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P A Walicke

Publications and source records attributed to P A Walicke.

16 recordsLinked to original sources
PubMed1991

Localization of basic fibroblast growth factor and its mRNA after CNS injury.

Basic fibroblast growth factor (FGF) mRNA is increased 4 h after cortical brain injury. In situ hybridization reveals that the increased mRNA persists for at least 2 weeks and that, in areas adjacent and ipsilateral to the lesion, the expression of basic FGF mRNA is also modified. As an example, at three days distal from the lesion, mRNA can be detected in ependymal cells of the lateral ventricle and in selected cells of the hippocampus and cortex. Endothelial cells also synthesize basic FGF mRNA. The increase in basic FGF mRNA is paralleled by similar changes in the localization of the basic FGF protein. Both the intensity and number of cells which stain for basic FGF are increased when they are compared to staining in either the contralateral side or to comparable areas of unlesioned brains. The pattern of mRNA expression is similar from 4 hours to 14 days. Early in the response (4 h to 3 days) on the border of the lesion, the presence of basic FGF is most obvious within the MAC-1-immunopositive population (macrophages and/or microglia). From 7 days to 2 weeks, there has been extensive hypertrophy of the reactive astrocytes which stain intensely for anti-basic FGF(1-24). We conclude that there is increased basic FGF as a function of injury to the CNS. In view of the observation that it is an early and persistent response, the possibility that it plays multiple functions in the regenerative capacity of the CNS is discussed.

Animals↗
PubMed1991

Internalization and processing of basic fibroblast growth factor by neurons and astrocytes.

The fate of iodinated basic fibroblast growth factor (FGF) after its binding to cultured astrocytes and hippocampal neurons was studied. Autoradiography after light and electron microscopy establishes that, if cells are returned to 37 degrees C, the 125I-basic FGF bound internalizes into vesicles in the cytoplasm, localizes to the perinuclear cytoplasm, and is translocated to chromatin structures of the nucleus. The radiolabeled protein is long-lived, a finding confirmed by biochemical analyses. Polyacrylamide gel electrophoresis and autoradiography of both hippocampal neurons and astrocyte extracts reveal that these cells internalize 125I-basic FGF and then metabolize it to three major heparin-binding peptides with molecular weights of 15.5, 9, and 4 kDa. These peptides are initially detected 16 hr after binding to neurons and 4 hr after binding to astrocytes but are still detectable 48 and 16 hr, respectively, after initial binding (though present at lower levels). Immunoprecipitation with sequence-specific antisera to basic FGF reveals that the 15.5-kDa fragment is generated by cleavage at the carboxyl terminus, that the 9-kDa peptide contains the sequences between residues 30 and 87, and the 4-kDa peptide is a C-terminus fragment containing the sequence of basic FGF(106-120) but without basic FGF(139-146) immunoreactivity. The internalization of basic FGF is required for this processing; the treatment of cells with trypsin and 2 M NaCl at different times after binding can only prevent the metabolism of basic FGF if it is performed immediately after binding. Similarly, WGA, which inhibits basic FGF binding to its high-affinity receptor, prevents the metabolism of basic FGF. The possible significance of a metabolic pathway that is responsible for the processing of basic FGF after its internalization by cells in the CNS is discussed in light of its potential function as a neurotrophic factor.

Animals↗
PubMed1989

Characterization of the neuronal receptor for basic fibroblast growth factor and comparison to receptors on mesenchymal cells.

