[Sclerosing polycystic adenosis of the parotid gland : surgical treatment of an extensive lesion of deep tissue without superficial damage]. / Adénose sclérosante polykystique de la parotide : traitement chirurgical d'une lésion extensive du lobe profond sans atteinte superficielle.

Sclerosing polycystic adenosis (SPA) is a rare benign epithelial lesion of the salivary glands, of unknown etiology, mainly affecting the parotid gland. We report the first clinical case of SPA involving the deep parotid gland with extension in the parapharyngeal space and the masticatory region. It has been resected by an external parotidectomy approach exclusively, despite the median extension of the lesion. The objective of this article is to complete the small series of cases described in the literature, and to update the knowledge of this rare disease.

L'adénose sclérosante polykystique (SPA) est une lésion épithéliale bénigne rare des glandes salivaires, d'étiologie inconnue, atteignant principalement la glande parotide. Nous rapportons le premier cas clinique de SPA dont l'origine est le lobe profond de la parotide et qui envahit la région masticatrice et l'espace parapharyngé. Elle a été réséquée par une voie d'abord externe de parotidectomie, exclusivement, malgré l'extension médiane de la lésion. L'objectif de cet article est de compléter la petite série de cas décrits dans la littérature, et d'actualiser les connaissances de cette pathologie rare.

Downregulation of amyloid precursor protein inhibits neurite outgrowth in vitro.

The amyloid precursor protein (APP) is a transmembrane protein expressed in several cell types. In the nervous system, APP is expressed by glial and neuronal cells, and several lines of evidence suggest that it plays a role in normal and pathological phenomena. To address the question of the actual function of APP in normal developing neurons, we undertook a study aimed at blocking APP expression using antisense oligonucleotides. Oligonucleotide internalization was achieved by linking them to a vector peptide that translocates through biological membranes. This original technique, which is very efficient and gives direct access to the cell cytosol and nucleus, allowed us to work with extracellular oligonucleotide concentrations between 40 and 200 nM. Internalization of antisense oligonucleotides overlapping the origin of translation resulted in a marked but transient decrease in APP neosynthesis that was not observed with the vector peptide alone, or with sense oligonucleotides. Although transient, the decrease in APP neosynthesis was sufficient to provoke a distinct decrease in axon and dendrite outgrowth by embryonic cortical neurons developing in vitro. The latter decrease was not accompanied by changes in the spreading of the cell bodies. A single exposure to coupled antisense oligonucleotides at the onset of the culture was sufficient to produce significant morphological effects 6, 18, and 24 h later, but by 42 h, there were no remaining significant morphologic changes. This report thus demonstrates that amyloid precursor protein plays an important function in the morphological differentiation of cortical neurons in primary culture.

A specific database for providing local and national level of integration of clinical data in cystic fibrosis.

It has recently been stated that a database is an essential tool in the management of CF. The purpose of this work is to create a specific database allowing optimal performance of storage, search and retrieval functions on patients with CF. A specific database was developed using a Windev licence, for application via Microsoft supported platforms or Intranet system. The database allows real-time point of care data management of medical, investigational and administrative data. It is currently being used in the 6 Belgian reference centres. It represents a useful tool for gathering information on routine clinical and lab data, bacteriology, treatments, complications and specific outcomes for clinical and research purposes. The ongoing evolution of the database includes enhancements toward research data orientation including comparison of patient data between different centres and completeness of the National CF registry questionnaire. A complimentary copy of the software can be provided to multidisciplinary accredited CF centres worldwide upon request.

Bronchial lipoma : an unusual cause of pleural empyema.

We report a case of rapidly growing pleural empyema due to endobronchial lipoma. The diagnosis was established by chest computed tomography (CT). Endobronchial lipoma is a rare benign tumor of the tracheobronchial tree which can cause irreversible damage to the distal lung parenchyma if diagnosis and treatment are not carried out in time.

Cloning and expression of human brain type I inositol 1,4,5-trisphosphate 5-phosphatase. High levels of mRNA in cerebellar Purkinje cells.

In brain and many other tissues, Type I inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase is the major isozyme hydrolysing the calcium-mobilizing second messenger InsP3. We recently reported the cloning and expression of dog thyroid InsP3 5-phosphatase. During the course of this cloning, screening of a human brain cDNA library allowed us to isolate a cDNA clone D1 with 91% sequence identity with the thyroid sequence. When clone D1 was expressed in Escherichia coli, the fusion protein had InsP3 5-phosphatase activity. M(r) estimates of the recombinant enzyme made by immunodetection, activity assay after SDS/PAGE or silver staining were consistent with the calculated molecular mass. In situ hybridization on human cerebellum sections localised the mRNA for this enzyme to the Purkinje cells.

