Jean-Jacques Vanderhaeghen

Coexistence of cholecystokinin and oxytocin-neurophysin in some magnocellular hypothalamo-hypophyseal neurons

SummaryThe existence of cholecystokinin in the posterior hypophysis and its hypothalamic origin have been unequivocally demonstrated. Immunocytochemical evidence is presented for the coexistence of gastrin-cholecystokinin and oxytocin-neurophysin I immunoreactivities in some magnocellular neurons of the supraoptic and paraventricular nuclei both in rat and bovine hypothalamus.

Cholecystokinins in the central nervous system and neurohypophysis.

Research on digestive peptides in brain started in 1975 with the discovery of peptides of the gastrin-cholecystokinin family in the brain of various vertebrates. Cholecystokinin octapeptide is largely distributed in the brain and neurohypophysis and its mapping has recently been reported by various authors. An up to data table summarizing CCK mapping is included. Cholecystokinin coexists with dopamine in some mesencephalic neurones and with oxytocin in some hypothalamic neurones. CCK immunoreactive fibers have been detected in the anterior commissura and in the corpus callosum especially after its surgical sectioning. CCK immunoreactive cell bodies are present in the nucleus septum lateralis, the nucleus of the bed of the stria terminalis and the nucleus preopticus medialis especially after direct colchicine injection into the cerebral hemispheres. Cholecystokinin is of importance in structures related to various physiological functions such as motricity, sensory mechanisms, endocrine and limbic systems. Consequently it should be interesting to study cholecystokinins in neurological disorders and in psychiatric conditions.

Inhibitory effect of cholecystokinin octapeptide on neurons in the nucleus tractus solitarius

Abstract We investigated the effect of the cholecystokinin octapeptide (CCK8) applied locally to neurons of the nucleus tractus solitarius (NTS). Results demonstrate an inhibitory effect of CCK8 on spike discharges including those related to respiration. It is suggested that CCK8 acts at this level through specific receptor mechanisms since CCK8-induced inhibitions were not reproduced by application of related peptides and were resistant to antagonists of different inhibitory transmitters.

CCK nerve terminals in the rat striatal and limbic areas originate partly in the brain stem and partly in telencephalic structures

After direct injection of colchicine into the rat rostral caudateputamen, levels of cholecystokinin-like immunoreactive (CCK-IR) material in this part of the nucleus are significantly lowered, and CCK-IR neuronal cell bodies are not demonstrable in the caudateputamen, although numerous ones are revealed in some adjacent telencephalic regions. Direct injection of kainic acid into the rostral caudate-putamen is not followed by a decrease of CCK-IR material in the lesioned region. Twenty one days after injection of 6-hydroxydopamine into the rat ventral mesencephalon, a significant decrease of CCK-IR material is observed in the frontal pole, the pyriform cortex, the nucleus accumbens and the ventral mesencephalon itself, but not in the caudate-putamen. After brain stem hemitransection, no decrease in CCK-IR material is observed in the rostral caudate-putamen.

Histochemical changes of substance P, FRAP, serotonin and succinic dehydrogenase in the spinal cord of rats with adjuvant arthritis

Various histochemical changes were found in spinal segments L4-L5 of rats with adjuvant arthritis, predominantly 30 days after inoculation. A slight to marked increase of substance P immunoreactivity occurred in laminae I, II and X. FRAP activity was enhanced in lamina II. Serotonin immunoreactivity was heavier in laminae I, VIII and IX in a few animals. The intensity of the histoenzymological reaction for succinic dehydrogenase increased in certain laminae VIII and X neurons. At day 15 of the disease the increase of substance P and FRAP activities was chiefly restricted to the medial portion of the superficial dorsal horn. There was a significant positive correlation between the scratching behaviour of arthritic rats and the substance P immunoreactivity in laminae X and I. If one accepts that scratching is pain-related, the data are consistent with a possible role of substance P in the chronic pain associated with adjuvant arthritis. They leave undetermined the significance of the other histochemical changes.

