEm and MEl, it is suggested that a large perturbation of dopaminergic transmission produces a significant ratio change while a smaller perturbation is not detected by this index of neuronal metabolism.

3,4-Dihydroxyphenylacetic Acid↗

Characterization of beta-endorphin-immunoreactivity in limbic brain structures of rats self-administering heroin or cocaine.

The effects of intravenous self-administration of 30 micrograms infusions of either heroin or cocaine, or saline on the concentrations of beta-endorphin-immunoreactivity (beta E-IR) in the anterior part of the rat brain limbic system were studied. Self-administration of heroin and cocaine for 5 daily sessions resulted in a marked reduction of the concentrations of beta E-IR in the nucleus accumbens, rostral striatum, septum and hippocampus at the time of the scheduled next session on day 6. In pooled extracts of these regions from rats receiving saline, combined application of high-pressure liquid chromatography (HPLC) fractionation and specific radioimmunoassays revealed the presence of a number of beta E-related peptides co-chromatographing with synthetic non-acetylated and acetylated alpha, beta- and gamma-type endorphins. Similar profiles were found after HPLC fractionation of extracts of these regions from rats self-administering heroin and cocaine. Rats self-administering heroin or cocaine, however, showed decreased amounts of all detected forms of beta-endorphin as compared to saline rats. These findings indicate that both self-administration of an opiate that induces psychic as well as physical dependence and of a non-opiate stimulant inducing psychic but not physical dependence, results in a significant decrease of beta E and related peptides in limbic brain regions of the rat. All forms of beta E detected after HPLC were equally affected, suggesting an overall effect of the drugs on peptide turnover. These results suggest that beta E and related peptides may be involved in the neurochemical mechanisms underlying psychic dependence to drugs.

Animals↗

Role of neonatal androgens in sexual differentiation of brain structure, scent marking, and gonadotropin secretion in gerbils.

Gerbils display a sexually dimorphic scent marking behavior that responds to testosterone (T) in adulthood and develops under the influence of testosterone perinatally. A complex of cell groups between the preoptic area and anterior hypothalamus of the gerbil brain is also sexually dimorphic and responsive to testosterone. One of these cell groups, the sexually dimorphic area pars compacta (SDApc), usually exists only in males. Even when given testosterone, adult female gerbils rarely have an SDApc. To determine if the SDApc develops under the influence of testosterone, male gerbils were castrated or given sham operations on the day they were born or 1 day later, or were not manipulated. Female gerbils were injected subcutaneously with 0, 50, or 100 micrograms testosterone propionate (TP) on the day after birth. When given ovarian transplants as adults, neonatally castrated males scent marked at low levels typical of females. Neonatally androgenized females given testosterone as adults scent marked at high levels typical of males. Neonatal castration did not affect the probability that the SDApc would develop, but neonatal androgenization did. Half the females given either dose of TP as neonates had SDApcs bilaterally. The sizes of the SDApcs present in females depended on the dose of testosterone given neonatally. The larger dose produced larger SDApcs. The 100-micrograms dose of TP also defeminized gonadotropin secretion, but the 50-micrograms dose did not. The castration of males neonatally prevented the defeminization normally caused by endogenous testosterone. Both groups of neonatally castrated males formed corpora lutea in their ovarian transplants, but control males did not.

Animals↗