Omar El Hiba

A blunted anxiolytic like effect of curcumin against acute lead induced anxiety in rat: involvement of serotonin.

Anxiety is one of the most common mental disorders sharing extreme or pathological anxiety states as the primary disturbance in mood or emotional tone, with increased fear and exaggerated acute stress responses. Medicinal plants are very variable, but some of them are used as a spice such as curcumin (Curcuma longa). Curcumin shows a wide range of pharmacological potentialities, however, little is known about its anxiolytic properties. The aim of our study was to assess the anti-anxiety potential of curcumin extract against experimental lead induced-anxiety in rats. Experiments were carried out on male Wistar rats intoxicated acutely with an intraperitoneal injection of Pb (25mg/kg B.W.) and/or concomitantly with administration of curcumin (30 mg/kg B.W.) for 3 days. Using immunohistochemistry and anxiety assessment tests (dark light box and elevated plus maze), we evaluated, respectively, the expression of serotonin (5HT) in the dorsal raphe nucleus (DRN) and the anxiety state in our animals. Our results showed, for the first time, a noticeable anxiolytic effect of curcumin against lead induced anxiety in rats and this may possibly result from modulation of central neuronal monoaminergic neurotransmission, especially serotonin, which has shown a significant reduction of the immunoreactivity within the DRN.

Cellular plasticity in the supraoptic and paraventricular nuclei after prolonged dehydration in the desert rodent Meriones shawi: Vasopressin and GFAP immunohistochemical study.

Supraoptic (SON) and paraventricular (PVN) nuclei are part of the hypothalamic-neurohypophysial system, they constitute the main source for vasopressin and they represent also obvious examples of activity-dependent neuroglial plasticity. Certain physiological conditions such as dehydration are accompanied by a structural remodeling of the neurons, their synaptic inputs and their surrounding glia. In the present work, an adult Meriones shawi (a rodent adapted to desert life) is used as an animal model. Using GFAP and vasopressin expressions as indicators successively of astrocytes and neuronal activations, the effect of a prolonged episode of water deprivation on the SON and PVN, hypothalamus nuclei were examined. We studied the immunoreactivity of GFAP and vasopressin in various hydration states (total deprivation of drinking water for 1 and 2months compared to hydrated animals). Prolonged dehydration produces an important decrease of GFAP immunoreactivity in both SON and PVN after 1 and 2months of water restriction. This decrease is accompanied by increased vasopressin immunoreactivity following the same periods of water deprivation. These findings may explain a real communication between vasopressin neurons and their surrounding astrocytes, thus the retraction of astrocytes and their processes is accompanied by an enhancement of vasopressin neuron density and their projecting fibers in response to this osmotic stress situation. Furthermore, these data could open further investigations concerning the possible involvement of the communication between astrocytes and vasopressin neurons in both PVN and SON in the regulation of Meriones hydrous balance and resistance to dehydration.

Behavioral, histopathological and biochemical impairments observed in mice envenomed by the scorpion: Hottentota gentili (Pallary, 1924).

Hottentota gentili is a black scorpion which has been considered as dangerous specie by many authors. However there are no data regarding minimal lethal dose and effects of the scorpion venom till now. We therefore aimed, by the present investigation, to assess on the one hand, the LD50 of H. gentili venom by sublethal injection and the effects on some vital organs, by a histological and a biochemical tools. On the other hand, the possible neurobehavioral impairments, in Swiss mice, 3 h, 6 h and 12 h following envenomation. The LD50 of H. gentili scorpion venom was found to be 0.46 mg/kg by subcutaneous injection route. Venom produced focal fragmentation of myocardial fibers, while lungs showed rupture of the alveolar structure. Intestines showed selective histopathological changes. Concomitantly, there was a significant rise in the serum enzymes levels, as well as hyperkalemia and a high level of plasma albumine and creatine. Proteinuria was also observed. The observed behavioral effects were a hypoactivity in the both experiments 30 min and 3 h after injection. The envenomation produced an increased immobility time only 30 min and 3 h post injection in the tail suspension test (TST).

Pathophysiological and neurobehavioral injuries in mice experimentally envenomed with Androctonus liouvillei (Pallary, 1928) scorpion venom.