Cholecystokinin varies in the posterior pituitary and external median eminence of the rat according to factors affecting vasopressin and oxytocin

Using radioimmunoassay (RIA), the content of gastrin-cholecystokinin family peptide immunoreactivity (G-CCK-IR), in the posterointermediate lobe (PIL) of the rat pituitary, has been determined in several experimental conditions. G-CCK-IR levels are significantly higher in males than in females. Salt loading induces a significant decrease of G-CCK-IR in animals of either sex. In males, G-CCK-IR levels are lower than controls 21 days after either castration or daily subcutaneous oestradiol injections. Using immunocytochemistry, G-CCK-IR disappears from the external median eminence 21 days after adrenalectomy. Our results show that, in addition to sex difference, factors affecting the vasopressin and/or oxytocin levels in the posterior pituitary and external median eminence also affect G-CCK-IR in the same regions. Cholecystokinin may therefore be of importance in functions related to these hormones.

Reduced Cholecystokinin Levels in Cerebrospinal Fluid of Parkinsonian and Schizophrenic Patients Effect of Ceruletide in Schizophreniaa

The preliminary double-blind cross-over study does not indicate that ceruletide exerts antipsychotic action on schizophrenic patients free from neuroleptics. Because schizophrenia is an heterogenous disorder, a differential response to ceruletide in certain subtypes (particularly in acute cases) cannot be excluded at the present stage. A reduction of CCK levels is reported in the CSF of parkinsonian and schizophrenic patients free of neuroleptics. A double-blind cross-over study does not show that ceruletide has antipsychotic properties in neuroleptic-free patients suffering from schizophrenia.

Combined grafts of the ventral tegmental area and nucleus accumbens in oculo. Histochemical and electrophysiological characterization

SummaryDissection techniques and optimal donor stages have been established for constructing an isolated intraocular model of the ventral tegmental area (VTA)-accumbens system using intraocular sequential grafting. Single grafts including accumbens and VTA respectively survived and developed many organotypic features when taken from 15–17 day fetuses. Falck-Hillarp fluorescence histochemistry showed dopamine neurons and terminals in single VTA grafts, no or almost no catecholamine fibers in single accumbens grafts, and a well-developed VTA-accumbens dopamine pathway in combined grafts where cell bodies in the VTA part provided the accumbens part with a rich terminal network. A similar distribution was found using immunohistochemistry with antibodies directed against tyrosine hydroxylase. CCK-like immunoreactivity had a distribution that mimicked that of the catecholamine-containing system. Enkephaline-like immunoreactivity was found both in single VTA and in single accumbens pieces as well as in both parts of the double grafts. Cells with long-duration action potentials typical of dopamine neurons discharged at approximately 8 Hz in single VTA grafts and below 1 Hz in the VTA part of VTA-accumbens double grafts. Cells in the accumbens portion of double grafts had shorter action potential durations and fired at 10–20 Hz. Haloperidol increased discharge frequency in VTA neurons with long action potential durations while apomorphine reduced discharge markedly. Antidromic activation of putative dopamine neurons in the VTA part was obtained by electrical stimulation of the accumbens part. The indirect dopamine agonist + 3-methyl-phencyclidine slowed firing rates of neurons in the accumbens part of double grafts. Taken together, the histochemical and the electrophysiological data show that the intraocular VTA-accumbens system retains several of its normal structural and functional characteristics. It is proposed that the isolated VTA-accumbens projection can be used as a model to study the cellular mechanism of action of stimulant and opiate drugs of abuse.

Adenosine A2 Receptor Regulation of Striatal Gene Expression

Any perturbations within the basal ganglia system lead to movement disorders [1]. The striatum, receiving its main input from the cerebral cortex, is the first relay of this system, and its medium-sized spiny neurons give rise to the output pathways. Two subpopulations of these efferent GABAergic neurons have been identified. The neurons projecting to the globus pallidus, striatopallidal, express enkephalin and mostly the dopamine D2 receptor, whereas the neurons projecting to the susbtantia nigra pars reticulata, striatonigral, express substance P, dynorphin, and the dopamine D1 receptor [2]. These two subpopulations give rise to different loops, acting respectively as an inhibitory and an excitatory pathway to the thalamus [1]. In addition, two classes of interneurons mostly represent the remaining striatal neurons: the cholinergic and the somatostatin-expressing neurons.

Cholecystokinin in Brain and Hypophysis

Abstract Cholecystokinin, first digestive peptide found in the central nervous system, is synthesized there and possesses some characteristics of neurotransmitter and neuromodulator. Its large distribution makes it important for various cortical, limbic, hypothalamic, hypophyseal, motor and sensitive systems. It has close relationship with dopamine and various other peptides.