Halima Gamrani

Chronic lead intoxication affects glial and neural systems and induces hypoactivity in adult rat

Lead is an environmental toxin and its effects are principally manifested in the brain. Glial and neuronal changes have been described during development following chronic or acute lead intoxication, however, little is known about the effects of chronic lead intoxication in adults. In this study we evaluated immunohistochemically the glial and dopaminergic systems in adult male Wistar rats. 0.5% (v/v) lead acetate in drinking water was administrated chronically over a 3-month period. Hypertrophic immunoreactive astrocytes were observed in the frontal cortex and other brain structures of the treated animals. Analysis of the astroglial features showed increased number of astrocyte cell bodies and processes in treated rats, an increase confirmed by Western blot. Particular distribution of glial fibrillary acidic protein immunoreactivity was observed within the blood vessel walls in which dense immunoreactive glial processes emanate from astrocytes. Glial changes in the frontal cortex were concomitant with reduced tyrosine hydroxylase immunoreactive neuronal processes, which seem to occur as a consequence of significantly reduced dopaminergic neurons within the nucleus of origin in the substantia nigra. These glial and neuronal changes following lead intoxication may affect animal behavior as evidenced by reduced locomotor activity in an open field test. These findings demonstrate that chronic lead exposure induces astroglial changes, which may compromise neuronal function and consequently animal behavior.

Aluminum affects glial system and behavior of rats

Aluminum (Al) has been associated with neuronal dysfunction. These neuronal changes may involve glial alterations. We intend to evaluate the consequence of Al on the glial system and the behavior of rats exposed chronically to 0.3% of aluminum chloride in drinking water during 4 months in adulthood (A) or since intra-uterine age (IU); animals from this latter group were sacrificed at four months of age. Our data show an intense glial fibrillary acidic protein (GFAP)-immunoreactivity with a high density of astrocytes in both treated groups compared with controls. However, in IU rats, astrocytes display prominent glial cell bodies and processes. A and IU rat groups perform a significantly reduced locomotor activity. However, using the dark/light box test, the IU rats prefer to spend more time in the enlightened compartment compared to other groups. Behavioral and glial changes caused by Al exposure bring support for the role of Al in brain dysfunction involving glial alterations.

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.

Effects of chronic lead intoxication on rat serotoninergic system and anxiety behavior.

Chronic lead exposure has been shown to produce behavioral disturbances in human and animal models. These disturbances are associated with alterations in monoaminergic neurotransmission in the central nervous system (CNS), some of which have been attributed to serotonin (5-HT). This study was undertaken to investigate the chronic effects of lead exposure on the serotoninergic system in the dorsal raphe nucleus (DRN) and the consequences of its toxicity on rat behavior. Adult male Wistar rats were chronically exposed for 3 months to 0.5% lead acetate in drinking water. The serotoninergic system was evaluated using immunohistochemistry and the anxiety behavior was assessed by the light/dark box test. The results show that chronic lead exposure induces a significant increase of blood and brain lead levels in treated rats compared with controls. The density of the immunoreactive serotoninergic cell bodies was significantly higher in treated rats in all parts of the DRN. Assessment of animal behavior using the light/dark box test showed that lead-treated rats spent significantly more time in the light chamber compared with controls (P=0.001). These findings suggest that lead exposure may possibly induce increased anxiety as a consequence of changes in neuronal 5-HT content in the DRN.

Water deprivation affects serotoninergic system and glycoprotein secretion in the sub-commissural organ of a desert rodent Meriones shawi

Water deprivation is a stress that has been associated with activation of several endocrine systems, including circumventricular organs of the central nervous system. The sub-comissural organ (SCO), characterized by its glycoprotein secretion called Reissners fiber has been suggested to play a role in the regulation of body water balance. Meriones shawi, a semi-desertic rodent characterized by its resistance to long periods of thirst was subjected to water deprivation for 1 and 3 months. Effect of water deprivation was evaluated immunohistochemically on 5-hydroxytryptamine (5-HT; serotonin) system and glycoprotein secretion of the SCO. Our findings demonstrate significant reduction of anti-Reissners fiber immunoreactive materials within basal and apical parts of the SCO ependymocytes. These changes seem to be the consequence of reduced control by 5-HT fibers reaching the SCO as a concomitant and significant reduction of anti-5-HT immunoreactive fibers are also observed following water deprivation. 5-HT immunoreactive reduction is seen in several regions in the brain including the neurons of origin within the dorsal raphe nucleus and the projecting supra and sub-ependymal fibers reaching the classical ependyma of the third ventricle. The extent of Reissners fiber and 5-HT immunoreactive changes significantly correlates with the severity of water restriction. We suggest that water deprivation causes changes of the classical ependyma and the specialized ependyma that differentiates into the SCO as well as other cirumventricular organs such as the subfornical organ and the organum vasculosum laminae terminalis known to control drinking behaviors.

