Manganese tissue accumulation and tyrosine hydroxylase immunostaining response in the Neotropical freshwater crab, Dilocarcinus pagei, exposed to manganese.

Manganese (Mn) is an essential metal for the development and function of the mammalian brain; however, excess Mn accumulation may cause neurological abnormalities resembling Parkinson's disease due to reductions in brain dopamine levels. Because dopamine also regulates many functions in crustaceans, this study examined the effects of Mn accumulation in Dilocarcinus pagei, a Neotropical freshwater crab. Following a 72-h exposure to graded concentrations of MnCl2, Mn accumulation was assessed in several tissues. Glycaemia and the tyrosine hydroxylase (TH) immunostaining response were also examined as indicators of catecholaminergic function and catecholaminergic cell integrity, respectively. Tissue Mn accumulation was variable and occurred in the following order: gills > hepatopancreas > claw muscle > haemolymph. Exposure to 2 mM Mn reduced the gill levels of calcium, copper and iron, whereas Mn at all concentrations decreased zinc levels. All Mn-exposed animals showed lower copper levels in the hepatopancreas and haemolymph. Exposure to 2.0 mM Mn increased the haemolymph calcium. Mn exposure had no effect on glycaemia, whereas exposure to low Mn concentrations reduced the TH immunostaining response. Analysis of the central nervous system revealed the greatest Mn effect in the cerebral ganglion and the least effect in the abdominal ganglia. These results suggest the operation of an adaptive mechanism for tissue accumulation that could be responsible for the lack of an association between Mn concentrations and metal accumulation. The findings also suggest that Mn, calcium, iron and zinc share a transporter in gill cells and that Mn resistance is greater in the TH-positive cells of this crustacean than in mammalian cells.

Tyrosine hydroxylase protein expression in ventral nerve cord of Neotropical freshwater crab.

Given the importance of catecholamines in coordinating physiological and behavioral responses in brachyurans, the present study was designed to investigate the distribution of tyrosine hydroxylase (TH)-positive cells and fibers in the ventral nerve cord of Dilocarcinus pagei the Neotropical freshwater crab. TH immunoreactivity was visualized in adult crabs of both sexes, during the intermolt period. We found TH-positive cells that have not been previously described in brachyurans. Specifically, we found a pair of TH-positive cells in the ventral region of the thoracic ganglion, and in ventral and dorsal regions of the abdominal (pleonic) ganglion, suggesting catecholaminergic modulation of claws' function and abdominal structures. In addition, great population of TH-positive cells was observed in the subesophageal ganglion, indicating conservation during evolution of catecholamines in this ganglion of decapods. Dopamine is present in cells and fiber tracts of brachyuran ventral nerve cord, projecting to endocrine, cardiac and digestive structures, suggesting widespread modulation and control of physiological functions and behavior. Dopamine plays a central role in movement and psychiatric disorders in humans. Information on dopaminergic function in the nervous system of invertebrates should improve the understanding of its function in more complex systems, such as human beings.

Manganese homeostasis and transport.

The review addresses issues pertinent to Mn accumulation and its mechanisms of transport, its neurotoxicity and mechanisms of neurodegeneration. The role of mitochondria and glia in this process is emphasized. We also discuss gene x environment interactions, focusing on the interplay between genes linked to Parkinson's disease (PD) and sensitivity to Mn.

Macrophages-mediated neurotoxic effects of intra-nigral manganese administration are attenuated by minocycline.

The present study was designed to address the role of macrophages in Mn-induced neurotoxicity and to test the hypothesis that minocycline, a tetracycline derivative, attenuates the biochemical and morphological sequelae of Mn. Mn was unilaterally microinjected into rat nigra followed by systemic minocycline or saline administration 24h later, daily for 3 days. At 72h after the intranigral Mn microinjection, tyrosine hydroxylase immunostaining (TH-IS) was evaluated in the striatum, along with the number of macrophages (as indicated by CD11b immunostaining) in the substantia nigra. Mn significantly reduced striatal TH-IS, and causes an increased macrophage number at the lesion site when compared with the control group. The effects of Mn on striatal TH-IS and the number of macrophages at the lesion site were concentration dependent. Consistent with the stated hypothesis, minocycline significantly reduced the macrophage number in the lesion site and minimized the TH-IS striatal loss induced by Mn. These results indicate that an inflammatory response mediated by macrophages is induced by intranigral Mn microinjection, which is fully attenuated by minocycline treatment, suggesting that suppression of macrophage infiltration provides neuroprotection to dopaminergic neurons.