The genus Androctonus is represented by 7 scorpion species in Morocco. All studies conducted on the characterization of Androctonus species venom are limited to Androctonus mauritanicus. However, there is other species which arouses also interest of scientists due to their high toxicity. Thus, we chose to assess the toxic effect of Androctonus liouvillei venom by sublethal injection and the effects on some vital organs, by a histological and a biochemical tools. In addition, we aimed to characterize the neurobehavioral impairments, in Swiss mice, 3h, 6h and 12h following envenomation. The LD50 of A. liouvillei scorpion venom was found to be 0.29mg/kg by subcutaneous injection route. Venom administration induced glomerular destruction and disorganization in the Bowmans spac. Examination of lungs showed a remarkable focal rupture of the alveolar structure and intra-alveolar hemorrhage. Concurrently, there was a significant enhancement in the serum enzymes levels of AST, ALT, CPK and LDH, and a high level of glucose and creatinine. Proteinuria was also observed. Regarding the behavioral effects we noted a hypoactivity and anxiogenic-like effect, manifested by an increased time spent in the open arms in groups tested 30min and 12h after the injection. Concomitantly with an increased immobility time in the tail suspension test. The present finding show an obvious profound neuromodulatory effect of A. liouvillei venom manifested by an impaired neurobehavioral and physiological patterns in mice that may in part explain the toxic effect of the venom in human as one of the potent death agents.

Increased Reissner's fiber material in the subcommissural organ and ventricular area in bile duct ligated rats

Hepatic encephalopathy is a common neuropsychiatric complication of acute and chronic liver failure. Whether brain structures with strategic positions in the interface of blood-brain barriers such as the circumventricular organs are involved in hepatic encephalopathy is not yet established. Among the circumventricular organs, the subcommissural organ secretes a glycoprotein known as Reissners fiber, which condenses and forms an ever-growing thread-like structure into the cerebrospinal fluid. In the present work we describe the Reissners fiber material within the subcommissural organ and its serotoninergic innervation in an animal model of chronic hepatic encephalopathy following bile duct ligation in experimental rats. The study involved immunohistochemical techniques with antibodies against Reissners fiber and 5-hydroxytryptamine (5-HT). Four weeks after surgical bile duct ligation, a significant rise of Reissners fiber immunoreactivity was observed in all subcommissural organ areas compared with controls. Moreover, significant Reissners fiber immunoreactive materials within the ependyma and inside the parenchyma close to the ventricular borders were also seen in bile duct ligated rats, but not in control rats. Increased Reissners fiber material in bile duct ligated rats seems to be related to a reduction of 5-HT innervation of the subcommissural organ, the ventricular borders and the nucleus of origin, the dorsal raphe nucleus. Our data describe alterations of the subcommissural organ/Reissners fiber material and the subcommissural organ 5-HT innervation probably due to a general 5-HT deficit in bile duct ligated rats.

Loss of tyrosine hydroxylase expression within the nigro-striato-cortical pathways in the cirrhotic rat: the possible restorative effect of the neurosteroid dehydroepiandrosterone sulfate.

Hepatic encephalopathy (HE) is a neuropsychiatric disorder occurring as a consequence of both acute and chronic liver failure. Advanced HE is generally accompanied with extrapyramidal symptoms including rigidity and tremor, which may reflect alterations of the dopaminergic system. Recently we reported a beneficial effect of the neuroactive steroid dehydroepiandrosterone sulfate (DHEAS) in cirrhotic rats, however the mechanisms of such an effect by DHEAS were not addressed. In the present study, we describe the changes of the dopaminergic system occurring in the cirrhotic rats and concomitantly we investigated the effect of DHEAS on this system in Sprague-Dawley rats using the expression of tyrosine hydroxylase (TH) as a neuronal marker. Rats were submitted to bile duct ligation (BDL) surgery and TH immunohistochemistry was assessed in the Substantia nigra pars compacta (SNc), striatum, ventral tegmental area (VTA) and the cortex. TH immunoreactivity showed a significant diminution in both SNc and VTA concomitantly with the cortical and the striatal outputs in the BDL rats vs. controls. Three daily injections of 5mg/kg of DHEAS to BDL rats significantly normalized TH expression decrease in both SNc and VTA as well as dopaminergic projections to the striatum and the cortex of BDL rats. The present data support an involvement of the dopaminergic system in mild HE and a possible beneficial effect of the neurosteroid DHEAS as a potential pharmacological treatment of mild HE.

The rat SCO responsiveness to prolonged water deprivation: implication of Reissner's fiber and serotonin system.

The osmotic stress is a potent stimulus that can trigger several peripheral as well as central impairments. The brain is a vulnerable target of the osmotic stress and particularly circumventricular organs (CVOs) regarding their strategic localization as sensory organs of biochemical changes in the blood and cerebrospinal fluid circulations. The subcommissural organ (SCO) is a CVO which releases doubly in the CSF and blood circulation a glycoprotein called Reissners fiber (RF) that has been associated to several functions including electrolyte and water balances. The present work was aimed on the assessment of the secretory activity of the SCO and its serotoninergic innervation following 2 weeks of total water restriction in Wistar rat. Using the immunohistochemistry of RF and serotonin (5HT), our data showed a significant overall reduction of RF immunoreactivity within both ependymal and hypendymal cells of the SCO of dehydrated rats compared to their corresponding controls, this decrease was concomitant with an enhancement of fibers 5HT immunoreactivity in the SCO as well as in the classical ependyma and in the dorsal raphe nucleus (DRN), constituting the origin of this innervation. The present findings support the possible involvement of the SCO in the response to prolonged water deprivation by decreasing its secretory materials which may result from either a direct peripheral hormonal control and/or the consequence of the enhanced 5HT innervation of the SCO.