ORL1, a novel member of the opioid receptor family. Cloning, functional expression and localization.

Selective PCR amplification of human and mouse genomic DNAs with oligonucleotides encoding highly conserved regions of the delta-opioid and somatostatin receptors generated a human DNA probe (hOP01, 761 bp) and its murine counterpart (mOP86, 447 bp). hOP01 was used to screen a cDNA library from human brainstem. A clone (named hORL1) was isolated, sequenced and found to encode a protein of 370 amino acids whose primary structure displays the seven putative membrane-spanning domains of a G protein-coupled membrane receptor. The hORL1 receptor is most closely related to opioid receptors not only on structural (sequence) but also on functional grounds: hORL1 is 49-50% identical to the murine mu-, delta- and kappa-opioid receptors and, in CHO-K1 cells stably transfected with a pRc/CMV:hORL1 construct, ORL1 mediates inhibition of adenylyl cyclase by etorphine, a 'universal' (nonselective) opiate agonist. Yet, hORL1 appears not to be a typical opioid receptor. Neither is it a somatostatin or sigma (N-allylnormetazocine) receptor. mRNAs hybridizing with synthetic oligonucleotides complementary to mOP86 are present in many regions of the mouse brain and spinal cord, particularly in limbic (amygdala, hippocampus, septum, habenula, ...) and hypothalamic structures. We conclude that the hORL1 receptor is a new member of the opioid receptor family with a potential role in modulating a number of brain functions, including instinctive behaviours and emotions.

Distribution of the neurons containing inositol 1,4,5-trisphosphate 3-kinase and its messenger RNA in the developing rat brain.

As a result of its interaction with a specific receptor, inositol 1,4,5-trisphosphate (InsP3) mobilizes intracellular calcium. The metabolism of InsP3 is rather complex: InsP3 3-kinase produces Inositol 1,3,4,5-tetrakisphosphate (InsP4), a putative second messenger also involved in the intraneuronal calcium homeostasis. The distribution of the messenger RNA coding for the recently cloned InsP3 3-kinase was studied in the developing rat brain by using oligonucleotides derived from the rat cDNA sequence and in situ hybridization combined with Northern blot analysis. In addition, the locations of the enzyme were determined by immunohistochemistry in combination with Western blot analysis. By Northern blot and Western blot analyses on rat brain, the kinase was not detected in the embryo, was first found slightly at birth, and reached adult levels around 2-3 postnatal weeks. These findings were confirmed in the different positive regions by in situ hybridization conducted at the macroscopic level. At the cellular level, the mRNA was found exclusively in the neuronal populations previously demonstrated in the adult. The levels of transcripts per neuron were however higher in the adult than in the neonate brain. The enzyme mRNA could be detected first at postnatal day 0, (birth, P0) in the perikarya of the cerebellar Purkinje cells, followed at P4 by the hippocampal CA1 pyramidal cells and granule cells of the dentate gyrus and finally, at P9, by a majority of the neurons in the cortical layers II-III and V, especially in the frontal cortex and cingulate cortex; claustrum; caudate, putamen, accumbens, olfactory tubercle and calleja islets; anterior olfactory nucleus; taenia tecta; piriform piriform cortex; dorsolateral septum; bed nucleus stria terminalis; amygdala; hippocampal CA2-4 sectors and subiculum. By immunohistochemistry, the enzyme was initially found in the periphery of the cell bodies of the neonatal neurons; was progressively enriched in the developing dendritic arborization during the first postnatal weeks where it remained exclusively localized in the adult. In conclusion, in the developing brain, InsP3 3-kinase was first detected at birth, and thereafter its concentrations increased to reach adult levels around 2-3 postnatal weeks. At the cellular level, the kinase was exclusively found in the neurons. The small amounts of transcripts found per neuron in the neonate increase during synaptogenesis and the protein became progressively enriched in the developing dendritic arborization, where it is localized in the adult.

Fatal familial insomnia: clinical and pathologic study of five new cases.

