Parkinson's disease: From bench to bedside.

Parkinson's disease is a very complex public health problem with different etiologies and a wide range of clinical features including motor and non-motor symptoms. The aim of the current report is to review the latest advances in the understanding of PD etiologies, diagnosis, epidemiology and an overview of the earlier and latest advances in the management of PD, from L-DOPA to adult astroglia reprogramming into dopaminergic neurons in vivo.

The underlying physiological basis of the desert rodent Meriones shawi's survival to prolonged water deprivation: Central vasopressin regulation on peripheral kidney water channels AQPs-2.

Meriones shawi (M. shawi) is a particular semi-desert rodent known by its resistance to long periods of thirst. The aim of the present investigation is to clarify the underlying mechanisms allowing M. shawi to resist to hard conditions of dehydration. For this reason we used two different approaches: i) a morphometric study, which consists in measuring the effect of dehydration on body and kidneys weights as well as the report kidney weight/body weight, ii) By immunohistochemistry, we proceed to study the effect of dehydration on the immunoreactivity of central vasopressin (AVP) and the kidney aquaporin-2 (AQP-2) which is a channel protein that allows water to permeate across cell membranes. Our results showed both a body mass decrease accompanied by a remarkable kidneys hypertrophy. The immunohistochemical study showed a significant increase of AQP-2 immunoreactivity in the medullar part of Meriones kidneys allowing probably to Meriones a great ability to water retention. Consistently, we demonstrate that the increased AQP-2 expression occurred together with an increase in vasopressin (AVP) expression in both hypothalamic supraoptic (SON) and paraventricular nucleus (PVN), which are a major hub in the osmotic control circuitry. These various changes seen either in body weight and kidneys or at the cellular level might be the basis of peripheral control of body water homeostasis, providing to M. shawia strong resistance against chronic dehydration.

Dehydroepiandrosterone sulphate improves cholestasis-associated fatigue in bile duct ligated rats.

Fatigue is a common debilitating symptom in patients with primary biliary cirrhosis (PBC). The mechanism of fatigue is still poorly understood. However, it has been reported that levels of the steroid dehydroepiandrosterone sulphate (DHEAS) are reduced in plasma of patients with PBC, and substitutive therapy has been suggested to improve fatigue symptoms experienced during the course of this disease. In this study, we tested the effect of DHEAS on whole body fatigue in rats following bile duct ligation (BDL). Fatigue was estimated by the time spent on an electrified grid as a result of falling off a treadmill and by performance of rats on an infrared beam monitor which allows the assessment of travelled distance and stereotypic movement activities. On day 5 after BDL surgery, cholestatic rats exhibited increased whole body fatigue as reflected by significantly increased time spent on the electrified grid, reduced travelled distance and reduced stereotypic movements. Administration of 5 mg kg(-1) of DHEAS to BDL rats for three consecutive days significantly normalized their behaviour. Fatigue scores were also found to be reduced in cirrhotic rats 4 weeks after BDL surgery, and DHEAS treatment for 3 days reduced fatigue scores at this stage. Dehydroepiandrosterone sulphate treatment was sufficient to increase brain levels of DHEAS in the BDL rats in a manner that is significantly and highly correlated with those of plasma DHEAS and brain dehydroepiandrosterone (DHEA). Substitutive therapies with DHEAS or DHEA could represent novel approaches in the management of fatigue due to cholestasis-induced liver failure.

Immunohistochemical evaluation of the effect of lead exposure on subcommissural organ innervation and secretion in Shaw's Jird (Meriones shawi).

The secretory activity of subcommissural organ cells is controlled by various extrinsic and intrinsic factors. Lead has been recognised as a neurotoxic heavy metal, since it induces morphological and functional abnormalities in the brain. In this work, we examined the effect of lead exposure on the subcommissural organ (SCO), a brain gland known by its secretion of Reissner's fiber (RF) in cerebro-spinal fluid. Glycoprotein secretion and serotonin (5HT) innervation of the SCO was examined after acute and chronic lead exposures in the sub-desert rodent Meriones shawi. Lead exposures were achieved by, respectively, intra-peritoneal injection of 25 mg/kg body weight of lead acetate for 3 days and 0.5% of lead acetate in the drinking water over 4 months until adult age. 5HT and RF immunolabeling in the SCO revealed several serotoninergic fibers reaching the SCO and abundant secretory material. An increase in both 5HT innervation and secretory material of the SCO was recorded after both acute and chronic lead exposure. These results show that lead exposure affects the serotonergic innervation of the SCO. Moreover, the enhancement of SCO secretion suggests a role of this gland in neuroprotection and lead detoxification of the brain in Meriones shawi.