Manganese neurotoxic time course is not influenced by L-deprenyl systemic treatment: influence of L-deprenyl in manganese neurotoxic time course.

Unilateral microinjection of manganese into the rat substantia nigra pars compacta (SNpc) leads to the death of nigral neurons and a decrease in dopamine (DA) within the ipsilateral striatum. L-deprenyl, an irreversible inhibitor of monoamine oxidase B, appears to protect or rescue dopaminergic nigral neurons from the toxic effects of 6-hydroxydopamine (6-OHDA) and 1-methyl-4 phenyl-1, 2, 3, 6-tetrahydropiridine (MPTP). In this study we aimed to investigate whether L-deprenyl is able to influence the manganese neurotoxic time course. L-deprenyl rescue activity was evaluated in discontinuous posology and its protective effect was evaluated in a continuous one. Apomorphine-induced rotational behavior and striatal tyrosine hydroxylase immunostaining (TH-IS) were evaluated in both conditions at 24 h, 72 h and 168 h after intranigral microinjections. Our results indicate a failure in L-deprenyl to influence the establishment and time course of rotational response to apomorphine. Strikingly, a further decrease in the tyrosine hydroxylase immunostaining, at 168 h post microinjection in L-deprenyl-treated rats was obtained. Our data revealed no correlation between an increasing rotational behavior and reduction in TH-IS.

Clearance of manganese from the rat substantia nigra following intra-nigral microinjections.

Chronic exposure to manganese (Mn) positively correlates with the occurrence of Parkinsonism but little is known about mechanisms of its neurotoxicity. In the present study, we determined the clearance of Mn from rat substantia nigra after its nigral injection and correlated it with the establishment of apomorphine-induced rotational behaviour and loss of striatal tyrosine hydroxylase (TH) immunoreactivity. Our results suggest that Mn is slowly cleared from the substantia nigra, following a first-order kinetics with a t(1/2) of 3 days. Appearance of apomorphine-induced rotational behaviour and loss of TH immunoreactivity within the striatum follows metal clearance were both detected 24 hours after intra-nigral Mn microinjection and maximal 72 hours after injection. The present data suggest that the cellular mechanisms induced by Mn and leading to dopaminergic cell death, occurred shortly after its injection and that the metal concentration needs to reach a threshold value to induce neurotoxic effects. This would indicate that nigral damages are a direct consequence of Mn accumulation.

Neurobiologia do parkinsonismo: I. Substratos neurais e neuroquímica dos gânglios basais / Neurobiology of parkinsonism: I. Neural substrates and neurochemistry of the basal ganglia

As desordens do movimento caracterizam-se pelo rompimento da harmonia existente entre os múltiplos sistemas cerebrais e musculares responsáveis pela integraçäo do indivíduo com o seu meio e espécie. Dentre os sistemas cerebrais, os gânglios basais säo a sede das manifestaçöes motoras presentes tanto nas hipercinesias quanto nas hipocinesias. A busca de agentes etiológicos para o parkinsonismo em muito tem contribuido para o conhecimento da organizaçäo neuroanatômica dos gânglios basais, sugerindo a existência de múltiplos sub-sistemas dentro do circuito córtex-gânglios da base-tálamo-córtex. Nesta revisäo a existência de múltiplos sub-sistemas dentro do circuito córtex-tálamo-córtex. Nesta revisäo apresentamos os principais sistemas e sub-sistemas envolvidos no parkinsonismo

Neurobiologia do parkinsonismo: II. Modelos experimentais / Neurobiology of parkinsonism: II. Experimental models

O emprego de moedelos experimentais de parkinsonismo tem contribuído näo só para explicar o conhecimento das funçöes dos gânglios basais como também tem permitido o surgimento de várias hipótesis para explicar os processos neurodegenerativos do sistema nervoso central. Nesta revisäo säo apresentados e discutidos os modelos de parkinsonismo que utilizam neurotoxinas como a 6-hidroxidopamina, MPTP e o manganês