In 1986, we reported two anatomoclinical observations of a familial condition that we called "fatal familial insomnia" (FFI). We now present the pedigree as well as the clinical and neuropathologic findings in five new subjects. The pedigree includes 288 members from six generations. Men and women are affected in a pattern consistent with an autosomal dominant inheritance. The age of onset of the disease varies between 37 and 61 years; the course averages 13 months with a range of 7 to 25 months. Progressive insomnia (polygraphically proven in two cases); autonomic disturbances including hyperhidrosis, hyperthermia, tachycardia, and hypertension; and motor abnormalities including ataxia, myoclonus, and pyramidal dysfunction, were present in every case, but with variable severity and time of presentation. Sleep and autonomic disorders were the earliest signs in two subjects, motor abnormalities were dominant in one, and others had intermediate clinical patterns. Pathologically, all the cases had severe atrophy of the anterior ventral and mediodorsal thalamic nuclei. Other thalamic nuclei were less severely and inconsistently affected. In addition, most of the cases had gliosis of the cerebral cortex, a moderate degree of cerebellar atrophy with "torpedoes," and severe atrophy of the inferior olivary nuclei. One case also showed spongy degeneration of the cerebral cortex. We conclude that all the lesions were primary, and that FFI is a multisystem disease in which the different structures are primarily affected with different severity. The insomnia appears to correlate best with the major thalamic pathology. The possibility that FFI belongs to the group identified as prion diseases or diseases transmitted by unconventional agents is examined.

Distribution of neuronal cannabinoid receptor in the adult rat brain: a comparative receptor binding radioautography and in situ hybridization histochemistry.

The neuronal distribution of cannabinoid receptor in the adult rat brain is reported, combining receptor binding radioautography using the synthetic psychoactive cannabinoid ligand CP55,940 with in situ hybridization histochemistry using oligonucleotide probes complementary to rat cannabinoid receptor cDNA. In the cerebral cortex, especially in the frontal and cingulate cortex, dense binding was found in layers I and VI together with slight mRNA levels in a majority of both pyramidal and non-pyramidal-shaped neurons and of high mRNA levels in a moderate number of non-pyramidal-shaped neurons especially in layers II-III and V-VI. In the hippocampal dentate gyrus, very dense staining was found in the molecular layer together with high mRNA levels in a moderate number of hilar neurons close to the granular layer. In Ammon's horn, especially in the CA3 sector, very dense binding was found in the dendritic layers together with slight mRNA levels in the majority of the pyramidal cells and high mRNA levels in a moderate number of interneurons. In the basal ganglia, binding was very dense in the lateral putamen, substantia nigra pars reticulata, globus pallidus and entopeduncular nucleus, moderate in the medial putamen and caudate; and slight in the accumbens, together with slight to moderate mRNA levels in the striatal medium-sized neurons. Together with slight binding, slight to moderate mRNA levels were found in the majority of the neurons in the subthalamic nucleus. No binding and mRNA were found in the substantia nigra pars compacta and ventral tegmental area. Slight to moderate binding was found together with slight to moderate mRNA levels in the majority of neurons in the anterior olfactory nucleus; septum, especially medial septum and diagonal band of Broca; amygdala, especially basolateral amygdala; lateral habenula; ventromedial hypothalamic nucleus; lateral interpeduncular nucleus; central gray, dorsal cochlear nucleus; parabrachial nucleus; dorsal pontine tegmentum; pontine nuclei; commissural part of the nucleus tractus solitarius; inferior olive and dorsal horn of the spinal cord. In the cerebellum, very dense binding was found in the molecular layer together with slight mRNA levels in the majority of the granule cells and moderate mRNA levels in the basket and stellate cells. In conclusion, this study provides, for the first time, indirect assessment of the neurons containing cannabinoid receptor in the entire adult rat brain and will serve as a basis for future direct morphological confirmation using receptor immunohistochemistry and for functional studies.

Immunohistochemical distribution of neurons containing the G-proteins Gq alpha/G11 alpha in the adult rat brain.

A new class of G-proteins, the Gq family, has been recently identified and found to be involved in phospholipase C activation. The alpha subunits of the Gq and G11 members of this family are separate polypeptides but appear to have the same function. In this study, the cellular distribution in the adult rat brain of these G-proteins, Gq alpha/G11 alpha, was determined by immunohistochemistry using an antipeptide antiserum directed against the predicted C-terminal decapeptide which is conserved between these polypeptides. The specificity of the antiserum was verified by Western blot analysis using rat brain homogenates. Immunoreactivity was detected in neurons, where it was localized in the dendrites and at the periphery of the cell bodies. The staining was abundant in the dendrites of cerebellar Purkinje cells and hippocampal CA1 pyramidal cells. Staining was also found in neurons in the olfactory bulb, minor and major islets of Calleja, anterior olfactory nuclei and piriform cortex; the different cortical areas especially in their superficial layers; caudate-putamen, accumbens and olfactory tubercle; lateral septum and amygdala; hippocampal CA2-4 sectors of Ammon's horn, dentate gyrus and hilus; hypothalamic supraoptic nucleus; cerebellar granular layer; colliculi and superficial layers of the dorsal horn of the spinal cord. In conclusion, the brain neuronal localizations of Gq alpha/G11 alpha match that of phospholipase C, 1,4,5-triphosphate receptor and, to a lesser extent 1,4,5-triphosphate-3-kinase.