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 Reissners 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 Reissners 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.

Chronic exposure to aluminum reduces tyrosine hydroxylase expression in the substantia nigra and locomotor performance in rats.

Aluminum (Al) is a neurotoxic agent that accumulates in the substantia nigra of patients affected by Parkinsons disease and in other cerebral areas of different neurodegenerative pathologies. Al has been associated with neuronal and glial dysfunctions, and neuronal changes have been suggested to affect several neurotransmitter systems including the dopaminergic system. The present study was designed to evaluate by means of immunohistochemistry using antibodies against tyrosine hydroxylase (TH; the rate-limiting enzyme of dopamine synthesis) the effects of chronic Al exposure (0, 3%) in drinking water during 4 months in adulthood or since intra-uterine age in the substantia nigra. Our results show a significant decrease in the number of cells labeled by the antibody against TH in rats treated with Al compared to controls. The TH-immunoreactive decrease following Al treatment is accentuated in the rat group treated since intrauterine age. In both treated groups, Al exposure induced a significant decrease of locomotor performance. Interestingly, as for TH-immunoreactivity, the decreased locomotor activity was also accentuated in the group treated since intrauterine age. The Al-induced TH alterations may be one of the causes of aluminum-induced neurotoxicity.

Effects of chronic and acute lead treatments on the biophysical properties of erythrocyte membranes, and a comparison with model membranes

Rat erythrocytes, or erythrocyte membrane ghosts, have been subjected to either chronic (drinking water containing 15 mM lead acetate for 3 months) or acute (10−9–10−2 M lead acetate for 1 h) Pb2+ treatments and subsequent changes in membrane properties have been measured. Pb2+ concentration in chronically treated rat plasma was 1.8 μM, which is one order of magnitude above normal values. Membrane permeability, or hemolysis, was increased in both cases. A comparative study using liposomes, in the form of large unilamellar vesicles, also indicated an increase in membrane permeability. Membrane microviscosity, or acyl chain molecular order, measured as DPH fluorescence polarization, showed an increased order in the acute treatments, at least below 700 μM Pb2+, and a similar increase in chronically treated rats. The correlation between acute and chronic treatments, and between cell and model membranes, suggests that the present observations may be relevant in the pathogenesis of lead intoxication in humans.

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.

Differential patterns of glial fibrillary acidic protein-immunolabeling in the brain of adult lizards.

The present study describes by means of immunohistochemistry the comparative distribution of glial fibrillary acidic protein (GFAP)‐positive cells in the forebrain and midbrain of three species of lizards: Eumeces algeriensis, Scincoidae; Agama impalearis, Agamidae; Tarentola mauritanica, Gekkonidae. In the species studied, the different types and proportions of glial cells expressing GFAP showed considerable variation. These cells include radial glia, oval cells, tanycytes, ependymocytes, glia limitans, and astrocytes. In Eumeces, astrocytes are particularly abundant and their processes form numerous perivascular end‐feet; in addition well‐differentiated ependymal cells and glia limitans express GFAP. These mature glial features are concordant with the relatively advanced phylogenetic level of Eumeces. In Tarentola, relatively few GFAP‐expressing glial cells are observed, consisting mainly of radial glia and tanycytes. These features indicate a relatively immature state of the glial cell populations in this species. In Agama, GFAP‐immunostained cells are confined to the periventricular and subpial brain areas; the ventricular lining contains numerous GFAP‐immunopositive tanycytes and well‐differentiated glia limitans. This pattern indicates that the glial cell profile in Agama exhibits characteristics intermediate between Eumeces and Tarentola, a feature which is discordant with the relatively primitive phylogenetic level of Agamidae compared to Gekkonidae. Together, the results of the present study provide novel data on the characterization of GFAP‐expressing cell populations in different species of lizards. We suggest that the different glial patterns observed in the lizard brain correlates with developmental and functional aspects. J. Comp. Neurol. 464:159–171, 2003.