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M Jucker

Publications and source records attributed to M Jucker.

At least 55 records · Page 3Linked to original sources
PubMed1993

Localization of a laminin-binding protein in brain.

A 110,000 mol.wt laminin-binding protein from newborn mouse brain recognizes a neurite promoting laminin A chain site and is related to the beta-amyloid precursor protein. In the present study, we examined the expression of 110,000 mol.wt laminin-binding protein in brains of adult mice, rats, and non-human primates. Essentially identical immunoreactivities were observed across species with distinct staining of cortical pyramidal neurons with apical dendrites, cerebellar basket cell axons, hippocampal mossy fibers, and fine labeling of processes throughout the brain. Colocalization of immunoreactivities to 110,000 mol.wt laminin-binding protein and to laminin in neurons of the adult rat brain was observed. Electron microscopy demonstrated that 110,000 mol.wt laminin-binding protein-like immunoreactivity is intracellular and is possibly associated with the neuronal cytoskeleton. Western blot analysis revealed that anti-110,000 mol.wt laminin-binding protein also recognizes a 140,000 mol.wt protein in the pellet, in addition to the 110,000 mol.wt protein in the Triton soluble extract. Antibody fractions specific to the two reactive protein species (110,000 mol.wt and 140,000 mol.wt) exhibited cross-reactivity on immunoblots and revealed similar immunohistochemical staining in adult brain. Results suggest a significant interaction between laminin-like molecules and 110,000 mol.wt laminin-binding protein-like molecules in normal brain function, in response to CNS injury and possibly in the pathogenesis of Alzheimer's disease.

Amino Acid Sequence↗
PubMed1992

Laminin immunohistochemistry in brain is dependent on method of tissue fixation.

Normal adult and lesioned rat and mouse brains were fixed by formaldehyde perfusion by two methods that differ primarily in the length of the post-fixation period. Sections were subsequently immunostained using monoclonal and polyclonal antibodies to laminin. With relatively short post-fixation periods (up to 4 h), vascular basement membrane (BM)-laminin was immunostained, but intraneuronal laminin-like immunoreactivity was faint. With longer post-fixation periods (18-24 h), intraneuronal laminin-like immunoreactivity was distinct, while vascular BM-laminin immunoreactivity was reduced drastically. These findings are particularly relevant to studies examining laminin immunoreactive blood vessels in response to lesions, especially ischemic stroke. In fact, the present results suggest that the apparent neovascularization or up-regulation of vascular BM-laminin following CNS injury likely relates to differences in regional tissue fixation.

Animals↗
PubMed1991

Identification of a 110-kDa nonintegrin cell surface laminin-binding protein which recognizes an A chain neurite-promoting peptide.

Laminin is a potent promoter of neurite outgrowth, and a synthetic peptide of 19 amino acids, PA22-2, from the A chain has been found to promote process formation. Using peptide affinity chromatography, we have identified a 110-kDa, cell surface ligand from both neural cells and brain which binds this sequence. This binding protein does not share immunological identity with the B1 chain of integrin, and reduction does not alter its mobility in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antibody to the 110-kDa protein stained cellular processes in vivo. Sequence analysis of the first 18 amino acids from the amino terminus yielded almost exact sequence identity with nucleolin, a major 110-kDa nucleolar phosphoprotein. Antibody to nucleolin, however, does not interact with the neural-derived, laminin-peptide-binding 110-kDa protein. The 110-kDa protein appears to be a ligand for a specific site on laminin.

Amino Acid Sequence↗
PubMed1991

Distinct immunoreactivity to 110 kDa laminin-binding protein in adult and lesioned rat forebrain.

A phosphorylated, approximately 110 kDa laminin-binding protein (110 kDa LBP) from mouse brain has been previously identified. This protein recognizes a neurite-outgrowth promoting 19-amino acid synthetic peptide (PA 22-2) derived from the laminin A chain. In the present study, an antibody against the 110 kDa LBP was used to localize immunoreactivity in the normal adult rat brain and also following a stab wound and ischemic lesion. Immunoreactive cells were found in layers II/III and V of the cerebral cortex and within apical dendrites of pyramidal neurons. Specific immunoreactivity was also found in the stratum lucidum in the CA3 region of the hippocampus which exhibited densely stained mossy fibers and terminals. Mechanical and ischemic lesions induced intense immunolabeling of reactive glial cells around the lesion site. The distinct and anatomically restricted localization of the immunostain in adult and lesioned rat brain suggests that 110 kDa LBP-like molecules might have an important function in forebrain structures and may be involved in the response to CNS injury.

