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J E Marchand

Publications and source records attributed to J E Marchand.

36 records · Page 2Linked to original sources
PubMed1991

Biochemical characterization and anatomical distribution of a major form of unamidated precursor of substance P in rat brain.

Previous work from this laboratory has provided biochemical characterization of several posttranslational processing intermediates of the neuropeptide substance P (SP) in central nervous system (CNS) tissues, including the COOH-terminal glycine-extended dodecapeptide Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-Gly (SP-G). SP-G is a major species of unprocessed SP found in rodent CNS tissues, and is the likely immediate precursor form of SP in the biosynthetic scheme. Here we present extensive characterization of the normal regional distribution of SP-G, as compared to SP, throughout the rat CNS via coordinated biochemical and morphological analyses. By radioimmunoassay (RIA), an approximate 10-fold variation in regional levels of SP-G-like immunoreactivity (SP-G-LI) was observed, ranging from 0.30 pmol/g in the amygdala, to 6.49 pmol/g in the medulla. On a normalized basis, the regional variation of unamidated precursor relative to mature peptide (SP-G-LI/SP-LI molar ratio) ranged from 0.30% in the amygdala to 5.15% in the dorsal root ganglia (DRG). Overall, the highest SP-G-LI/SP-LI ratios were found in DRG, medulla, and spinal cord, i.e. CNS areas associated with primary sensory afferent innervation via capsaicin-sensitive unmyelinated small diameter fibers. In addition, chromatographic and RIA analyses of extracted brain tissues indicated that the quantified immunoreactivities corresponding to SP, SP-G, as well as an additional COOH-terminal Gly-Lys-extended precursor, i.e., SP-G-K, displayed very similar chromatographic behavior as demonstrated for chemically authentic standards. These biochemical data were complemented by immunohistochemical analyses demonstrating a pattern of immunohistochemical staining for the presence of SP-G-LI as a defined subset of SP-LI-containing neural elements. Here, reaction product was localized to dendritic, axonal, and terminal neuronal elements in representative CNS regions of the rat, with relatively high levels of SP-G-LI found within anatomical areas containing a high density of sensory terminal structures. In an attempt to provide correlative functional anatomy, a group of rats was treated with colchicine, in order to differentially localize SP-LI- and SP-G-LI-containing somata after inhibition of axoplasmic transport. Most prominently, colchicine administration engendered immunohistochemical visualization of both SP-LI- and SP-G-LI-positive cells in mesencephalic and brainstem regions associated with stress, pain responses, and central control of autonomic function. Within this context, the coordinate expression of both SP-LI- and of SP-G-LI-positive somata in discrete brain areas is probably indicative of high ongoing rates of tachykinin synthesis coupled to utilization.

Amino Acid Sequence↗
PubMed1990

Disulfiram administration affects substance P-like immunoreactive and monoaminergic neural systems in rodent brain.

The biosynthetic enzyme peptidylglycine alpha-amidating monooxygenase catalyzes the formation of a variety of biologically active alpha-amidated peptides from respective COOH-terminal glycine-extended peptide precursors. Peptidylglycine alpha-amidating monooxygenase activity is dependent on copper, ascorbate, and molecular oxygen and is inhibited by the relatively selective copper chelator N,N-diethyldithiocarbamate or its disulfide dimer disulfiram (Antabuse). In the present study, chronic disulfiram treatment (100 mg/kg/day, for 12-25 days) resulted in significant changes in several neurochemical parameters in the mouse central nervous system, including levels of substance P-like, unamidated substance P-Gly-like, and protease-generated substance P-Gly-Lys-like immunoreactivities (SP-LI, SP-G-LI, and SP-G-K-LI, respectively). Combined high performance liquid chromatography/radioimmunoassay analyses of the extracted SP-LI, SP-G-LI, and SP-G-K-LI species indicated very similar chromatographic and immunochemical behavior as demonstrated for chemically authentic peptide standards. Additionally, changes in levels of monoamines and their metabolites were observed after drug administration. Complementary immunohistochemical analyses using affinity-purified anti-SP-G sera localized these drug-induced changes in levels of immunoreactive unamidated precursor to neural elements that normally express SP. As a functional corollary to alterations in neurochemical parameters, we observed significant disulfiram-induced increases in pain thresholds, potentiated by capsaicin treatment. Overall, our results indicate that the observed changes in steady state levels of immunoreactive SP and of the immature COOH-terminal extended forms of SP may reflect compensatory biosynthetic and posttranslational processing events in SP-containing neural systems after pharmacological challenge.

Amino Acid Sequence↗
PubMed1985

Topographic organization of tufted cell axonal projections in the hamster main olfactory bulb: an intrabulbar associational system.