Proliferative activity and nestin expression in periventricular cells of the adult rat brain.

Mitotic activity in the forebrain subventricular zone is well documented but only in vitro reports suggest the presence of multi-potent stem cells all along the adult mammalian neuraxis. We demonstrate, following cerebroventricular infusion of labeled nucleotides in rat brain, a mitotic activity in the choroid plexus, the ependymal and subependymal layers of the mid- and hindbrain. This proliferation, which probably enables renewal of these structures, was unaffected by the destruction of their serotonergic innervations. Nestin, a marker of immature neural cells, was observed in some proliferative subependymal cells, some classical ependymocytes and in the specialized ependymocytes of the subcommissural organ, the collicular recess and the tanycytes. These observations indicate the presence of immature proliferative cells in the third and fourth periventricular structures, which may generate neural cells.

Postnatal secretion of the subcommissural organ of the Meriones shawi: control of serotonin innervation.

The postnatal development of the subcommissural organ (SCO) glycoprotein secretion in form of Reissner's fiber and the putative control of the serotonin innervation upon the SCO activity were examined by immunohistochemistry in the semi-desert rodent, Meriones shawi. Abundant SCO secretory material and numerous serotoninergic fibers reaching the SCO were observed in newborns meriones. An increase of both secretory material and serotonin fibres density inside the SCO was observed during postnatal period and into adulthood. Neurotoxic destruction with 5,7-dihydroxytryptamine of the SCO serotonin input in the adult or the inhibition of serotonin synthesis by para-chlorophenylalanine at different postnatal ages, resulted in a decrease of the intensity of SCO Reissner's fiber immunolabelling suggesting a reduction in the SCO secretory material. This result might reflect either an inhibition of the synthesis or a stimulation of release of secretory material. These data suggest that serotonin innervation could be precociously involved in the regulation of the merione SCO secretion.

Differences in protein expression in the subcommissural organ of normal and lordotic lizards (Agama impalearis).

Lordosis, a skeletal malformation, is characterized by abnormal curvature of the vertebral column. Involvement of the subcommissural organ (SCO) in the correct development of the axial skeleton via the thread-like Reissner's fiber (RF) has been suggested. However, the functional significance of the SCO and RF in these mechanisms remains, to date, little understood. To detect eventual changes in the SCO of reptiles bearing a naturally occurring skeletal malformation, we aimed here at investigating with immunohistochemistry RF glycoprotein and immediate early gene expression in the SCO of normal and lordotic lizards. In normal lizards, RF immunoreactivity was evident in the apical and basal domains of SCO cells. In specimens derived from lordotic animals, RF-immunoreactive material filled all SCO cell portions, and numerous large droplets were observed in the basal part of the organ. Cell nuclei exhibiting immunoreactivity to the protein product of the gene c-fos were evident in basal SCO cells of lordotic animals, whereas Fos immunoreactivity was absent in the SCO of normal lizards. The changes detected in RF immunoreactivity and Fos induction in SCO cells of lordotic animals favor the occurrence of changes in the secretory activity and gene expression of SCO cells. The present data further demonstrate modifications occurring in the SCO secretory material in skeletal malformed vertebrates, and support a relationship of such changes with the malformed state of these animals.

Secretory activity and serotonin innervation of lizard's subcommissural organ.

We investigated immunohistochemically the subcommissural organ (SCO) glycoprotein secretion, its serotoninergic (5-HT) innervation and the possible control of this innervation upon the SCO activity in lizards (Agama impalearis, Saurodactylus mauritanicus and Eumeces algeriensis). Inside the SCO, interspecific differences in the intensity and the distribution of both secretory product and 5-HT nerve fibers were observed. Compared with Agama and Eumeces, the SCO of Saurodactylus displayed intense secretory products and several 5-HT fibers. In Saurodactylus, i.p. injection of parachlorophenylalanine, a potent inhibitor of 5-HT synthesis, produced a marked decrease of SCO secretory product. We report in this study species differences of the lizard SCO secretory activity and its possible physiological control by 5-HT innervation, as previously demonstrated in mammals.