Animals↗
PubMed1991

Fetal rat septal cells adhere to and extend processes on basement membrane, laminin, and a synthetic peptide from the laminin A chain sequence.

Responses of rat embryonic septal cells to reconstituted basement membrane, laminin, and laminin A chain-derived synthetic peptides were studied in culture. Dissociated fetal E16/17 septal cells were grown for three days on differently coated plastic substrata. Reconstituted basement membrane (Matrigel), laminin, and a 19-amino acid synthetic peptide CSRARKQAASIKVAVSADR-NH2 (PA22-2) from the laminin A chain sequence mediated cell-substratum adhesion and promoted neurite outgrowth. In contrast, cells did not attach to or form processes on uncoated plastic or on plastic substrata coated with synthetic, laminin-derived control peptides. Polyethylenimine (PEI) supported the adhesion and survival of fetal septal cells; however, when laminin was added to the medium during cell plating or 18 hr afterward, a dose-dependent increase was observed in neurite outgrowth of cells attached to this substratum. Cells grown for 6 days on PEI in the presence of laminin showed a determined increase in the number of cholinergic neurons as marked by acetylcholinesterase staining. These data suggest that the subpopulation of cholinergic septal neurons present in the septal cells studied here were also responding to laminin. The results of this in vitro study suggest potential uses for basement membrane, laminin, or synthetic peptides, such as PA22-2, in fetal septal grafts to enhance regeneration in the damaged septo-hippocampal system.

Acetylcholinesterase↗
PubMed1990

Parietal cortex lesions do not impair retention performance of rats in a 14-unit T-maze unless hippocampal damage is present.

Young male F-344 rats, pretrained in a straight runway to avoid shock, were then trained in a shock-motivated 14-unit T-maze. One day after maze acquisition, extensive parietal cortex lesions (PC) or sham operations (CON) were performed to assess possible involvement of parietal cortex in the age-related impairment previously observed in this task. Twelve days after surgery, a first 10-trial retention session in the 14-unit T-maze was conducted. One day later the vibrissae of half the rats in each group were clipped to examine involvement of the damaged barrel cortex field in maze performance of rats with PC lesions. The following day a second 10-trial retention session occurred. Finally, retention of the straight runway avoidance response was tested. Histological verification revealed a group with consistent parietal damage but also a subgroup with relatively small lesions to dorsal or lateral hippocampus in addition to parietal damage (PC + HIP). Behavioral results revealed virtually perfect maze retention for CON and PC rats. In contrast, PC + HIP rats were severely impaired in maze retention performance. Retention of the straight runway avoidance response was perfect in CON and PC rats but was impaired in PC + HIP rats. Vibrissae clipping did not affect error performance in the maze but led to a transitory increase in runtime. Overall, the results indicate that parietal lobe damage shortly after acquisition does not impair retention performance of young rats in the 14-unit T-maze, unless hippocampal damage is also evident. Thus, parietal lobe dysfunction alone would not appear to be involved in the age-related retention impairment previously observed in this task.

Aging↗
PubMed1989

Effects of brovincamine on stereological capillary parameters in adult and old Fischer-344 rats.

The intercapillary distance in the parietal cortex (area 39) and hippocampus (CA1 region) was greater in senescent Fischer-344 rats (27 1/2 months old) than in adult Fischer-344 rats (18 months old). Furthermore, an improvement was found in stereological parameter after a 42-day period of treatment with brovincamine (Sabromin) at dosages of 2.5, 5.0, and 10.0 mg/kg. Treated senescent rats showed a dose-dependent decrease in intercapillary distance and an increase in the number of capillary segments per measurement field compared with untreated controls. The values approximated those found in the adult control animals. In the adult rats the administration of the drug induced similar but far less marked changes in the stereology of the capillary network. The findings suggest that brovincamine affects the interactions between nerve cells, astroglia, and capillary blood flow (changes of the intercapillary microenvironment). The results show that a 42-day treatment with brovincamine decreases pericapillary resistance, thus supporting capillary microcirculation.

Aging↗
PubMed1988

Age-related changes in working and reference memory performance and locomotor activity in the Wistar rat.

Wistar rats of three age groups were tested in an automated tunnel-maze system of variable geometry to investigate whether changes in spontaneous locomotor activity and in learning and memory develop differentially or in a correlated fashion as a function of age. Senescent (30 months) as well as mature-adult (17 months) rats showed an age-correlated decline of locomotor activity as compared to the mature-young (5 months) group. Both working-memory (measured as within-trial arm discrimination performance) and reference-memory (measured as avoidance of "blind alley" visits) were severely affected in the senescent group, whereas the middle-aged animals suffered only from a working-memory deficit. The findings provide evidence that locomotor deficits do not necessarily interfere in the assessment of age-related changes in cognitive performance. Furthermore the results support the hypothesis that working and reference memory have different underlying physiological correlates and that these neuronal systems are differentially affected by the aging process.