Differential regional responsiveness of astroglia in mild hepatic encephalopathy: An Immunohistochemical approach in bile duct ligated rat

Hepatic encephalopathy (HE) is a neuropsychiatric disorder that occurs in both acute and chronic liver failure. However, the pathomechanisms of the disease remains obscure. Neuropathological studies have demonstrated a primary gliopathy in humans as well as in animal models of chronic and acute liver failure. Here, we have investigated in an animal model of mild HE: the bile duct ligated rat (BDL) at the cirrhotic stage (4 weeks after surgery), the expression of the key marker of mature astrocytes; the glial fibrillary acidic protein (GFAP) in different brain areas such as: Substantia nigra pars compacta (SNc), Ventral tegmental area (VTA), hippocampus, dorsal striatum and brain cortex by means of immunohistochemistry. The immunohistochemical study showed, in BDL compared to the operated controls (shams), a diminished astrocyte reactivity corresponding to a loss of GFAP expression within SNc, VTA, hippocampus and dorsal striatum (p<0.05),whereas in the brain cortex astrocytes appeared strongly immunoreactive with increased GFAP expression (p<0.05) as compared to shams. Our finding demonstrated differential astroglial responses which depend to the specificity of the area investigated and its particular neuronal neighboring environment, and could have possible outcomes on the diverse neuronal functions especially those observed during the different episodes of hepatic encephalopathy.

Structural and neurochemical plasticity in both supraoptic and paraventricular nuclei of hypothalamus of a desert rodent Meriones shawi after a severe dehydration versus opposite treatment by rehydration: GFAP and vasopressin immunohistochemical study.

Various lines of evidence indicate that astrocytes can undergo morphological changes that modify their relationship to adjacent neurons in response to physiological stimulation such as dehydration. Supraoptic (SON) and paraventricular (PVN) nuclei of hypothalamus represent obvious examples of activity-dependent neuro-astrocytic plasticity. In the present study, Meriones shawi is used as an animal model. Moreover, GFAP and vasopressin expressions are used as indicators successively of astrocytes and neuronal activations. In order to evaluate the reversibility of the neuro-astrocytic plasticity in SON and PVN, prolonged episode of water deprivation followed by episode of rehydration were examined. Hence, we studied the immunoreactivity in various hydration states: water ad libitum, dehydration, and rehydration of animals. Our results showed that dehydration of Meriones induced a significant decrease of GFAP immunoreactivity accompanied by a significant increase of AVP immunoreactivity, the latter concerns both cell bodies and fibers in the same hypothalamic nuclei SON and PVN. Conversely, rehydration of animals shows a reversible phenomenon leading a return of vasopressin and GFAP immunoreactivities to the control level. These results show that both astrocytes and vasopressin neurons display a remarkable structural and physiological plasticity, allowing to M. shawi, a great ability to support the hostile conditions in dry environment.

Alteration of dopaminergic innervation and voluntary movements after long period of thirst in a semi-desert rodent, Meriones shawi : Behavioral and immunohistochemical studies

Dehydration is a powerful stimulus causing disequilibrium in homeostasis of water and electrolytes resulting from depletion in total body water. Most studies have focused on domestic and laboratory animals; however, the study of desert animals allows improved understanding about water balance and resistance to dehydration and associated behavioral changes, including those related to voluntary movements. Meriones shawi (Shaws Jird) is a desert rodent characterized by its resistance to long periods of thirst that can extend for several months. In the present study, M. shawi were subjected to water deprivation for 1month. We used tyrosine hydroxylase immunohistochemistry (TH: the key enzyme of catecholamine biosynthesis) to evaluate the effects of prolonged dehydration on the dopaminergic system in both substancia nigra pars compacta and ventral tegmental area (SNpc and VTA), which are the main sources of dopamine input to several brain areas; the immunolabelling was performed also in both the medial forebrain bundle and the caudate putamen (striatum). In addition, the open-field test was used to evaluate the effect of dehydration on locomotor activity in M. shawi. The results showed an increase in TH immunolabelling in both SNpc and VTA following 1month of dehydration compared to control levels. The same results were obtained with fibers in both MFB and striatum. This augmentation of TH immunoreactivity was accompanied by noticeable changes in locomotor activity behavior of Meriones, the recording test shows the hyperactivity of animals which is probably caused by dehydration. Overall, the results indicate that dehydration is able to increase dopaminergic neurotransmission, which might be involved in generating hyperactivity in this desert animal.