Christopher Frederickson - Academia.edu (original) (raw)

Papers by Christopher Frederickson

Encyclopedia of Metalloproteins, 2013

The present invention provides methods of determining if an individual is at risk for prostate ca... more The present invention provides methods of determining if an individual is at risk for prostate cancer. The methods measures and compares free and/or bound zinc levels in a semen sample or prostatic fluid, including post massage expressed prostatic fluid, in the potential at risk individual with normal levels. A decrease in zinc level is indicative of a risk for prostate cancer.

Journal of Alzheimer's disease : JAD, 2005

Prior brain injury is a major risk factor in the development of Alzheimer's disease. This is ... more Prior brain injury is a major risk factor in the development of Alzheimer's disease. This is true for traumatic brain injury, stroke or ischemic brain injury, and (more speculatively) for brain injury resulting from the hypo-perfusion-reperfusion in cardiac arrest or cardiac bypass surgery and even hypo- or hypertension. Here we propose that the release of excess, toxic, "floods" of free zinc into the brain that occurs during and after all excitotoxic brain injury is a key factor that sets the stage for the later development of Alzheimer's disease. Rapid and aggressive administration of zinc buffering compounds to patients suffering brain injury may therefore not only ameliorate the acute injury but might also reduce the risk of subsequent development of Alzheimer's disease.

Behavioral and neural biology, 1980

Hippocampal rhythmical slow activity (RSA) was recorded from four chronically implanted cats duri... more Hippocampal rhythmical slow activity (RSA) was recorded from four chronically implanted cats during the preresponse interval of both a cued and a noncued delayed response task. Significantly more RSA was recorded during the cued than the noncued delay interval, even though the animals sat essentially immobile throughout the entire delay interval in both the cued and the noncued conditions. The results suggest that the occurrence of immobility-related RSA can be directly influenced by manipulation of a relevant sensory cue.

Neuroscience, 1990

Intraperitoneal injections of sodium selenite result in the formation of zinc-selenium complexes ... more Intraperitoneal injections of sodium selenite result in the formation of zinc-selenium complexes in zinc-containing axonal boutons ("Timm stainable boutons"), and the zinc-selenium precipitate can be rendered visible in histological sections by silver enhancement. In this work we present evidence, in the rat, that zinc-selenium precipitates formed in vivo after intraperitoneal injections of sodium selenite are translocated by colchicine-sensitive retrograde transport to neural perikarya when animals are allowed to survive 12-24 h after the selenite administration. Silver enhancement renders the perikaryal precipitates visible and thus demonstrates the perikarya of all zinc-containing neurons in the CNS simultaneously. Large populations of zinc-containing neurons identified by the method are found in layers II, III, and VI of all neocortical areas, in the superficial and deep layers of the prepyriform areas and, with a high degree of regional differentiation, in the retrosp...

AbstractöOne of us showed previously [Cuajungco and Lees (1998) Brain Res. 799, 188^129] that nit... more AbstractöOne of us showed previously [Cuajungco and Lees (1998) Brain Res. 799, 188^129] that nitric oxide injected into the cerebrum in vivo causes zinc staining to appear in the somata of neurons and suggested that this staining of somata might be accompanied by a depletion (release) of zinc from axon terminals. In the present study, we con¢rm earlier results and report that there is a dramatic loss (apparent release) of histologically reactive zinc from the boutons of zinc-containing axons induced by infusion of nitric oxide into the brain in vivo. Rats were anesthetized with halothane and a cannula was inserted into the hippocampus. Either nitric oxide donor (spermineNONOate, 100 mM/2 Wl) or control (spermine, 100 mM/2 l) was infused into the hippocampus or the cerebellar cortex. Two hours after infusion, N-(6methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) staining for zinc in the brains revealed that sperminenitric oxide, but not control (spermine only) produced up to 95% depletion of zinc staining from the zinc-containing boutons. TSQpositive neurons were also conspicuous throughout injection sites, in both the cerebral cortex and in the cerebellar cortex, where the Purkinje neurons were especially vivid, despite the scarcity of zinc-containing axonal boutons. It is suggested that the TSQ-stainable zinc in somata might represent intracellular stores mobilized from within or permeating extracellular stores. ß

Science Signaling, 2003

It is now completely clear that at least a dozen types of mammalian cells sequester rather startl... more It is now completely clear that at least a dozen types of mammalian cells sequester rather startling amounts of "free" zinc in their secretory granules and secrete that zinc in regulated fashion, under the precise control of action potentials (in neurons) and secretagogues (in non-neural cells 1,2 ). Furthermore, it is becoming more and more clear that the secreted zinc is not just some epiphenomenon that accompanies secretion of the "real" messengers from these cells. Indeed, to paraphrase McLuhan, it appears that "the cationic medium is the message." Specifically, the brief "puffs" of ionic (rapidly-exchangeable) Zn 2+ that cells deliver into their immediate microenvironment are now recognized as pivotal and essential modulators and mediators of cell-to-cell signaling . Even more intriguing, cases are emerging in which the Zn 2+ released by one cell travels through specific, gated, zinc-permeable channels in adjacent cells to enter the latter. This makes the Zn 2+ ion an orthograde, transcellular, transmembrane signal, a completely novel signal type 5,6 .

