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Biomedical subjects

H G Bernstein

Publications and source records attributed to H G Bernstein.

At least 37 records · Page 2Linked to original sources
PubMed1998

Schizophrenia and anteroventral thalamic nucleus: selective decrease of parvalbumin-immunoreactive thalamocortical projection neurons.

This study was designed to examine possible anatomical changes of thalamocortical circuits in schizophrenics. Previous immunocytochemical studies have shown that parvalbumin, a calcium-binding protein, occurs in thalamocortical projection neurons, but not in GABAergic interneurons in the anteroventral thalamic nucleus (AN). Using parvalbumin-immunocytochemistry we investigated the densities of thalamocortical projection neurons in the AN of schizophrenic cases (n = 12) and controls (n = 14). The densities of all neurons in the AN were estimated by Nissl-staining. The majority of thalamocortical projection neurons in AN were identified by parvalbumin-immunoreaction. Significantly reduced densities of thalamocortical projection neurons were estimated in the right (P = 0.003) and left AN (P = 0.018) in schizophrenic subjects. The densities of all neurons in right and left AN were also diminished in schizophrenics; however, these decreases did not reach statistical significance. The reductions of parvalbumin-positive thalamocortical projection neurons were not correlated with the length of disease, this finding supporting the neurodevelopmental etiology of structural abnormalities in schizophrenia.

Adult↗
PubMed1998

Cathepsin E immunoreactivity in human ocular tissues: influence of aging and pathological states.

We studied the antigenic expression of the aspartic proteinase cathepsin E in normal and pathologic human ocular tissues obtained from donors of different age. In the retina the enzyme was immunolocalized in neurons of outer and inner plexiform layers and in few ganglionic neurons. Muller cells were also sometimes immunoreactive for cathepsin E. An increase of neuronal enzyme immunoreactivity with age was evident. Immunocompetent blood cells invading the vitreous body were strongly immunostained for the enzyme. The enzyme is possibly involved in the retinal protein metabolism and might play immunological roles in certain pathologic events.

Adolescent↗
PubMed1998

Spermine/spermidine is expressed by retinal glial (Müller) cells and controls distinct K+ channels of their membrane.

There is recent evidence that polyamines such as spermine (spm) and spermidine (spd) may act as endogenous modulators of the activity of inwardly rectifying K+ channels. This type of K+ channels is abundantly expressed by retinal glial (Müller) cells where they are involved in important glial cell functions such as the clearance of excess extracellular K+ ions. This prompted us to study the following questions, i) do mammalian Müller cells contain endogenous spm/spd?; ii) do Müller cells possess the enzymes (e.g., ornithine decarboxylase, ODC) necessary to produce spm/spd?; and iii) does application of exogenous spm/spd exert specific effects onto inwardly rectifying K+ channels of Müller cells? Immunocytochemical studies were performed on histological sections of guinea-pig, rabbit, porcine, and human retinae, and on enzymatically dissociated Müller cells. Whole-cell and patch-clamp recordings were performed on enzymatically dissociated porcine and guinea-pig Müller cells. All above-mentioned questions could be answered with "yes." Specifically, the majority of Müller cells were labeled with antibodies directed to spm/spd, both within retinal sections and enzymatically isolated from retinal tissue. Müller cells in normal retinae express low levels of ODC but increase this expression markedly in cases of retinal pathology such as experimental epiretinal melanoma. Externally applied polyamines (1 mM) reduce (predominantly inward) whole-cell K+ currents, with the efficacies being spm > spd > put. If applied at the inside of membrane patches, spm (1 mM) blocks completely the outward currents through inwardly rectifying K+ channels but fails to affect the activity of large conductance, Ca2+-activated K+ channels. It is concluded that Müller cells contain endogenous channel-active polyamines, the synthesis of which may be up-regulated in pathological situations, and which may be involved in the control of both glial function and cell proliferation.

Adolescent↗
PubMed1998

Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease.