Comparison of neuronal inositol 1,4,5-trisphosphate 3-kinase and receptor mRNA distributions in the adult rat brain using in situ hybridization histochemistry.

As a result of its interaction with a specific receptor, inositol 1,4,5-trisphosphate mobilizes intracellular calcium. The metabolism of inositol 1,4,5-trisphosphate is rather complex: inositol 1,4,5-trisphosphate 3-kinase produces inositol 1,3,4,5-tetrakisphosphate, a putative second messenger. In order to elucidate inositol 1,3,4,5-tetrakisphosphate function, a comparative in situ hybridization study of the distributions of inositol 1,4,5-trisphosphate 3-kinase and receptor mRNAs was performed in the adult rat brain using oligonucleotides derived from their cDNA sequences. The neuronal distributions of the mRNA for the receptor were larger than for the kinase. Highest levels of both mRNAs were found in the cerebellar Purkinje cells, where they were enriched in their neuronal perikarya and to a lesser extent in their dendrites. In addition to the cerebellum, mRNAs were mainly detected in the hippocampal pyramidal cells of the CA1 sector of the Ammon's horn and in the granule cells of the dentate gyrus, and also in a majority of the neurons in the cortical layers II-III and V, especially in the frontal cortex and cingulate cortex; caudate-putamen, accumbens, olfactory tubercle and Calleja islets; claustrum; anterior olfactory nucleus; taenia tecta; piriform cortex; dorsolateral septum; bed nucleus stria terminalis; amygdala; hippocampal CA2-4 sectors and subiculum. The inositol 1,4,5-trisphosphate receptor mRNA but not kinase mRNA was found in a majority of the neurons in the thalamus, especially in the parafascicular nucleus; hypothalamus, especially the medial hypothalamus; substantia nigra pars compacta and ventral tegmental area; superior colliculus; lateral interpeduncular nucleus and central gray. Taking into account the limitation in sensitivity of the technique, both mRNAs were not detected in glial cells and in the olfactory bulb; basal nucleus of Meynert, diagonal band nuclei; medial septal nucleus; substantia innominata; globus pallidus; entopeduncular nucleus; substantia nigra pars reticulata; ventral pallidum; subthalamic nucleus; spinal cord and dorsal root ganglia. In conclusion, cerebellum and hippocampus appear to contain almost similar levels of kinase mRNA. This is in contrast to receptor mRNA levels which were at much higher levels in the cerebellum when compared with the hippocampus. For this reason, we have chosen hippocampal CA1 pyramidal cells and dentate gyrus granule cells for studying inositol 1,4,5-trisphosphate 3-kinase function.

Homolateral cerebrocortical changes in neuropeptide and receptor expression after minimal cortical infarction.

A cortical infarct of 2 mm diameter was obtained in the parietal cortex after a craniotomy, disruption of the dura mater and topical application of 3 M KCl. It has been shown previously that the presence of a small cortical infarct induces an increase in immediate early gene messenger RNA expression followed by an increase in neuropeptide and glutamic acid decarboxylase messenger RNA expression. Glutamate, acting at N-methyl-D-aspartate receptors, is held responsible for these changes, since they are blocked by pretreatment with dizocilpine. In the present study, we have analysed the consequences of the dramatic changes in messenger RNA expression on the level of immediate early gene products c-fos and zif 268, and on that of neuropeptides by using immunohistochemistry. After just 1 h, an increase in c-fos- and zif 268-like immunoreactivity is observed in the entire cortical hemisphere homolateral to the infarct, and is no longer detected after 6 h. An increase in cholecystokinin octapeptide-, substance P-, neuropeptide Y- and somatostatin-like immunoreactivity is observed in the entire cortical hemisphere homolateral to the infarct after three days, and is no longer detected after 30 days. To investigate if these dramatic increases in neuropeptide immunoreactivities may have functional consequences, we studied the level of cholecystokinin receptors by autoradiographic binding using [125I]cholecystokinin-8S and in situ hybridization for the detection of cholecystokinin-b receptor messenger RNA. A decrease in cholecystokinin binding sites and cholecystokinin-b receptor messenger RNA is observed in the entire cortical hemisphere homolateral to the infarct after three days, and is no longer detected after nine days. This study shows that a topical stimulation has diffuse effects, reaching regions far from the site of the lesion, and some of them are still strongly present after nine days. The increase in neuropeptide messenger RNAs is followed by an increase in the protein products of these genes, which may modify the neurotransmission. As a corollary to this, a decrease in cholecystokinin binding sites occurs. This may have further consequences on signal transduction pathways. This decrease in cholecystokinin binding sites is associated with a decrease in the cholecystokinin-b receptor messenger RNA, and this is the first example of a decrease in messenger RNA levels in this experimental model.

