cDNA gene expression profile of rat hippocampus after chronic treatment with antidepressant drugs.

BACKGROUND: Chronic antidepressant treatment causes alterations in several hippocampal genes, which participate in neuronal plasticity. However the full picture of their mechanism of action is not known. The advent of genomics enables to identify a broader mechanism of action and identify novel targets for antidepressant development. METHODS: The present study examined the cDNA microarray gene expression profile in the hippocampus induced by chronic antidepressant treatment, in rats exposed to the forced swim test. Animals were treated for 2 weeks with moclobemide, clorgyline and amitriptyline. RESULTS: The three antidepressants significantly reduced immobility in the forced swim test and initiated significant homologous changes in gene expressions. These include up regulation of cAMP response element binding protein and down regulation of corticotrophin releasing hormone. Other gene changes noted were those related to neuropeptides, neurogenesis and synaptogenesis, including synaptophysin and neogenin. Some 89 genes were changed by at least 2 drugs, out of which 53 were changed oppositely by forced swim test. Confirmation of gene changes, have come from real time RT-PCR. CONCLUSIONS: A significant number and homology in gene expression were observed with the three antidepressants. Many of the genes were associated with neurogenesis and synaptogenesis, including synaptophysin and neogenin.

Oxidative stress indices in Parkinson's disease : biochemical determination.

ABSTRUCT: Parkinson's disease (PD) is associated with progressive degeneration of melanin-containing dopamine neuron cell bodies arising in the substantia nigra pars compacta (SNpc) and projecting terminals to the striatum. The disease is best characterized biochemically as a deficiency of striatal dopamine. The mechanism of neurodegeneration remains an enigma despite a large body of investigation and several hypotheses (1-5). In the past decade much has been learned about the chemical pathology of the disease. This progress has been helped by elucidation of the mechanism of the neurotoxic actions of 6-hydroxydopamine (6-OHDA) and N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which are used to induce animal models of this disease. Thus, the most valid current hypothesis concerning the pathogenesis of idiopathic PD is progressive oxidative stress (OS), which can generate excessive reactive oxygen species (ROS) selectively in the SNpc (1-9), and subsequent biochemical abnormalities (Table 1). In addition, the ROS scavenging system may also diminish, which would exaggerate the condition leading to accumulation of ROS. In PD, it is thought that both these events occur; Table 1 gives a summary of the biochemical changes identified to date in the SNpc of PD patients. Iron, monoamine oxidase B (MAO-B), copper/zinc superoxide dismutase (Cu/Zn-SOD), and heme oxygenase (radical producing) are increased; reduced glutathione (GSH) and vitamin C (radical scavenging) are decreased. Whether OS is a primary or secondary event in PD has not been established, but when it does occur, OS can lead to a cascade of events resulting in the demise of the nigrostriatal dopaminergic neurons. One approach toward protection of such neurons is the use of radical scavengers or iron chelators as neuroprotective drugs (10). Table 1 Biochemical Alterations in Substantia Nigra of Parkinson's Disease Indicating Oxidative Stress Elevated Decreased Iron (in microglia, astrocytes, oligodendrocytes, and melanized dopamine neurons and mitochondria) GSH (GSSG unchanged); GSH/GSSG ratio decreased Mitochondrial complex I Ferritin Calcium binding protein (calbindin 28) Mitochondrial monoamine oxidase B Transferrin and transferrin receptor Lipofuscin Vitamins E and C Ubiquitin Copper Cu/Zn-superoxide dismutase Cytotoxic cytokines (TNF-a, IL-1, IL-6) Inflammatory transcription factor NFKB Heme oxygenase-1 Ratio of oxidized to reduced glutathione (GSSG/GSH) Nitric oxide Neuromelanin.

Effect of cigarette smoke on salivary proteins and enzyme activities.

Exposure of human plasma in vitro to gas-phase cigarette smoke (CS) causes a marked modification of plasma proteins as measured by protein carbonyl assay. Aldehydes present in CS may cause this elevation of protein carbonyls by reacting with sulfhydryl groups of proteins. Saliva is the first body fluid to confront the inhaled CS. Thus, in vitro exposure of saliva to nine "puffs" of CS also showed a distinct increase in protein carbonyls. Ascorbate and desferrioxamine mesylate had little effect on protein carbonyl formation, while GSH and N-acetylcysteine considerably inhibited the accumulation of protein carbonyls due to CS exposure. Following the exposure to CS, the activities of several salivary enzymes-amylase, lactic dehydrogenase (LDH), and acid phosphatase-were found to be significantly reduced (34, 57, and 77%, respectively). However, CS had no effect on the activities of aspartate aminotransferase and alkaline phosphatase. Addition of 1 mM of GSH and N-acetylcysteine considerably protected LDH and amylase activities, suggesting that sulfhydryl groups are affected in LDH and amylase. On the other hand, addition of 1 mM ascorbate caused a further loss of LDH and amylase activities, which could be partially prevented by the addition of desferrioxamine mesylate, implicating metal-catalyzed oxidation processes. Finally, loss of acid phosphatase activity was completely unaffected by any of the above antioxidants. It is concluded that the loss of salivary enzyme activities may be due to various agents in the CS that affect the enzyme activities via different mechanisms.