The search for the causes of neurodegenerative disorders is a major theme in brain research. Acquired disturbances of several aspects of cellular metabolism appear pathologically important in sporadic Alzheimer's disease (SDAT). Among these brain glucose utilisation is reduced in the early stages of the disease and the regulatory enzymes important for glucose metabolism are reduced. In the brain, insulin, insulin-like growth factors and their receptors regulate glucose metabolism and promote neuronal growth. To detect changes in the functional activity of the brain insulin neuromodulatory system of SDAT patients, we determined the concentrations of insulin and c-peptide as well as insulin receptor binding and IGF-I receptor binding in several regions of postmortem brain cortex during aging and Alzheimer's disease. Additionally, we performed immunohistochemical staining with antibodies against insulin in neocortical brain areas in SDAT and controls. We show for the first time that insulin and c-peptide concentration in the brain are correlated and decrease with aging, as do brain insulin receptor densities. Weak insulin-immunoreactivity could be demonstrated histochemically in pyramidal neurons of controls, whereas in SDAT a stronger insulin-immunoreactivity was found. On a biochemical level, insulin and c-peptide levels were reduced compared to middle-aged controls, but were unchanged compared to age-matched controls. Brain insulin receptor densities in SDAT were decreased compared to middle-aged controls, but increased in comparison to age-matched controls. IGF-I receptor densities were unchanged in aging and in SDAT. Tyrosine kinase activity, a signal transduction mechanism common to both receptor systems, was reduced in SDAT in comparison to middle-aged and age-matched control groups. These data are consistent with a neurotrophic role of insulin in the human brain and a disturbance of insulin signal transduction in SDAT brain and favor the hypothesis that insulin dependent functions may be of pathogenetic relevance in sporadic SDAT.

Adult↗
PubMed1998

Nitric oxide synthase-containing neurons in the human hypothalamus: reduced number of immunoreactive cells in the paraventricular nucleus of depressive patients and schizophrenics.

The neuroanatomical distribution of nitric oxide synthase-immunoreactive neurons was investigated in post mortem hypothalami of 10 patients suffering from schizophrenia, eight patients with depression and 13 matched control cases. Neuronal nitric oxide synthase containing nerve cells were detected in several hypothalamic nuclei including the medial preoptic region, the ventromedial, infundibular and suprachiasmatic nuclei and the lateral hypothalamus. The vast majority of hypothalamic nitric oxide synthase-immunoreactive neurons was found to be located in the paraventricular nucleus. Both magno and parvocellular paraventricular neurons contained the enzyme. A small subset of immunoreactive parvocellular paraventricular neurons co-expresses corticotropin-releasing hormone. The supraoptic nucleus did not contain nitric oxide synthase-immunoreactive neurons. Cell counts of paraventricular nitric oxide synthase-positive neurons in controls, schizophrenics and depressed patients revealed a statistically significant reduction of cell density in the right paraventricular nucleus of depressed patients and schizophrenics as compared to controls. The total amount of nitric oxide synthase-immunoreactive paraventricular neurons was smaller in depressive and schizophrenic patients than in normal cases. The putative pathophysiologic significance of the reduced expression of paraventricular nitric oxide synthase in depressive patients might be related to the supposed regulatory function of nitric oxide in the release of corticotropin-releasing hormone and arginine-vasopressin and/or oxytocin, which have been reported to be over-expressed in the so-called endogenous psychoses, especially in depression.

Adult↗
PubMed1998

Expression of hypothalamic peptides in mice lacking neuronal nitric oxide synthase: reduced beta-END immunoreactivity in the arcuate nucleus.

The gas nitric oxide (NO) is an important messenger in brain signaling. Along with many other functions, NO is thought to influence the expression and/or release of various hypothalamic hormones (corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH) and vasopressin). To learn more about the role of NO in neuroendocrine mechanisms, we studied in mutant mice lacking neuronal isoform of NO synthase (nNOS) the cellular expression of CRH, neurophysin (the carrier protein of vasopressin/oxytocin) and pro-opiomelanocortin (POMC), as well as of the POMC-derived peptides beta-endorphin (beta-END), alpha-melanocyte-stimulating hormone (alpha-MSH) and corticotropin (ACTH) by use of immunohistochemistry and in situ hybridization. Additionally, the remaining NO-generating capacities of the nNOS minus mice were investigated by NADPH-diaphorase histochemistry and citrulline immunohistochemistry as well as by immunohistochemical localization and Western blot analysis of endothelial NOS (eNOS) and nNOS isoforms. Amongst all hypothalamic peptides under investigation, only beta-END was found to be altered in mutant mice. A morphometric analysis of beta-END producing neurons of the arcuate nucleus revealed that significantly less cells were immunoreactive in mutant mice, whereas the expression of the precursor POMC as well as of other POMC-derived peptides was found to be unchanged. In addition to that, fewer beta-END-immunoreactive fibers were found in the paraventricular nucleus of nNOS minus mice in comparison to wild-type animals. Hence, the reduction of hypothalamic beta-END is probably a posttranslational event that might reflect a disturbed endorphinergic innervation of those hypothalamic neurons which normally express nNOS.

Animals↗
PubMed1998

Tissue distribution and subcellular localization of a G-protein activated phosphoinositide 3-kinase. An immunohistochemical study.