Physiology & Behavior, 1977

FREDERICKSON, C. J. AND I. Q. WHISHAW. Hippocampal EEG during learned and unlearned behavior in t... more FREDERICKSON, C. J. AND I. Q. WHISHAW. Hippocampal EEG during learned and unlearned behavior in the rat. PHYSIOL. BEHAV. 18(4) 597-603, 1977. -EEG was recorded from the dorsal hippocampus of 10 rats trained to bar press or to lick or chew manipulanda for food reinforcement. Even after prolonged practice, and regardless of the behavior employed, all animals showed essentially continuous rhythmical slow activity (RSA) during bar pressing. RSA was larger in amplitude and lower in frequency during high-rate (FR 50) than intermittent (CRF) bar pressing and likewise tended to be larger amplitude and lower frequency during high-rate pressing (FR 72) after 6 weeks practice than during lower-rate pressing (FR 72) after only 4 weeks practice. When emitted as operants licking and chewing were accompanied by large amplitude irregular activity (LIA). The results suggest that learned motor behavior in the rat is accompanied by RSA no matter how thoroughly practiced it may be, that frequency and amplitude of RSA are closely related to the motor pattern of ongoing motor behavior, and that behaviors such as licking and chewing are accompanied by LIA regardless of the circumstances in which they occur.

NeuroReport, 1994

Zinc-containing neurons are cells that sequester zinc presynaptically and release it when active.... more Zinc-containing neurons are cells that sequester zinc presynaptically and release it when active. Previously such neurons have been found almost exclusively in cerebrocortical and amygdalar regions. Here we describe a thalamo-cortical pathway that is zinc-containing, namely, the projection from the anterodorsal nucleus of the thalamus to the subicular cortex. The pathway was identified by the zinc-specific retrograde transport methods; its addition to the zinc-containing cerebral circuitry reinforces the association of the zinc-containing terminals with cortico-limbic systems.

Neurochemistry International, 1995

Almtraet--The subiculum is densely innervated by zinc-containing axonal terminals, but the cells ... more Almtraet--The subiculum is densely innervated by zinc-containing axonal terminals, but the cells of origin of those zinc-containing afferents have not previously been identified. In the present work the zinc-specific retrograde tracing method was employed to locate the zinc-containing neurons afferent to the subicular complex. Following microinfusions into the subicular region, the somata of zinc-containing neurons were found in the hippocampus, the pre-and para subiculum, retrosplenial, cingulate, and perirhinal cortices, and in the anterodorsal nucleus of the thalamus. The results show another component of the zinc-containing associational network that interconnects the cerebral cortex and amygdalohippocampal systems of the brain.

Journal of Histochemistry & Cytochemistry, 1992

Journal of Histochemistry & Cytochemistry, 2006

S U M M A R Y We have used a new family of zinc-specific-responsive fluorescent dyes (ZPs) to stu... more S U M M A R Y We have used a new family of zinc-specific-responsive fluorescent dyes (ZPs) to study the sequestration and secretion of zinc from Paneth cells, which are located in the bases of the crypts of Lieberkü hn within the rat small intestine. Vivid ZP fluorescence zinc staining of Paneth cell secretory granules is seen in both cryostat sections and isolated crypts, providing firm evidence for a pool of labile (rapidly exchangeable) zinc within these cells. We further demonstrate that this ionic zinc pool is secreted under physiological conditions. In vivo stimulation of the small intestine by IP injection of the secretagogue pilocarpine results in discrete zinc staining within the lumens of subsequently isolated crypts, concomitant with a decrease in the zinc staining of Paneth cell granules located within the same crypts. In contrast, the secretion of zinc into the lumens of isolated crypts stimulated in vitro with either carbachol or LPS (lipopolysaccharide) is not observed. However, a distinct change in Paneth cell morphology, suggesting attempted secretion, is seen in response to the direct application of cholinergics but not LPS. These findings suggest that zinc is coreleased with other Paneth cell anti-microbials, and that the intact intestine is necessary for secretion into the crypt lumen. (J Histochem Cytochem 54:311-316, 2006)