Homolateral cerebrocortical increase of immediate early gene and neurotransmitter messenger RNAs after minimal cortical lesion: blockade by N-methyl-D-aspartate antagonist.

A small surgical lesion of the parietal cortex induces an increase in the expression of several messenger RNAs varying from 172 to 980% in the entire homolateral cerebral cortex, as detected by quantitative in situ hybridization histochemistry. The messenger RNAs encoding the immediate early genes of the leucine zipper family (c-fos, c-jun, jun-B), the Zinc finger family (zif268), the glucocorticoid receptor family (NGFI-B) and the interferon family (PC4) are increased within 2 h after the lesion and return to normal levels at 6 h. The messenger RNAs encoding cholecystokinin, neuropeptide Y, somatostatin and the synthetizing enzyme of the neurotransmitter GABA, glutamate decarboxylase, are elevated within one day and return to normal levels after six days. An intraperitoneal injection of the N-methyl-D-aspartate receptor antagonist dizocilpine maleate, 30 min before surgery, prevented either the induction of immediate early gene expression or the increase of neuropeptide and glutamate decarboxylase messenger RNA expression. This study demonstrates that a minimal cortical lesion induces extensive changes in gene expression and that the mechanism(s) leading to these changes involves the action of glutamate at the N-methyl-D-aspartate receptor. These modifications may be of importance in explaining diffuse changes not related to neuronal circuitry in several conditions.

Substance P neurons in the human hippocampus: an immunohistochemical analysis in the infant and adult.

An analysis of the distribution of substance P immunoreactive nerve cell bodies and fibres is given for infant and adult human hippocampus by using the peroxidase-antiperoxidase technique of Sternberger. The description covers the substance P distribution in the area dentata, the Ammon's horn, the subicular complex and the entorhinal cortex. Each region shows a specific pattern in its substance P immunoreactivity. In general, the hippocampal neurons occur in three major classes of interneurons: large (20-35 microns) horizontal bipolar or multipolar neurons in the alveus, in the deep part of the subicular complex, the entorhinal cortex, and in the white matter of the angular bundle; small (10-20 microns) and large (20-35 microns) vertically oriented bipolar or multipolar neurons in the stratum oriens, in the stratum pyramidale of the Ammon's horn, and in the deep part of the subicular complex and the entorhinal cortex; large (20-35 microns) multipolar neurons in the hilus. Substance P immunoreactive fibres are particularly abundant around pyramidal cells of the CA2 and CA3 subfields of the Ammon's horn and around granule cells of the area dentata. They are also detected in the fimbria and angular bundle. Comparative study of the infant and adult hippocampus reveals no variation in the area dentata and Ammon's horn except that substance P immunoreactive fibres are more abundant in the molecular layer of the area dentata in adults. In contrast, a far more extensive number of substance P immunoreactive cell bodies are detected in the deep layers of the subicular complex and the entorhinal cortex, as well as in the white matter of the angular bundle in infants aged between three and 12 months old. This rich substance P immunoreactive network raises questions concerning its function within the human hippocampus.

Localization of the two protein kinase C beta-mRNA subtypes in cat visual system.

Protein kinase C (PKC) consists of a family of different subtypes encoded by different PKC genes. We investigated the distribution of PKC beta 1 and PKC beta 2 in the visual system of the adult cat by in situ hybridization using oligonucleotide probes complementary to the PKC beta 1 and PKC beta 2 mRNAs, two splicing variants of the same gene transcript. In the primary visual cortex PKC beta 1 and PKC beta 2 were both present. The laminar distribution patterns found for the two PKC subtypes were identical. A remarkable finding was the difference between the laminar distribution of the PKC beta s in areas 17 and 18 when compared with area 19. In all three areas the highest expression levels were found in layer VI, moderately high levels were found in layers II, III and V, while layer I was devoid of signal. In area 17 and 18 layer IV stood out by its low PKC beta signal. In sharp contrast, layer IV of area 19 was indiscernible from the superficial layers because of an evenly high signal. In the dLGN of the adult cat PKC beta 1 and PKC beta 2 mRNAs were distributed rather homogeneously over the different layers, but the expression levels for PKC beta 1 were clearly higher than those for PKC beta 2.