The receptor for basic fibroblast growth factor (bFGF) was characterized in highly enriched cultures of fetal hippocampal neurons. Two major components of binding could be distinguished. One component comprising about 70% of total binding was removed by 2 M NaCl, and by analogy to other cells could be presumptively attributed to glycosaminoglycans. The remaining 30% of binding which was resistant to 2 M NaCl reflects a high affinity receptor. Scatchard analysis indicated that the two components have Kd values of 500 and 120 pM, and densities of 165,000 and 35,000-60,000 sites/neuron, respectively. Cross-linking 125I-bFGF to neuronal cultures with disuccinimidyl suberate labeled a major membrane protein of 135 kDa and a minor protein of 85 kDa. Examination of neuronal cultures derived from multiple brain regions and membrane preparations from fetal brain suggested that the larger protein was widely distributed. The neuronal bFGF receptor was not blocked by heparin at concentrations up to 100 micrograms/ml. Twelve synthetic peptide fragments of bFGF were examined to determine the domain of bFGF interacting with the neuronal receptor. Inhibition was observed chiefly with a peptide including the sequence 103-146. The properties of the neuronal bFGF receptor were compared directly to those of the receptors characterized on BHK cells and other mesenchymal cells. Specific differences observed between neuronal and mesenchymal bFGF receptors are discussed.

Animals↗
PubMed1989

Fibroblast growth factors.

The existence of fibroblast growth factors (FGFs) was proposed over 40 years ago to account for the ability of tissue extracts to stimulate fibroblast proliferation. In the 1970s it became clear that preparations containing FGF activity were in fact pleiotropic, affecting the growth and function of a wide variety of mesenchymal, endocrine and neural cells. Their angiogenic effects have promoted research in cardiology and neurology because of their proposed role in stimulating collateral vascularisation and recovery from ischemia. Their identity with a component of tumour angiogenesis factor activity has stimulated research in oncology and their capacity to enhance wound healing, nerve regeneration and cartilage repair has affected research in neurology, orthopaedic medicine and pathology. The potential therapeutic value of FGFs is just beginning to be realized and will be dependent on a concerted effort to establish their function in the regulation of normal cell homeostasis and the pathophysiology of disease.

Animals↗
PubMed1989

Basic fibroblast growth factor (FGF) in the central nervous system: identification of specific loci of basic FGF expression in the rat brain.

The expression of basic FGF mRNA, while virtually absent in peripheral tissues, appears to be constitutively expressed in the central nervous system. As such, while it is difficult to detect any mRNA encoding basic FGF in the heart, lung, kidneys, ovaries, liver, or pituitary of rats, the levels are easily detected in brain. A regional analysis of the expression of basic FGF mRNA in brain reveals that it is widely distributed in the cortex (frontal, parietal, and occipital), the hippocampus, hypothalamus, and pons. Only a few loci of basic FGF synthesis are detected by in situ hybridization and include layers 2 and 6 of the medial (cingulate) cortex, the indusium griseum, fasciola cinereum, and field CA2 of the hippocampus. The identification of specific cell populations in the brain, and particularly in the hippocampus, that synthesize basic FGF supports the notion that this potent neurotrophic factor is involved in normal CNS function and that the presence (or absence) of its expression may be linked to the pathogenesis of the neurogenerative diseases characterizing these various loci. The significance of these findings with respect to the regulation of basic FGF expression in peripheral tissue and the central nervous system is discussed.

Animals↗
PubMed1989

Neuropsychological evidence for multiple implicit memory systems: a comparison of Alzheimer's, Huntington's, and Parkinson's disease patients.

The performances of patients with dementia of the Alzheimer type (DAT), patients with Huntington's disease (HD), and demented and nondemented patients with Parkinson's disease (PD) were compared on 2 tests of implicit memory that do not require the conscious recollection of prior study episodes: (1) a pursuit-rotor motor learning task and (2) a lexical priming test. The HD patients were found to be impaired on the motor learning but not the lexical priming task, whereas the DAT patients evidenced the opposite relationship on these tasks. The demented, but not the nondemented, PD patients were found to be impaired on both tests of implicit memory. For both the HD and PD patients, deficits on the motor learning task correlated significantly with severity of dementia but not with level of primary motor dysfunction. The noted double dissociation between HD and DAT patients indicates that different forms of implicit memory, all of which are intact in amnesia, are dependent upon distinct neuroanatomic systems. Motor skill learning may be mediated by a corticostriatal system, whereas verbal priming may depend upon the integrity of the neocortical association areas involved in the storage of semantic knowledge. The results for the PD patients suggest that the demented PD patients have endured damage to the neurologic systems subserving both motor learning and lexical priming.