We studied by light-and electron microscopic immunohistochemical techniques the anatomical distribution and subcellular localization of a G-protein activated phosphoinositide 3-kinase gamma (PI3Kgamma) in several tissues of rat, mouse, dog and man. Using monospecific polyclonal antisera and monoclonal antibodies to the enzyme protein PI3Kgamma immunoreactivity was detected in rat and mouse neutrophils, prostate, kidney, exocrine pancreas, salivary glands (parotid gland) as well as in dog and human exocrine pancreas and parotid gland. No immunoreactive material was found in Langerhans islet cells and in the nervous tissue. Fine structural analysis of PI3Kgamma immunoreactivity revealed immunolabeling of the basolateral membrane of rat kidney tubular cells and certain cells in the parenchyma of the glandular part of rat prostate gland. Our morphological data suggest a possible involvement of the enzyme in cellular transport phenomena and a regulatory influence in secretory processes.

Animals↗
PubMed1996

Remarkable beta-endorphinergic innervation of human cerebral cortex as revealed by immunohistochemistry.

Beta-Endorphin immunoreactivity has been localized in 12 regions of the post mortem human cerebral cortex by using a polyclonal antiserum specifically recognizing the peptide. Cell bodies and proximal dendrites of certain cortical neurons (mostly interneurons) were densely populated with nerve endings immunoreactive for beta-endorphin. These 'endorphinoceptive' nerve cells were most abundantly present in the cingulate cortex as well as in the Gyri frontales superior and medius. In other cortical areas they appeared with much lower frequency (Gyri ambiens, semilunaris, parahippocampalis, temporalis). Our data show that the human cerebral cortex receives an endorphinergic innervation which might be of potential interest with regard to certain neuropsychiatric and neurodegenerative disorders.

Aged↗
PubMed1996

The possible place of cathepsins and cystatins in the puzzle of Alzheimer disease: a review.

Lysosomal proteinases (cathepsins) and their endogenous inhibitors (cystatins) have been found to be closely associated with senile plaques, cerebrovascular amyloid deposits, and neurofibrillary tangles in Alzheimer disease (AD). Further, profound changes in the lysosomal system seem to be an early event in "at-risk" neurons of AD brains. There is an ongoing controversy as to whether lysosome-associated proteolytic mechanisms are causally related to the development and/or further progression of the disease. The present article deals with some arguments "pro" and "contra" an involvement of the endosomal/lysosomal pathway in amyloidogenesis as a cardinal process in AD. Other putative targets of acidic proteinases and their natural inhibitors in the pathogenesis of AD (such as formation of neurofibrillary tangles and regulation of apolipoprotein E) are also discussed.

Alzheimer Disease↗
PubMed1995

Increased immunostaining for L-ornithine decarboxylase occurs in neocortical neurons of Alzheimer's disease patients.

We investigated the distribution of L-ornithine decarboxylase (ODC), an enzyme known to be involved in several developmental and restorative processes, in neocortical brain areas of Alzheimer's disease (AD) and normal patients by means of immunohistochemistry. While ODC immunoreactive material was only scarcely distributed in neocortical neurons of control brains, neocortical specimens from AD brains stood out by intense immunostaining for ODC. Dendrites and, to a lesser extent, axons of neurons from AD brains showed a strong immunoreaction to the enzyme, whereas neurons from non-affected brains displayed only a weak circumnuclear reaction pattern. Our results support the idea that neurorestorative processes take place in AD brains and that the ODC/polyamine system might be actively involved in this process.

Aged↗
PubMed1995

PTZ-kindling after colchicine lesion in the dentate gyrus of the rat hippocampus.

Pentylenetetrazol (PTZ)-kindling represents a model of a primarily generalized epilepsy. We investigated the role of the dentate gyrus of the hippocampus in this model of epilepsy by destruction of this structure by colchicine, injected in the dorsal and ventral hippocampus of rats. After a period of 7 days PTZ-kindling was started. The kindling development was slightly accelerated in colchicine treated animals compared to control rats. After kindling completion the learning performance of the rats was tested in a shuttle-box experiment. The learning deficit found in fully kindled rats was not influenced by colchicine pretreatment. However, colchicine itself impaired the learning performance of rats in the shuttle-box.

Animals↗
PubMed1994

An immunohistochemical study of cathepsin E in Alzheimer-type dementia brains.

We studied the immunohistochemical localization of cathepsin E (cath E) in the brains of patients with Alzheimer disease (AD) and control brains. In the normal brain cathepsin E immunoreactivity was detectable in a small number (below 5%) of neocortical and hippocampal neurons. In AD brains cathepsin E antigen was revealed in most large cortical and hippocampal pyramids and in neurons of the Nuc. basalis of Meynert. Cathepsin E was also present in cerebral microvessels, microglia, and in senile plaques. The enzyme might play roles in the process of neurodegeneration taking place in AD.