Secretory activity and serotonin innervation of subcommissural organ.

We investigated immunohistochemically the subcommissural organ (SCO) glycoprotein secretion, its serotoninergic (5-HT) innervation and the possible control of this innervation upon the SCO activity in lizards (Agama impalearis, Saurodactylus mauritanicus and Eumeces algeriensis). Inside the SCO, interspecific differences in the intensity and the distribution of both secretary product and 5-HT nerve fibers were observed. Compared with Agama and Eumeces, the SCO of Saurodactylus displayed intense secretory products and several 5-HT fibers. In Saurodactylus, i.p. injection of parachlorophenylalanine, a potent inhibitor of 5-HT synthesis, produced a marked decrease of SCO secretory product. We report in this study species differences of the lizard SCO secretory activity and its possible physiological control by 5-HT innervation, as previously demonstrated in mammals.

GABA uptake and phenotypic characteristics of the subcommissural ependymocytes of the semi-desertic rodent, Meriones shawi: correlation with serotoninergic innervation.

Many studies have emphasized species differences in the serotoninergic innervation and phenotypic characteristics of the subcommissural organ in mammals. The post-natal distribution patterns of serotonin-containing fibers, the onset of gamma-aminobutyric acid uptake, and glial markers have been studied in the subcommissural organ of the semi-desertic rodent, Meriones shawi, by using immunohistochemical and autoradiographic techniques. Abundant serotoninergic fibers can be observed in the subcommissural organ of the newborn Meriones, some of them running among the ependymocytes and reaching the apical part of this organ. During the first 2 post-natal weeks of development, the subcommissural organ displays a progressive increase of serotonin fiber density throughout the organ, including the apical part. The existence of a dense serotonin-containing basal plexus concomitantly with a high apical innervation in this organ is a specific characteristic of Meriones. Ependymocytes of this organ have the ability to take up gamma-aminobutyric acid at birth. This uptake decreases and completely disappears from the 2nd week. The reappearance of gamma-aminobutyric acid accumulation in ependymocytes of the adult subcommissural organ after destruction of the serotonin innervation by a neurotoxin (5-7 dihydroxytryptamine) suggests an inhibitory effect of the serotonin innervation on this accumulation. Immunohistochemical studies of the phenotype of the ependymocytes with respect to glial markers during ontogeny show the transitory expression of glial fibrillary acidic protein, the presence of vimentin and the absence of S100 protein expression. No correlation has been found between the serotonin innervation and the expression of the glial markers.

Distribution of GABA immunoreactive systems in the forebrain and midbrain of the chameleon.

An immunocytochemical method, using glutaraldehyde fixation and an antiserum developed against a GABA-glutaraldehyde protein conjugate, permitted direct visualization of GABAergic structures in the brain of a reptile (chameleon). GABA immunoreactive cell bodies and nerve terminals were observed to be evenly distributed throughout the forebrain and midbrain. In the forebrain, GABA-positive perikarya were shown in all cortical areas, the septal area, the striatum, the dorsal ventricular ridge, and in the nucleus accumbens. In the midbrain, the optic tectum contained a dense and laminar distribution of GABA neurons. These neurons were also observed in the lateral geniculate nucleus, nucleus profundus mesencephali, nucleus opticus tegmenti and substantia nigra. Immunoreactive nerve fibers and terminals were observed in the same structures and, additionally, in the tractus septo-hypothalamicus, habenula complex, median eminence, intermediate lobe of the pituitary, basal part of the subcommissural organ, torus semicircularis and nucleus reticularis isthmi. These results provide a framework for a further electron microscopic analysis of the GABAergic innervation of some encephalic areas involved in physiological regulations particular to this species especially the visual system.

The distribution of 5-HT immunoreactive systems in the brain of a saurian, the chameleon.