Alzheimer Disease↗
PubMed1988

Neurotrophic effects of basic and acidic fibroblast growth factors are not mediated through glial cells.

Basic and acidic fibroblast growth factors (bFGF, aFGF) increase the survival of fetal hippocampal pyramidal neurons in serum-free cultures. bFGF is also a mitogen for astrocytes either in highly purified glial cultures or as a contaminant in neuronal cultures. The possibility that bFGF enhances neuronal survival indirectly through stimulating glial proliferation is unlikely. In the presence of 1 ng/ml bFGF, the total number of contaminating astrocytes (as defined by immunohistochemical staining for glial fibrillary acidic protein (GFAP] was increased to 4.3% vs 0.9% in control hippocampal cultures. aFGF did not significantly increase astrocyte number while supporting neuronal survival. Two other agents which stimulated equal or greater astrocytic proliferation, epidermal growth factor (EGF) and 10% serum, did not support neurons, and bFGF still significantly increased neuronal survival in their presence. When glial proliferation was inhibited by aphidicolin, contamination decreased to 0.1% in controls and 1.0% with 1 ng/ml bFGF, yet the neurons remained responsive to FGF. Cultures lacking any detectable GFAP-positive cells were identified, and even in the absence of glial cells, aFGF and bFGF increased neuronal survival. Because there is no significant correlation between the neuronal response and astrocyte number, it appears that bFGF and aFGF can directly support neuronal survival.

Animals↗
PubMed1988

Interactions between basic fibroblast growth factor (FGF) and glycosoaminoglycans in promoting neurite outgrowth.

Basic fibroblast growth factor (bFGF) is a heparin-binding protein which has trophic effects on hippocampal neurons in vitro. It stimulates neurite extension when bound to surfaces coated with heparin, heparan sulfate, or hyaluronic acid, but not chondroitin sulfate or dermatan sulfate. Stimulation of neurite growth correlated strongly with the amount of [125I]bFGF bound by the different glycosoaminoglycans. Providing accessible stores of bFGF might be one function of glycosoaminoglycans during development.

Animals↗
PubMed1988

Basic and acidic fibroblast growth factors have trophic effects on neurons from multiple CNS regions.

Basic fibroblast growth factor (bFGF) supports the survival of neurons from many regions of the E18 fetal rat brain. Survival was significantly increased for neurons derived from the hippocampus, entorhinal cortex (EC), frontal cortex, parietal cortex (PC), occipital cortex, striatum, septum, and thalamus, but not from the subiculum (Sb). The proportion of neurons rescued by bFGF varied among brain regions, suggesting the existence of subpopulations of responsive neurons. Like hippocampal neurons, neurons from the EC and PC required about 1 pM bFGF (10-20 pg/ml) for half-maximal response; striatal neurons, in contrast, required about 3 pM bFGF. Neurite outgrowth after 24 hr exposure was significantly increased for neurons from the hippocampus, EC, and PC, while striatal neurons had only a marginal response. Although bFGF stimulated some astrocytic proliferation in the cultures, glial contamination was maintained at 2% or less. Acidic FGF (aFGF) supported smaller numbers of neurons from each region, although it significantly increased survival of neurons from hippocampus, EC, PC, striatum, and Sb. The concentration required for half-maximal survival was around 100-300 pM (2-5 ng/ml). It appears that bFGF and aFGF are potent trophic factors for many populations of CNS neurons and could potentially play a significant role in nervous system development.

Animals↗
PubMed1986

Neurogenic bladder from occult herpes zoster.

Active infection with herpes zoster may cause acute urinary retention, especially when it involves sacral dermatomes. Although frank retention usually develops days to weeks after eruption of the typical rash, bladder incompetence infrequently develops first, raising concern over other, more ominous etiologies. In the case presented, rash appearance was delayed until six weeks after the initial onset of urinary retention, a much longer interval than previously reported. Occult herpes zoster infection should be considered in patients presenting with an acute neurogenic bladder of obscure cause.