Neurotensin containing neurones in the human hippocampus of the adult and during development.

Marked age-related changes are noted in the neurotensin distribution of the human hippocampus. Different neuronal structures containing neurotensin are detected by immunohistochemistry during postnatal brain growth from birth to 4 years but no later. They are the neurotensin-immunoreactive pyramidal cells of the subiculum and presubiculum. Their axonal fibres are seen in the alveus and the fimbria. There are also the neurotensin-immunoreactive granular cells of the hilus. The varicosities of the mossy fibres are detected among the pyramidal cells of the CA3 and CA2 subfields of the Ammon's horn. After 4 years of age, only the varicosities are shown by immunohistochemistry, thus there is probably an important decrease in the neurotensin concentration in the cell bodies of the granular cells and also in the pyramidal neurons of the subiculum and presubiculum.

High concentration of somatostatin-14 neurones in the infant human hippocampus.

The distribution of somatostatin-14 immunoreactivity (SRIF-14-IR) was studied in the hippocampal formation of the human infant. The most prominent accumulation of SRIF-14-IR cell bodies and processes occurred in the CA1 subfield of the stratum oriens in the Ammon's horn, in the hilus of the area dentata, in the deeper layers of the subicular complex and in the entorhinal cortex. SRIF-14-IR neurones are also detected in the angular bundle though they are rare in the alveus and absent in the fimbria.

Transient neurotensin in the cat inferior olive during development.

By immunohistochemistry, a large number of neurotensin immunoreactive nerve terminals are found in the kitten inferior olive of the medulla oblongata. They are present in the dorsal lamella of the principal olive, in the ventrolateral outgrowth and in the medial part of the caudal dorsal accessory olive. They are absent in the medial accessory olive. They disappear in the adult cat. Neurotensin immunoreactivity is absent in the developing rat inferior olive. This localization in the cat suggests a neuronal origin in the mesencephalon, mainly in the red nucleus. These results confirm our recent report on a transient large neurotensinergic innervation of the human developing principal olive.

Cholecystokinin distribution in the human striatum and related subcortical structures.

The distribution of cholecystokinin immunoreactive nerve cell bodies and processes is reported in the human striatum and adjacent structures such as the claustrum, the pallidum, the bed nucleus of the stria terminalis and the substantia innominata. Cholecystokinin-positive terminals are present in the striatum where they are arranged in a patchy pattern. Cholecystokinin-positive somata are observed in the claustrum and in the bed nucleus of the stria terminalis but not in the striatum, the pallidum or the substantia innominata. Dense networks of cholecystokinin-positive woolly fibres are present in the bed nucleus of the stria terminalis and the substantia innominata. These results suggested that cholecystokinin is involved in the compartmental organization of the human striatum. This compartmentalization has functional and pathological implications. Involvement of the cholecystokinin system in some basal ganglia diseases is therefore expected. Presence of neuronal cholecystokinin in the accumbens nucleus, bed nucleus of the stria terminalis and substantia innominata also suggests that this peptide may interact at different levels in the human limbic system.

Activation of multiple transcription factor genes by tetrahydrocannabinol in rat forebrain.

delta-9-Tetrahydrocannabinol (THC) is a major psychoactive component of cannabis. We have recently localized a receptor for THC in the forebrain and found in the caudate-putamen that its gene expression is modulated by glucocorticoids, dopamine and glutamate. Here, we report for the first time, using quantitative in situ hybridization, that acute THC (5 mg kg-1, i.p.) regulates the mRNA levels of multiple immediate early genes in the adult rat forebrain. Twenty minutes after a single THC injection, significant increases in concentration of the mRNAs for C-FOS, C-JUN and ZIF-268 were observed in the cingulate cortex (75, 45 and 37%) and for C-FOS and ZIF-268 in the fronto-parietal cortex (60 and 64%) and caudate-putamen (81 and 32%) while JUN-D mRNA levels were not changed. These transcription factor genes might mediate putative THC modulation of neurotransmitter gene expression.