The distribution of serotonin immunoreactive cell bodies and fibers was studied in the chameleon brain by using the immunohistochemical technique with antisera against serotonin coupled to a carrier with glutaraldehyde. Serotonin perikarya were found in the caudal midbrain tegmentum, in the lateral part of the nucleus reticularis isthmi, the lateral part of the nucleus interpeduncularis and along the midline in the raphe superior. More caudally, the serotonin immunoreactive cell bodies were located along the nucleus raphe inferior and ventrolaterally in the vicinity of the olivary complex. No immunoreactive cell bodies were found in the spinal cord nor in the paraventricular organ (PVO) of the hypothalamus. Immunoreactive fibers were observed in the entire brain. Prominent concentrations were found in the dorsal cortex, lateral septum, lateral geniculate nucleus, median eminence, pretectal nucleus, nucleus interpeduncularis, vestibular nucleus and olivary complex. Descending serotonin immunoreactive fibers were found in particular in the ventral motoneuron area in the spinal cord. One of the most interesting findings in this study was the lack of immunoreactive CSF contacting neurons in the PVO and the observation of an extensive plexus of supraependymal fibers, a feature reported so far only in mammals.

Distribution of dopamine immunoreactive systems in brain stem and spinal cord of the chameleon.

An immunohistochemical method, using glutaraldehyde fixation and a highly specific monoclonal antibody recently synthetized against dopamine (DA)-glutaraldehyde protein conjugate, permitted direct visualization of DA structures in the brainstem and spinal cord of a reptile (Chameleon). DA-immunoreactive cell bodies occurred in some contiguous areas of the midbrain tegmentum. The first one was located in the ventral tegmental area. Some somata intermingled with the oculomotor nucleus. The second group was the large round or oval DA-Immunostained neurons located in the substantia nigra. More caudally, a third group of round or fusiform DA-cell bodies was seen in an homologous area of so called mammalian A8 and were continuous with the substantia nigra group. In the medulla oblongata, the DA-containing cells were shown in the nucleus of solitary tract and in the dorsal lateral part of the dorsal motor nucleus of the vagus. The density of this DA-Immunoreactive neurons decreased more caudally. At the medullo-spinal level and upper cervical spinal cord, a few labelled cells were distinguished near the central canal. In the spinal cord DA-immunopositive cell bodies were observed in the vicinity of the central canal and formed a continuous column that extended throughout the rostral spinal cord. The apical processes of these neurons seemed to be in contact with the lumen of the central canal. This study constitute the first visualization of the immunoreactive DA-cell bodies at the medullo-spinal level which were already described, as TH immunoreactive in other species of reptiles.

Existence of a GnRH immunoreactive nucleus in the dorsal midbrain tegmentum of the chameleon.

The GnRH system of the chameleon brain was studied at light microscopic and ultrastructural levels by use of an immunohistochemical technique with antibodies directed against salmon gonadotrophin-releasing hormone. Immunoreactive (IR) perikarya were found in the anterior midbrain tegmentum. At this level numerous IR cell bodies were detected around the fasciculus longitudinalis medialis (FLM). The more rostral neurons were observed dorsal to the FLM and progressively tended to be lateral to it along the midline. More caudally, they were found ventral to the FLM. At the electron microscope level, these cells were seen to contain large granular vesicles and to receive numerous synaptic inputs. A prominent pathway was traced from these cell bodies along the medulla oblongata to the spinal cord. A second IR pathway ascended rostrally to the habenular complex. No IR perikarya were located in the anterior brain including the olfactory bulbs.

gamma-Aminobutyric acid and 5-hydroxytryptamine interrelationship in the rat nucleus raphe dorsalis: combination of radioautographic and immunocytochemical techniques at light and electron microscopy levels.