Aging↗
PubMedDate not supplied

Laminins in the adult and aged brain.

Only recently have we become aware of the diversity of laminins in adult brain. In vascular basement membranes, the expression of at least five laminin chains has been demonstrated, suggesting the presence of several laminin variants. Recent ultrastructural evidence for heterogeneity of laminin expression in vascular basement membranes is an exciting finding, and points to structural and functional diversity of the basement membranes around cerebral blood vessels. Neuronal laminin-like immunoreactivity in the adult brain is a consistent observation, but does not fit well in the current understanding of the physiology and biochemistry of the heterotrimeric laminins. Nevertheless, the unique localization of putative neuronal laminins warrants their further characterization. The structure and function of laminins produced by reactive astrocytes in the lesioned adult brain and that seen in the brains of Alzheimer disease (AD) patients are not yet resolved. The possibility that these laminins play an important role in the CNS response to injury and pathophysiology of AD is expected to be a fruitful investigation. The next decade should see very significant advances in the characterization of brain laminins and, hopefully, in the elucidation of functional correlates to the structural diversity of laminins in brain.

Adult↗
PubMedDate not supplied

Age-related fibrillar deposits in brains of C57BL/6 mice. A review of localization, staining characteristics, and strain specificity.

The present article reviews findings regarding the age-related occurrence of clusters of unusual granules in the brains of C57BL/6 (B6) mice and discusses the potential relevance of this phenomenon as a model of specific aspects of brain aging in humans. The granules occur predominantly in the hippocampus of B6 mice and represent aggregations of fibrillar material that are mostly associated with astrocytes. The deposits become evident at about 4 to 6 mo of age, and increase markedly in both number and size thereafter. Similar structures have been observed in adult senescence accelerated mice (SAM) and have been noted, although very rarely, in older mice from other strains. The deposits appear to manifest dominant genetic heritability. Heparan sulfate proteoglycan and laminin or related molecules have been identified as components of the granular material. Although the deposits do not represent senile plaques with beta-amyloid deposition, they might mimic the deposition of extracellular matrix molecules that is thought to be an early event in amyloidogenesis in the aged brain and in Alzheimer's disease.

Aging↗
PubMedDate not supplied

Effects of aging and vincamine derivatives on pericapillary microenvironment: stereological characterization of the cerebral capillary network.

Changes in the pericapillary microenvironment of adult (18-month-old) and senescent (27 1/2-month-old) Fischer-344 rats treated for 6 weeks with daily IP injections of brovincamine or apovincamine (0, 2.5, 5, 10 mg/kg) were correlated with spontaneous locomotor activity and [14C]-2-deoxyglucose uptake of the brain. The animals were tested for spontaneous locomotor activity in a tunnel maze. Twenty-four hr after behavioral testing and subsequently after a [14C]-2-deoxyglucose injection, brains were removed and capillaries stained with alkaline phosphatase reaction, being later measured with an optical-electronic image analysis technique. Results revealed an increase in intercapillary distance, as a sensitive parameter for capillary density, in the hippocampus (CA1) and in the parietal cortex (area 39) in association with aging. Capillary diameter in the parietal cortex was found to be increased age dependently. A similar age-related increase was also observed in the CA1 field but this age trend was not significant. Chronic treatment with the vincamines produced a dose-dependent reduction in intercapillary distance in senescent animals which approached the level of untreated adult control rats. Significant negative correlations were found between maze locomotion and intercapillary distance among senescent rats. Furthermore, intercapillary distance and local relative 2-deoxyglucose uptake tended to be negatively correlated in both age groups. These findings provide evidence for the working hypothesis that mean intercapillary distance can be considered as an indicator of neuronal activity in the pericapillary microenvironment.

Aging↗
PubMedDate not supplied

3D-Reconstruction of microglia and amyloid in APP23 transgenic mice: no evidence of intracellular amyloid.

