The neuronal growth-associated protein GAP-43 (B-50, F1): neuronal specificity, developmental regulation and regional distribution of the human and rat mRNAs.

The protein that has been designated as GAP-43, B-50, F1 or pp46 is associated with the growth and modulation of neuronal connections. cDNA clones for the rat and human genes were isolated and used to demonstrate that the messenger RNA for the protein is expressed only in neurons, that its overall level is highest in the developing brain, and that in the adult human brain levels of the mRNA are highest in the associative neocortex.

An analysis of the arrangement of neurons in the cingulate cortex of schizophrenic patients.

A series of computer-assisted stereomorphometric analyses of the spatial arrangements of neurons and glia in postmortem cerebral cortex specimens has been developed and applied to both control subjects and schizophrenic patients. The data suggest that the anterior cingulate cortex of schizophrenic patients may contain domains or aggregates of neurons, particularly in layer II, which are smaller in size and separated by wider distances than those observed in the control group. Verification of the inferences made from the computer-generated data has been obtained by direct microscopic visualization and measurement of neuronal aggregates of layer II in Nissl-stained cingulate specimens from the control and schizophrenic groups.

Oxytocin in Alzheimer's disease: postmortem brain levels.

Oxytocin (OXY) injected into the hippocampus is reported to interfere with the formation of memory in experimental animals. Memory impairment is one of the distinguishing features of Alzheimer's disease. We have studied OXY immunoreactivity in postmortem brain tissue from 12 cases of histologically confirmed Alzheimer's disease and 13 controls.

Somatostatin and neuropeptide Y are unaltered in the amygdala in schizophrenia.

Although a biochemical abnormality has been postulated in the etiology of schizophrenia, evidence supporting this hypothesis has been conflicting. Because of the presence of somatostatin-like immunoreactivity (SLI) in limbic system nuclei of the brain, we examined postmortem concentrations of SLI in patients dying with schizophrenia and in normal controls. Concentrations of SLI in Brodmann cortical area 38, hippocampus, caudate, putamen, nucleus accumbens, and both segments of the globus pallidus were not significantly different from controls.

Maternal dietary NaCl intake influences weanling rats' salt preferences without affecting taste nerve responsiveness.

The present study examined the relationship between maternal dietary NaCl intake during the period from conception through weaning and weanling rats' elective consumption of salt; the study asked whether or not changes in offsprings' salt intake was mediated by altered taste responsiveness. The subjects were the 21-day-old offspring of 24 adult female rats fed diets containing .08% (low), 1% (mid), or 4% (high) NaCl from conception through weaning.

Human brain dopamine receptors in children and aging adults.

Since spontaneous oral dyskinesias are more prevalent in the elderly, and since these movements may be controlled by the balance of brain dopamine D1 and D2 dopamine receptors, we measured the densities of these receptors in 247 postmortem brain striata. In childhood, the densities of D1 and D2 dopamine receptors in the brain striatum rise and fall together. After age 20 years, D1 receptors disappear at 3.

Morphologic and histochemical characteristics of a spared subset of striatal neurons in Huntington's disease.

We have previously found that a biochemically distinct subset of neurons, containing nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), is selectively resistant to the degenerative process that affects the striatum in Huntington's disease (HD). We report the morphologic and histochemical characteristics of these striatal neurons and their distribution with respect to the histochemical compartments as defined by acetylcholinesterase (AChE) activity. Sections of striatum were stained histochemically for NADPH-d and AChE and immunocytochemically for somatostatin and neuropeptide Y-like immunoreactivity.

Alzheimer's disease: low cerebral somatostatin levels correlate with impaired cognitive function and cortical metabolism.

Somatostatin-like immunoreactivity in Alzheimer CSF was significantly lower than in that from age-matched controls. The degree of reduction correlated with indices of intellectual impairment and decline in cortical glucose utilization as determined by PET. There was a close association between reduction in CSF somatostatin and glucose hypometabolism in the parietal lobe.

Vasopressin in Alzheimer's disease: a study of postmortem brain concentrations.

Vasopressin (AVP) and its analogues are reported to improve learning- and memory-related performance in experimental animals, and perhaps also in humans. Memory impairment is a clinical hallmark of the dementing disorder, Alzheimer's disease. We have examined AVP concentrations in postmortem brain tissue from 12 patients with histologically confirmed Alzheimer's disease and 13 control subjects.

Topography of enkephalin, substance P and acetylcholinesterase staining in Huntington's disease striatum.

The distribution of Met-enkephalin (Enk) and substance P (SP) was examined in the striatum of Huntington's disease (HD) patients using immunoperoxidase techniques. Both Enk- and SP-like immunoreactivities (ir) were strikingly diminished in the dorsal caudate nucleus and putamen, while patchy staining persisted in the ventral putamen and nucleus accumbens. This was in sharp contrast to the patch-matrix pattern of acetylcholinesterase (AChE) staining which persisted throughout the entire striatum in HD.

A postmortem study of amino acid neurotransmitters in Alzheimer's disease.

Concentrations of putative neurotransmitter amino acids were measured in postmortem brains from 10 patients with Alzheimer's disease and 10 controls. Glutamate, aspartate, taurine, gamma-aminobutyric acid (GABA), and alanine levels were examined in 9 cortical regions, hippocampus, thalamus, and basal ganglia using high-performance liquid chromatography with electrochemical detection. There were no significant alterations in aspartate, taurine, or alanine levels in any of the regions examined.