Serotonin and gamma-aminobutyric acid (GABA) neurons in the nucleus raphe dorsalis were identified by immunocytochemistry using antibodies to 5-hydroxytryptamine or GABA. The pattern of the 5-hydroxytryptamine and GABA immunostaining presented similar features: 5-hydroxytryptamine or GABA immunoreactive somata were fusiform or ovoid (15-20 micron) and positive dendritic profiles were found either without any connection with other nerve elements or in contact with one or several terminals. In addition, some 5-hydroxytryptamine nerve endings were apposed to 5-hydroxytryptamine immunoreactive cell bodies or dendrites; also some GABA-immunopositive terminals were in contact with GABA-immunopositive nerve cell bodies. On the other hand, GABA and 5-hydroxytryptamine patterns may be differentiated in several respects: the 5-hydroxytryptamine-reactive nerve cell bodies were more numerous than the GABA ones. Some small, round (8-10 micron) nerve cell bodies were reactive with GABA antiserum, but no neurons of this type were reactive with a 5-hydroxytryptamine antiserum; finally, GABA nerve terminals were more numerous than 5-hydroxytryptamine ones. In order to understand the relationship between GABA and 5-hydroxytryptamine neurons, radioautographic and immunocytochemical procedures were combined: 5-hydroxytryptamine and GABA immunocytochemistry was combined with radioautography of [3H]GABA and [3H]5-hydroxytryptamine uptake, respectively. Some nerve cell bodies, dendrites or terminals, which were 5-hydroxytryptamine-immunopositive, were also capable of accumulating [3H]GABA and, conversely, some GABA-immunopositive elements were capable of accumulating [3H]5-hydroxytryptamine. Moreover, several nerve elements were reactive with both glutamate decarboxylase and 5-hydroxytryptamine antisera. These data confirm in electron microscopy previous studies suggesting the coexistence of both GABA and 5-hydroxytryptamine in the same neurons. The presence of uptake mechanisms for GABA and 5-hydroxytryptamine may indicate the action of both neurotransmitters in the same neuron. On the other hand, the [3H]GABA-labelled nerve endings in contact with 5-hydroxytryptamine-positive dendrites or nerve cell bodies indicate the possibility of a GABAergic control of the activity of some 5-hydroxytryptamine neurons; this corroborates biochemical and electrophysiological studies whereby a trans-synaptic control of the 5-hydroxytryptamine neurons by GABA may be envisaged.

Gamma-aminobutyric acid-immunoreactivity in the rat hippocampus. A light and electron microscopic study with anti-GABA antibodies.

The distribution of GABA-immunoreactive neurons and axonal varicosities was investigated in the hippocampal region of the rat brain by means of an indirect peroxidase immunocytochemical method with recently developed anti-GABA antibodies. The immunolabeling was found to be restricted to nervous structures: neuronal cell bodies, dendrites and axon terminals. Myelinated axons showing GABA-immunoreactivity were also observed. GABA-immunoreactive neurons were found in great number in the stratum pyramidale, the superficial part of the stratum oriens and the deep part of the stratum radiatum in the Ammon's horn. Less were found in the other regions; rare labeled cells were observed in the superficial part of the stratum radiatum and the middle part of the stratum oriens. The dentate gyrus exhibited numerous labeled cells in the granular layer, few in the hilus, rare in the molecular layer. A high density of GABA-immunoreactive terminals was found at the limit of the stratum oriens with the alveus, in the stratum pyramidale and in the stratum lacunosum. A lower density of labeled fibers was observed in the other areas. The somata and proximal dendrites of pyramidal and granular cells were encompassed by characteristic pericellular arrangements of GABA-immunoreactive varicosities. Ultrastructural observations revealed a diffuse immunoreaction product spread over the cytoplasm and the nucleus without specific relationship with the organelles, and immunoreactive aggregates in the cytoplasm. Labeled dendrites often showed enlargements displaying the immunoreaction whereas thinner segments were devoid of it. They received numerous asymmetrical synapses from unlabeled axon terminals. GABA-immunoreactive terminals were filled with small clear vesicles with immunopositive membranes and were observed in symmetrical contact with somata and dendrites.

Ultrastructural immunocytochemistry of gamma-aminobutyrate in the cerebral and cerebellar cortex of the rat.

gamma-Aminobutyrate containing structures in the cerebral and cerebellar cortex of the rat were visualized by an immunocytochemical method using glutaraldehyde fixation and an antiserum developed against a gamma-aminobutyrate-glutaraldehyde-protein conjugate. Labelled elements (perikarya and cell processes) were observed to be distributed throughout the layers of the cerebral cortex in a pattern similar to that described using glutamate decarboxylase immunocytochemistry. The morphological features of many immunoreactive cell bodies were typical of stellate neurons. In the cerebellar cortex, Purkinje, basket, Golgi and stellate, cell bodies were found to be immunoreactive along with numerous labelled neuronal processes. At the ultrastructural level, the labelled processes in both areas corresponded to immunoreactive dendrites and fibres. Labelled synaptic boutons, generally of the symmetrical type, could also be seen in contact with positive or negative cell bodies and dendrites. In the cerebellum, glomeruli could be clearly identified including mossy fibres surrounded by unlabelled dendrites in contact with immunoreactive terminals. At the subcellular level in both brain regions, the areas occupied by the Golgi apparatus were never labelled, although the nuclei had varied reactions. The strong glutaraldehyde fixation that limits the diffusion of gamma-aminobutyrate limits also antibody diffusion. However, this fixation is compatible with a good morphological preservation and should enable immunocytochemistry studies to be compared to other methods such as autoradiography.