The organization of intrinsic axonal projections of principal neurons in the main olfactory bulb (MOB) was studied in hamsters by using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and fluorescent dyes. Punctate injections of either WGA-HRP or fast blue (FB) that are restricted to small sectors on one side of the MOB produce comparably restricted fields of retrograde labeling on the opposite side. Label is found predominantly in superficially situated (middle and external) tufted cells that lie near and at the border between the external plexiform and glomerular layers. Few of the deeper middle tufted, internal tufted, or mitral cells and no external tufted cells that lie in the superficial two-thirds of the glomerular layer are labeled in regions remote to the injection site. Anterograde transport of WGA-HRP from the injection site labels axons that travel dorsally and ventrally in restricted bands through the internal plexiform layer and then terminate within this layer in the punctate sector on the opposite side that contains retrogradely labeled neurons. Such reciprocal projections between opposing regions of the medial and lateral sides of the MOB are found at all rostrocaudal and dorsoventral levels. When punctate injections of FB into the MOB are paired with restricted injections of a second fluorescent tracer (nuclear yellow or diamidino yellow dihydrochloride) into the appropriate sector of pars externa (pE) of the anterior olfactory nucleus, the punctate region of remote retrogradely labeled principal neurons is embedded within a topographically restricted longitudinal wedge of retrogradely labeled mitral and tufted cells that project extrinsically to or through pE. However, extremely few of these neurons are double-retrogradely labeled. The results reveal the existence of an intrabulbar associational system in which principal neurons engage in point-to-point, reciprocal projections between opposing regions of the medial and lateral MOB. Moreover, the results indicate that this associational system largely arises from superficially situated tufted cells distinct from those that support bulbofugal projections into the topographically organized interbulbar commissural system via pE.

Animals↗
PubMed1983

Evidence for a cyclic GMP mechanism in the mediation of hippocampal post-tetanic potentiation.

Correlative electrophysiological and biochemical techniques were used to study hippocampal post-tetanic potentiation in acutely prepared rabbits following stimulation of the medial septal region and contralateral hippocampal field CA3. The results indicate that calcium ions, guanosine-3':5'-monophosphate, and phosphodiesterase inhibitors selectively enhanced the duration of post-tetanic potentiation. Potassium ions selectively enhanced tetanic potentiation. Adenosine-3':5'-cyclic monophosphate suppressed both tetanic and post-tetanic potentiation. The electrophysiological findings were supported by biochemical observations that guanosine-3':5'-monophosphate levels show marked increases following tetanic stimulation of either the medial septal region or contralateral hippocampal field CA3 pathways. The data suggest that a calcium-dependent process in the presence of a guanosine-3':5'-monophosphate mechanism promotes periods of hippocampal pyramidal cell hyperexcitability. The mechanism by which the cyclic nucleotide alters potentiation does not appear to be coupled to a single receptor variety.

Animals↗
PubMed1983

Effects of iontophoretically applied norepinephrine and dopamine on fimbria-evoked activity in the lateral septum.

Norepinephrine (NE) and dopamine (DA) are present in the lateral septum and presumably modulate activity of neurons in this region. Iontophoretic techniques were used to study the actions of NE and DA on stimulation-evoked activity of neurons in the lateral septum. Stimuli were applied to the fimbria, and the effects of NE and DA on field and unitary responses were recorded. Norepinephrine strongly inhibited the monosynaptically driven negative field potential and associated unitary responses. Dopamine produced an inhibitory, excitatory, or bimodal pattern of changes in the monosynaptic responses. Ventrally in the lateral septum, where a later polysynaptic excitatory response to fimbria stimulation was also seen, NE and DA augmented the polysynaptic responses, while producing inhibitory (NE) or inhibitory-excitatory (DA) effects on the monosynaptic response. Effects of NE and DA may play a role in modulation of the relay of descending hippocampal input to the medial septum, which is relayed by way of neurons in the lateral septum. In this manner catecholamines may indirectly produce modulatory effects in the theta pace-making cells in the medial septum.

Animals↗
PubMed1983

Afferents to the periaqueductal gray in the rat. A horseradish peroxidase study.