Microglia cells are closely associated with compact amyloid plaques in Alzheimer's disease (AD) brains. Although activated microglia seem to play a central role in the pathogenesis of AD, mechanisms of microglial activation by beta-amyloid as well as the nature of interaction between amyloid and microglia remain poorly understood. We previously reported a close morphological association between activated microglia and congophilic amyloid plaques in the brains of APP23 transgenic mice at both the light and electron microscopic levels [25]. In the present study, we have further examined the structural relationship between microglia and amyloid deposits by using postembedding immunogold labeling, serial ultrathin sectioning, and 3-dimensional reconstruction. Although bundles of immunogold-labeled amyloid fibrils were completely engulfed by microglial cytoplasm on single sections, serial ultrathin sectioning and three-dimensional reconstruction revealed that these amyloid fibrils are connected to extracellular amyloid deposits. These data demonstrate that extracellular amyloid fibrils form a myriad of finger-like channels with the widely branched microglial cytoplasm. We conclude that in APP23 mice a role of microglia in amyloid phagocytosis and intracellular production of amyloid is unlikely.

Alzheimer Disease↗
PubMedDate not supplied

Progressive age-related impairment of cognitive behavior in APP23 transgenic mice.

Transgenic APP23 mice expressing human APP(751) with the K670N/M671L mutation, were compared at ages 3, 18 or 25 months to non-transgenic littermates in passive avoidance and in a small and large Morris maze. The task in the smaller pool habituated their flight response to the platform. Impairments in passive avoidance and small pool performance in APP23 mice were clearly age-related. In the larger Morris maze APP23 mice at all ages were impaired in latency and distance swum before finding the platform. Identical performance of 18-month APP23 and controls in a visible platform condition indicates that the Morris maze performance deficit was not due to sensory, motor or motivational alterations. At age 3 months both groups initially unexpectedly avoided the visible platform, suggesting that in young mice neophobia may contribute significantly to performance in cognitive tests. In conclusion, APP23 mice exhibit both early behavioral impairment in the large Morris maze as well as impairments in passive avoidance and small pool performance that are marked only in old age.

Aging↗
PubMedDate not supplied

Stereological analysis of astrocyte and microglia in aging mouse hippocampus.

Recent evidence suggests neuroglia-mediated inflammatory mechanisms may stimulate neurodegenerative processes in mammalian brain during aging. To test the hypothesis that the number of microglia and astrocytes increase in the hippocampus during normal aging, unbiased stereological techniques were used to estimate total cell number in hippocampal subregions (CA1, dentate gyrus and hilus) of male C57BL/6J mice of different ages: 4-5 months, 13-14 months and 27-28 months. Immunocytochemical visualization for microglia and astrocytes were via Mac-1 and GFAP antibody, respectively. Estimates of total microglia and astrocyte number were assessed using the optical fractionator. No statistically significant age differences were found in the numbers of microglia or astrocytes in the hippocampal regions sampled. These findings suggest that age-related increases in the total numbers of hippocampal microglia and astrocytes is not causal for observed age-related increases in cytokine response.

Aging↗
PubMedDate not supplied

Hippocampal neuron and synaptophysin-positive bouton number in aging C57BL/6 mice.

A loss of hippocampal neurons and synapses had been considered a hallmark of normal aging and, furthermore, to be a substrate of age-related learning and memory deficits. Recent stereological studies in humans have shown that only a relatively minor neuron loss occurs with aging and that this loss is restricted to specific brain regions, including hippocampal subregions. Here, we investigate these age-related changes in C57BL/6J mice, one of the most commonly used laboratory mouse strains. Twenty-five mice (groups at 2, 14, and 28-31 months of age) were assessed for Morris water-maze performance, and modern stereological techniques were used to estimate total neuron and synaptophysin-positive bouton number in hippocampal subregions at the light microscopic level. Results revealed that performance in the water maze was largely maintained with aging. No age-related decline was observed in number of dentate gyrus granule cells or CA1 pyramidal cells. In addition, no age-related change in number of synaptophysin-positive boutons was observed in the molecular layer of the dentate gyrus or CA1 region of hippocampus. We observed a significant correlation between dentate gyrus synaptophysin-positive bouton number and water-maze performance. These results demonstrate that C57BL/6J mice do not exhibit major age-related deficits in spatial learning or hippocampal structure, providing a baseline for further study of mouse brain aging.

Aging↗
PubMedDate not supplied

Age-related psychomotor and spatial learning deficits in 129/SvJ mice.

The 129 mouse strain has been widely used to construct mutations that model behavioral aging in humans. The current study found significant age-related declines in both psychomotor and swim maze performance of 5-, 17-, and 27-month-old 129/SvJ mice. However, the age differences in swim maze acquisition were inconsistent with poor performance in the probe trial which assesses spatial memory. This inconsistency may result from the high degree of genetic polymorphisms and age-related visual pathology which afflicts this mouse strain. Therefore, we concluded that 129/SvJ mice present a problematic model of mammalian cognitive aging and involve a risk for behavioral contamination in studies involving mutant mice derived from this strain.

Aging↗