Aged↗
PubMed1994

Intracerebroventricular but not intraperitoneal administration of aluminum attenuates vasopressin-enhanced retrieval of a passive avoidance task in rats.

We studied the influence of single intracerebroventricular (ICV) and intraperitoneal (IP) injections of the neurotoxin aluminum on the retrieval of a passive avoidance task in rats and on the vasopressin-evoked improvement of the recall of the task. It was found that ICV administration of the metal alone strongly decreases the retention time of a passive avoidance task, whereas IP application of aluminum prolongs it. Vasopressin given ICV and IP leads to an enhancement of retrieval (prolongation of the retention time). Vasopressin in combination with aluminum does not improve the recall of the task when both substances are given ICV. Intraperitoneal injection of the neuropeptide together with the metal improves the recall of the task. Our data point to the crucial importance of the route of application of aluminum for behavioral studies.

Aluminum↗
PubMed1994

Cystatin A-like immunoreactivity is widely distributed in human brain and accumulates in neuritic plaques of Alzheimer disease subjects.

The cellular localization of cystatin A, an endogenously occurring inhibitor of lysosomal thiol proteases (cathepsins B, H, L and S), was studied immunohistochemically in human postmortem brain using the peroxidase-antiperoxidase method. Both polyclonal and monoclonal antibodies to cystatin A were employed. Western blot analysis revealed one molecular form of the inhibitor in human brain extracts. Its molecular weight was about 13,000. Immunostaining appeared in a sizeable population of neurons and a few cells surrounding cerebral blood vessels (pericytes). In Alzheimer disease subjects cystatin A was found in many neuritic plaques. Possible functional consequences with regard to a role of cystatin A in the inhibition of the Alzheimer amyloid precursor protein (APP)-clipping enzyme, cathepsin B, are discussed.

Aged↗
PubMed1994

Cathepsin L immunoreactivity in the hypothalamus of normal, streptozotocin-diabetic and vasopressin-deficient Brattleboro rats.

The immunolocalization of cathepsin L in the hypothalamus of normal rats was compared with the distribution of the enzyme in streptozotocin-treated animals and in vasopressin-deficient rats (Brattleboro strain). In rats with a normal metabolic status the neurons of magnocellular nucl. supraopticus and paraventricularis stood out by intense immunostaining for cathepsin L. In rats suffering from an experimentally induced diabetes mellitus and in homozygous Brattleboro rats we observed a strong reduction in enzyme immunoreactivity in these nuclei. Since cathepsin L is capable of splitting certain hypothalamic neuropeptides that are changed in diabetic animals, a role of the enzyme in the metabolism of these peptides is imaginable. Decrease in immunoreactive cathepsin L in vasopressin-deficient rats points to a possible involvement of the enzyme in the control of fluid homeostasis.

Animals↗
PubMed1993

Immunohistochemical demonstration of L-ornithine decarboxylase enzyme protein in different areas of the developing human brain.

L-Ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis and thus a unique marker of the proliferation and maturation processes, has been localized by means of immunohistochemistry in the human central nervous system. The enzyme protein has not only been found in the developing nervous system but also in the adult brain. The first immunopositive neuroblasts occurred in the 15th week of gravidity, whereas an increasing number of structures in the medulla oblongata and cerebellum showed ODC immunoreactivity in weeks 18-24 of gravidity. ODC immunoreactivity was revealed in multiple neurons and in the ependymal lining of ventricles. In the adult human brain ODC immunoreactivity was found in the hippocampus and in the spinal cord. In no case were immunoreactive glial cells observed.

Adolescent↗
PubMed1992

Hippocampal mossy fiber distribution does not correlate with two-way active avoidance performance in backcross lines derived from inbred mouse strains DBA/2 and C3H.

To elucidate the relation of genetically induced variations in two-way active avoidance performance and the extent of the hippocampal infra/intrapyramidal mossy fiber system (IIP-Mf) in inbred mouse strains DBA/2 (high performance, small IIP-Mf) and C3H (low performance, large IIP-Mf) we investigated a backcross line containing the DBA/2-derived genetic determinants for high avoidance performance in a C3H background. In the seventh backcross generation variations in performance analogous to the original strains were observed whereas the extent of mossy fibers was nearly homogeneous. This result suggests that both variables are determined by separate genetic factors at least in these strains and that differences in mossy fiber distribution are not an essential prerequisite for different active avoidance performance.

Afferent Pathways↗