The Journal of Comparative Neurology, 1998

The mammalian amygdaloid complex is densely innervated by zinc-containing neurons. The distributi... more The mammalian amygdaloid complex is densely innervated by zinc-containing neurons. The distribution of the terminals throughout the region has been described, but the origins of these zinc-containing fibers have not. The present work describes the origins of one major component of the zinc-containing innervation of the amygdaloid complex, namely, the component that innervates the corticomedial complex. Selective labeling of zinc-containing axons was accomplished by intracerebral microinfusion of selenium anions (SeO3(2-)), a procedure that produces a ZnSe precipitate in zinc-containing axonal boutons with subsequent retrograde transport to the neurons of origin. After infusions of SeO3(2-) into combinations of cortical, medial, or amygdalohippocampal regions, retrogradely labeled zinc-containing somata were found in all amygdaloid nuclei except for the medial and central nuclei, the bed nucleus of the accessory olfactory tract, the nucleus of the lateral olfactory tract, and the anterior amygdaloid area. Extrinsic zinc-containing projections to the same amygdaloid terminal fields were found to originate from the infralimbic, cingulate, piriform, perirhinal and entorhinal cortices, and from the prosubiculum and CA1. Commissural zinc-containing projections were found to originate from the posterolateral and posteromedial cortical nuclei and from the posterior part of the basomedial nucleus. Zinc-containing neurons have been implicated in the pathophysiology of epilepsy, in cell death after seizure or stroke, and in Alzheimer's disease, all clinical conditions that involve the amygdaloid complex. Identification of the zinc-containing pathways is a prerequisite to the elucidation of zinc's role in these disorders.

The Journal of Comparative Neurology, 1989

Many regions of the basal forebrain are innervated by zinc-containing axonal boutons. In the pres... more Many regions of the basal forebrain are innervated by zinc-containing axonal boutons. In the present work, the lesioddegeneration method, coupled with histochemical staining for zinc-containing boutons, was used to determine the origins and efferent pathways of these zinc-containing projections to the basal forebrain.

Journal of Chemical Neuroanatomy, 1992

The nlajor cytoarchitectonic regions of the rat brain that stain with the Timm l)anscher metal sl... more The nlajor cytoarchitectonic regions of the rat brain that stain with the Timm l)anscher metal slain ~ere tested with the flourescent probe for zinc, 6-methoxy 8-para toluene sulfonamide quinoline (ISQ). Throughout most of the striatum, cerebral cortex and limbic system, tile diffuse, even neuropil staining produced by the Timm Danscher method was mirrored by comparable fluorescence in TSQ-stained sections. Blockade of the TSQ fluorescence by prior treatment with sulphide indicated that tile limm Danschcr and tile TSQ procedures both labeled the same pool of endogenous metal, which is in fcrrcd to bc tile zinc that is in axonal boutons. It is concluded that the Tilnm l)anscher staining generally indicates zinc-containing axonal boutons. Tile distribution of the zinc-containing axonal boutons throughout the forcbram is described.

Journal of Cerebral Blood Flow & Metabolism, 2006

Hypothermia reduces excitotoxic neuronal damage after seizures, cerebral ischemia and traumatic b... more Hypothermia reduces excitotoxic neuronal damage after seizures, cerebral ischemia and traumatic brain injury (TBI), while hyperthermia exacerbates damage from these insults. Presynaptic release of ionic zinc (Zn 2 þ ), translocation and accumulation of Zn 2 þ ions in postsynaptic neurons are important mechanisms of excitotoxic neuronal injury. We hypothesized that temperature-dependent modulation of excitotoxicity is mediated in part by temperature-dependent changes in the synaptic release and translocation of Zn 2 þ . In the present studies, we used autometallographic (AMG) and fluorescent imaging of N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) staining to quantify the influence of temperature on translocation of Zn 2 þ into hippocampal neurons in adult rats after weight drop-induced TBI. The central finding was that TBI-induced Zn 2 þ translocation is strongly influenced by brain temperature. Vesicular Zn 2 þ release was detected by AMG staining 1 h after TBI. At 301C, hippocampus showed almost no evidence of vesicular Zn 2 þ release from presynaptic terminals; at 36.51C, the hippocampus showed around 20% to 30% presynaptic vesicular Zn 2 þ release; and at 391C vesicular Zn 2 þ release was significantly greater (40% to 60%) than at 36.51C. At 6 h after TBI, intracellular Zn 2 þ accumulation was detected by the TSQ staining method, which showed that Zn 2 þ translocation also paralleled the vesicular Zn 2 þ release. Neuronal injury, assessed by counting eosinophilic neurons, also paralleled the translocation of Zn 2 þ , being minimal at 301C and maximal at 391C. We conclude that pathological Zn 2 þ translocation in brain after TBI is temperature-dependent and that hypothermic neuronal protection might be mediated in part by reduced Zn 2 þ translocation.