Direct electron microscopic evidence for the coexistence of GABA uptake and endogenous serotonin in the same rat central neurons by coupled radioautographic and immunocytochemical procedures.

In order to detect on the same preparation of rat brain both 5-HT-containing elements and [3H]GABA uptake sites, immunocytochemistry (ICC) and radioautography (RAG) were combined in electron microscopy on sections of dorsal raphe nucleus (DRN) involving supraependymal fibers (SEF). At the ultrastructural level, SEF and DRN dendritic processes could be ICC positive and RAG negative, ICC positive and RAG positive, ICC negative and RAG positive, or negative for both labelings. Because of technical limitations a negative reaction should be interpreted with caution. However, the results constitute another morphological basis for intracellular relationship of endogenous 5-HT and exogenous GABA and provide additional evidence for the possible bipotentiality of some neuronal elements for both transmitters.

A radioautographic and immunocytochemical study of the GABA systems of the habenula complex in the rat.

Radioautography of [(3)H]GABA accumulation and immunocytochemistry of glutamate decarboxylase have been used to study anatomically and morphologically the GABA system of the rat habenular (Hb) complex. Radioautographic visualisation of GABA specific neurons show a very high innervation of the complex including both stria medullaris (SM), the habenular commissure and the periventricular thalamic fibers (FPVT). A massive labeled fiber system in the SM appears to divide into two branches when it reaches the Hb nuclei: a part of fibers continue their course dorsally to the nuclei up to the habenular commissure; other fibers enter the Hb lateralis or run along the ventral Hb medialis at the level of FPVT. The staining is markedly diminished in the entire complex in response to SM lesions. In the Hb lateralis, the radioautographic-positive reaction is mainly bound to labeled fibers or axonal varicosities. However GAD immunocytochemistry reveals some GAD-positive cell bodies in the ventro-median portion of the nucleus. In the Hb medialis the radioautographic and immunocytochemical staining is observed in the neuropile between the unlabeled large cell bodies. In the subependymal layer bundles of processes are strongly labeled and form a continual strain behind the unlabeled ependymocytes. Three types of reactive terminals have been differentiated based on size and shape of vesicles. Some of them are exclusively characterized by clear round vesicles and probably have their origin in the septum. Others contain clear vesicles and some large dense-cored vesicles and disappear after mesencephalic Raphe lesions or 5,7-dihydroxytryptamine treatment. They could correspond to terminals of raphe neurons with a double potentiality GABA and 5HT. The last exhibit mainly a dense population of large dark-cored granules similar to the ones found in neurosecretory nerve endings. However numerous fibers morphologically similar to the reactive fibers are unlabeled.

Radioautographic evidence for an innervation of the subcommissural organ by GABA-containing nerve fibres.

Light-and electron-microscopic radioautographic studies were carried out in rats after intraventricular injection of [3H]GABAergic elements in the subcommissural organ (SCO). This amino acid is specifically accumulated in SCO ependymocytes and numerous nerve terminals and fibres. Some labelled terminals contain clear round vesicles and large granular vesicles and sometimes display synaptic contacts on the SCO ependymocytes. They disappear after 5,7-dihydroxytryptamine (5,7-DHT) treatment or lesions of mesencephalic raphé nuclei. They are morphologically and pharmacologically similar to the serotonin-containing terminals of the basal SCO. The other labelled terminals contain exclusively clear round vesicles, are dispersed throughout the SCO and survive after the 5,7-DHT treatment or raphé nuclei lesions; some of them are in synaptic contact with neuronal elements of the basal SCO. In both SCO ependymocytes and fibres or terminals, [3H]GABA is accumulated according to the pharmacological criteria of a GABA neuronal uptake. Under the same experimental conditions [3H[glutamine and beta[3H]alanine fail to label the SCO: [3H] glutamate produces a very light labelling and [3H] serotonin is accumulated only in nerve profiles of the basal SCO. These results, and the presence of a glutamate decarboxylase activity in the SCO, suggest the existence of GABA-synthesizing elements in the SCO and could indicate the possible involvement of GABA in the secretory activity of the SCO.