Acyclovir↗
PubMed1981

On the role of cyclic nucleotides in the transmitter choice made by cultured sympathetic neurons.

Previous investigations have established that electrical activity or chronic depolarization influences the development of neonatal rat sympathetic neurons in dissociated cell culture. Depolarization reduces their ability to respond to a cholinergic inducing factor produced by non-neuronal cells, allowing normal adrenergic differentiation to proceed (Walicke, P., R. Campenot, and P. Patterson (1977) Proc. Natl. Acad. Sci. U. S. A. 74: 5767-5771). The present study examines whether the developmental effects of depolarization are mediated through cyclic nucleotides. Addition of dibutyryl cAMP, dibutyryl cGMP, adenosine, prostaglandin E1, and cholera toxin all raise neuronal cyclic nucleotide levels and qualitatively mimic the developmental effects of depolarization. However, the quantitative decrease in acetylcholine production caused by these cyclic nucleotide agents is much smaller than that caused by depolarization. Short (48-hr) exposures to the cyclic nucleotide derivatives do not alter transmitter synthesis, indicating that long term developmental changes are involved. Chronic depolarization with elevated K+ increases neuronal cAMP 2-fold but has little effect on cGMP. The increase in cAMP is maintained during several weeks of depolarization and is present as early as the 3rd day in vitro, preceding the significant alterations in adrenergic and cholinergic differentiation. Exposure to 2 mM theophylline also increases neuronal cAMP, but in contrast to the other agents, it enhances cholinergic differentiation. In combination with elevated K+, theophylline further increases neuronal cAMP but still favors cholinergic differentiation. Thus, although cAMP satisfies some criteria for being the second messenger in the developmental effects of depolarization, several findings are consistent with the nucleotide playing a central role: (i) Depolarization has much larger effects on transmitter choice than the cyclic nucleotide agents and (ii) theophylline can uncouple cyclic nucleotide levels from the developmental events.

Acetylcholine↗
PubMed1977

Determination of transmitter function by neuronal activity.

The role of neuronal activity in the determination of transmitter function was studied in cultures of dissociated sympathetic neurons from newborn rat superior cervical ganglia. Cholinergic and adrenergic differentiation were assayed by incubating the cultures with radioactive choline and tyrosine and determining the rate of synthesis and accumulation of labelled acetylcholine and catecholamines. As in previous studies, pure neuronal cultures grown in control medium displayed much lower ratios of acetylcholine synthesis to catecholamine synthesis than did sister cultures grown in medium previously conditioned by incubation on appropriate nonneuronal cells (conditioned medium). However, here we report that neurons treated with the depolarizing agents elevated K(+) or veratridine, or stimulated directly with electrical current, either before or during application of conditioned medium, displayed up to 300-fold lower acetylcholine/catecholamine ratios than they would have without depolarization, and thus remained primarily adrenergic. Elevated K(+) and veratridine produced this effect on cholinergic differentiation without significantly altering neuronal survival. Because depolarization causes Ca(2+) entry in a number of cell types, the effects of several Ca(2+) agonists and antagonists were investigated. In the presence of the Ca(2+) antagonists D600 or Mg(2+), K(+) did not prevent the induction of cholinergic properties by conditioned medium. Thus depolarization, either steady or accompanying activity, is one of the factors determining whether cultured sympathetic neurons become adrenergic or cholinergic, and this effect may be mediated by Ca(2+).

Acetylcholine↗
PubMedDate not supplied

How well do we understand neurotrophic factors and the control of CNS neuronal growth?

The review of Hefti et al. (7) presents current theories and concepts about the functions and activities of neurotrophic factors (NTF). The validity of several components and assumptions may be questionable. Should NTFs be divided into small diffusible survival-promoting factors and large, insoluble neurite-promoting factors? How are NTFs and neurotransmitters related? Do neurons need one or several NTFs? Can NTFs be multifunctional trophic factors? Are there endogenous inhibitory modulators of neuronal growth? Answers to these questions may have significant impact on the design of therapies using NTFs.

Animals↗