Widespread reduction of somatostatin-like immunoreactivity in the cerebral cortex in Alzheimer's disease.

Although several studies have documented reduced concentrations of somatostatin-like immunoreactivity (SLI) in the cerebral cortex in Alzheimer's disease, there is controversy concerning the extent and importance of these changes. We measured SLI in brains obtained post mortem from 12 patients with pathologically confirmed Alzheimer's disease and from 13 neurologically normal controls. All major cortical and subcortical regions were examined.

Neuropeptide Y immunoreactivity is reduced in cerebral cortex in Alzheimer's disease.

Neuropeptide Y is a 36-amino acid peptide that is found in high concentrations in cerebral cortex and is contained in cortical neurons. We measured concentrations of this peptide in postmortem tissue from patients with Alzheimer's disease and controls using a sensitive and specific radioimmunoassay. High-performance liquid chromatography showed that more than 95% of immunoreactivity co-migrated with synthetic standards in both Alzheimer's disease and control frontal cortex.

Gilles de la Tourette's syndrome. A postmortem neuropathological and immunohistochemical study.

Immunocytochemical studies of the human forebrain have shown that enkephalin-like, dynorphin-like and substance-P-like immunoreactivity (respectively ELI, DLI, and SPI) normally present in unique pattern (now termed woolly fibers) in the globus pallidus and substantia nigra, in which their concentration is at its densest. Quantitative determinations moreover indicate that the levels of all 3 peptides are higher in the globus pallidus and substantia nigra than in any other region of the brain. We report here the distribution of immunoreactivity of these 3 peptides in the brain of a patient showing the typical clinical manifestations of Gilles de la Tourette's syndrome (TS); a disease for which no characteristic or consistent neuropathological features have been discerned.

Optimization of freezing, storage, and thawing conditions for the preparation of metabolically active synaptosomes from frozen rat and human brain.

Samples of rat and human cerebral cortex were frozen, stored, and thawed under a variety of conditions to define further the optimal procedure for storing human brain samples for subsequent metabolic and functional studies that use incubated synaptosomes. Tissue samples were best preserved by immersing them in isotonic sucrose prior to slow freezing, but there was no advantage in first chopping up the material. High concentrations of sucrose, rather than exerting a cryoprotective effect, were detrimental to subsequent synaptosomal performance (oxygen uptake, K+ accumulation, stimulus-induced release of amino acid neurotransmitters).

Somatostatin-28(1-12)-like immunoreactivity is reduced in Alzheimer's disease cerebral cortex.

A deficiency in somatostatin is the most consistently described neurochemical alteration in Alzheimer's disease (AD) attributable to intrinsic cortical neurons. Somatostatin-28 (SOM-28), an N-terminal-extended form of somatostatin, can be cleaved to form somatostatin-28(1-12)(SOM-28(1-12) ) and somatostatin-14 (SOM-14). We have measured concentrations of SOM-28(1-12)-like immunoreactivity in 8 cortical regions from 12 patients with AD and 13 controls.

Distribution of the molecular forms of acetylcholinesterase in human brain: alterations in dementia of the Alzheimer type.

Acetylcholinesterase (AChE), the enzyme that degrades acetylcholine, is a heterogeneous enzyme that can be separated into multiple molecular forms. A tetrameric membrane-bound form (G4) and a monomeric soluble form (G1) are the two predominant enzyme species in mammalian brain. The distribution of AChE molecular forms was defined by sucrose density gradients of 11 anatomical regions of postmortem brains from 10 patients with dementia of the Alzheimer type (DAT) and 14 nondemented controls of similar ages.

Brain choline acetyltransferase activity and neuropeptide Y concentrations in Alzheimer's disease.

Choline acetyltransferase (ChAT) activity and neuropeptide Y (NPY) levels in post-mortem tissues from patients with histologically proven Alzheimer's disease were compared with age-matched neurologically normal control individuals. Despite the high NPY concentrations in human cerebral cortex, no significant abnormalities were found. However, ChAT activity was reduced throughout the cortex, without a relationship to areas of functional deficit, as previously identified using fluorodeoxyglucose.

Maternal dietary sodium chloride levels affect the sex ratio in rat litters.

Eighty-eight adult female rats were fed diets containing either 0.08, 0.12, 1, 3, or 4% NaCl for at least one week prior to breeding and throughout gestation.

Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics.

Quantitative morphometric determinations of neuronal and glial density, neuron-glia ratios, and neuronal size were performed in the prefrontal, anterior cingulate, and primary motor cortex of ten controls and ten schizophrenics diagnosed by Feighner criteria under blind conditions to assess whether neuronal degeneration had occurred. Stepwise multiple regression and multiple classification analyses were used to evaluate the effect of potential confounding variables such as age, postmortem interval, fixation, hypoxia, and neuroleptic exposure on the measures studied. The neuronal density was significantly lower in layer VI of the prefrontal, layer V of the cingulate, and layer III of motor cortex.

Dietary salt affects fluid intake and output patterns of pregnant rats.

This study was done to determine how differences in dietary NaCl influence water and electrolyte balance during gestation. Eighteen adult female rats were fed diets containing either 0.12 (low), 1.

HPLC with electrochemical detection to measure chlorpromazine, thioridazine and metabolites in human brain.

Thirteen phenothiazine compounds were separated chromatographically using high performance liquid chromatography with coulometric electrochemical detection. These could be extracted from brain tissue using direct homogenization in tetrahydrofuran followed by one centrifugation, evaporation of supernatant and reconstitution in water. Fluphenazine was used as the internal standard.