Afferent projections to the periaqueductal gray matter in the rat have been studied by use of the retrograde axonal transport of horseradish peroxidase. Iontophoretic injections of horseradish peroxidase were made in dorsal, lateral and medial areas of the periaqueductal gray, primarily at intercollicular levels. The pattern of projections was similar in all of the injections restricted to the periaqueductal gray. Within the brainstem, numerous reticular formation nuclei were labeled, including nucleus reticularis lateralis, nucleus raphe magnus, pallidus and obscurus, the nucleus reticularis pontis oralis and caudalis, the paralemniscal nucleus and the dorsal and ventral parabrachial nuclei. At diencephalic levels, dense projections were seen from the parafascicular nucleus, dorsal premamillary nucleus, zona incerta, dorsomedial and ventromedial nuclei of the hypothalamus and the retrochiasmatic area, in the ventral portion of the anterior hypothalamus. At forebrain levels, occasional cells were seen in the medial preoptic area, lateral septum and the anterior cingulate cortex. Control injections of horseradish peroxidase into structures adjacent to the periaqueductal gray matter included three well localized deposits in the dorsal raphe. Retrogradely-labeled cells were found in lateral reticular nucleus of the medulla, nucleus raphe magnus, nucleus reticularis pontis caudalis, locus ceruleus, dorsal and ventral parabrachial nuclei, substantia nigra and the lateral hypothalamus. No labeled cells were found in the habenular nuclei. It is suggested that many of the descending hypothalamic and forebrain afferents may be relay centers for descending hippocampal formation efferents. Many of the periaqueductal gray afferent systems receive a direct projection from the hippocampal formation and could therefore coordinate influences from this limbic center with information on homeostatic mechanisms controlled by the hypothalamus. The numerous brainstem afferents to the periaqueductal gray could be involved in relay of ascending sensory information important for initiating any of several behavioral responses known to be controlled by the periaqueductal gray. In addition, certain raphe afferents might play a part in a feedback loop of the pain suppression circuit of which the periaqueductal gray is an important component.

Afferent Pathways↗
PubMed1982

Ventromedial nucleus of the hypothalamus: convergent excitatory and inhibitory responses to fimbria and stria terminalis stimulation.

Field and extracellular unitary potentials were recorded in the ventromedial nucleus of the hypothalamus (VMH) of urethane-anesthetized rabbits after stimulation of the fimbria and stria terminalis. Stimulation of the lateral portion of the fimbria, which carries fibers from the ventral subiculum of the hippocampal formation, evoked a two-component response. An early excitatory response, with an average latency of 10 msec, predominated along the lateral margins of the VMH. A later inhibitory potential with an average latency of 15 msec was seen predominantly within the central portions of the VMH. Stimulation of the dorsal component of the stria terminalis produced two similar response patterns: an early excitatory response with an average latency of 16 msec, followed by an inhibitory potential with an average latency of 25 msec. The topographical distribution of these two components of the response was nearly identical to that produced by lateral fimbria stimulation. In contrast, stimulation of the ventral component of the stria terminalis evoked a simple excitatory response with an average latency of 10 msec which was maximal within the core of the VMH. Extracellular unitary recordings showed that the early negativity associated with stimulation of each of these three pathways reflects a monosynaptic excitation of VMH cells and that there was convergence of the three excitatory inputs at the single cell level.

Afferent Pathways↗
PubMed1980

Characteristics of tetanic and post-tetanic potentiation in the septohippocampal and hippocampal commissural systems in the acute rabbit.

The frequency characteristics of tetanic and post-tetanic potentiation of the septohippocampal and hippocampal commissural systems were studied in the acute rabbit preparation. Glass micropipettes were employed to stimulate the medial septal (MSR) and contralateral CA1 (cCA1) regions. Extracellular postsynaptic potentials were recorded in the stratum radiatum and stratum oriens layers of dorsal CA1. Low frequencies of stimulation (2--12 Hz) and brief stimulus trains (7 or 16 stimuli) ensured that only short-term effects appeared in the data. With MSR and cCA1 stimulation, tetanic potentiation became pronounced at 4 Hz, and plateaued at 6--8 Hz. Thus potentiation was found to be pronounced within the range of the rabbit hippocampal theta rhythm. No differences were found in the characteristics of potentiation evoked by stimulation of MSR and cCA1. Post-tetanic potentiation lasting 6--12 sec was found. Again, potentiation characteristics did not depend on stimulus site, suggesting a common mechanism for the pathways studied. A two-factor mechanism was proposed to account for the post-tetanic potentiation data.

Animals↗
PubMed1977

Cholinergic mechanisms and short-term potentiation.

Acutely prepared rabbits were used to study, electrophysiologically, tetanic and post-tetanic potentiation of the pathway from the medial septal region to hippocampal field CA1. It was found that tetanic potentiation, evoked by short stimulus trains, was maximal at 6--8 Hz. Responses recovered from post-tetanic potentiation in 5--35 seconds. Acetylcholine, physostigmine, and cyclic GMP each had an excitatory effect on pyramidal cell responses when applied in stratum radiatum. The time course studies showed that these effects outlasted the duration of the injection current by many minutes. Phosphodiesterase inhibitors (e.g., isobutyl methyl xanthine) prolonged the time course of recovery with test responses which were post-tetanically potentiated. K+, on the other hand, selectively enhanced tetanic potentiation. It is suggested, with respect to the potentiation phenomena, that K+ acted primarily presynaptically to facilitate transmitter release, whereas cyclic GMP acted primarily postsynaptically for the enhancement of pyramidal cell excitability.

Acetylcholine↗