Bilateral upregulation of α-synuclein expression in the mouse substantia nigra by intracranial rotenone treatment.

The pesticide rotenone has been shown to cause systemic inhibition of mitochondrial complex I activity, with consequent degeneration of dopamine neurons along the nigrostriatal pathway, as observed in Parkinson's disease (PD). Recently, intracranial infusion of rotenone was found to increase the protein levels of the Lewy body constituents, α-synuclein and small ubiquitin-related modifier-1(SUMO-1), in the lesioned hemisphere of the mouse brain. These findings are supportive of a mouse model of PD, but information about the dopamine-synthesizing enzyme, tyrosine hydroxylase (TH), an essential marker of dopaminergic status, was not reported.

Altered melatonin MT receptor expression in the ventral midbrain following 6-hydroxydopamine lesions in the rat medial forebrain bundle.

The indoleamine hormone melatonin protects dopamine neurons in the rat nigrostriatal pathway following 6-hydroxydopamine lesioning, and an increase in striatal melatonin levels has been detected in this model of Parkinson's disease. Melatonin induces the expression of tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, in the ventral midbrain, where G protein-coupled melatonin receptors are present. Based on the interaction between the melatonergic and dopaminergic systems, we hypothesized that 6-hydroxydopamine-induced degeneration of dopamine neurons would affect the expression of melatonin receptors in the nigrostriatal pathway.

Chronic low-dose melatonin treatment maintains nigrostriatal integrity in an intrastriatal rotenone model of Parkinson's disease.

Parkinson's disease is a major neurodegenerative disorder which primarily involves the loss of dopaminergic neurons in the substantia nigra and related projections in the striatum. The pesticide/neurotoxin, rotenone, has been shown to cause systemic inhibition of mitochondrial complex I activity in nigral dopaminergic neurons, with consequent degeneration of the nigrostriatal pathway, as observed in Parkinson's disease. A novel intrastriatal rotenone model of Parkinson's disease was used to examine the neuroprotective effects of chronic low-dose treatment with the antioxidant indoleamine, melatonin, which can upregulate neurotrophic factors and other protective proteins in the brain.

Induction of neurotrophic and differentiation factors in neural stem cells by valproic acid.

Valproic acid (VPA), a short-chain fatty acid, is used clinically as an anticonvulsant and mood stabilizer. Valproic acid also inhibits histone deacetylase activity, which is associated with histone hyperacetylation and changes in gene expression. In this study, we examined the effects of VPA on the expression of selected neurotrophic and differentiation factors in C17.

HDAC inhibitor M344 suppresses MCF-7 breast cancer cell proliferation.

Histone deacetylase (HDAC) inhibitors represent a novel class of drugs that selectively induce cell cycle arrest and apoptosis in transformed cells. This study examined, for the first time, the effects of the relatively new HDAC inhibitor, M344 [4-dimethylamino-N-(6-hydroxycarbamoylhexyl)-benzamide], on the proliferation of MCF-7 breast cancer cells. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays revealed significant concentration- and time-dependent decreases in MCF-7 cell proliferation following treatment with M344 (1-100μM).

Valproic acid up-regulates melatonin MT1 and MT2 receptors and neurotrophic factors CDNF and MANF in the rat brain.

We have reported that clinically relevant concentrations of valproic acid (VPA) up-regulate the G-protein-coupled melatonin MT1 receptor in rat C6 glioma cells. To determine whether this effect occurs in vivo, the effects of chronic VPA treatment on the expression of both melatonin receptor subtypes, MT1 and MT2, were examined in the rat brain. Reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR analyses revealed significant increases in MT1 and MT2 mRNA expression in the hippocampus, following VPA (4 mg/ml drinking water) treatment for 17 d.

Impaired spatial and contextual memory formation in galectin-1 deficient mice.

Galectins are a 15 member family of carbohydrate-binding proteins that have been implicated in cancer, immunity, inflammation and development. While galectins are expressed in the central nervous system, little is known about their function in the adult brain. Previously we have shown that galectin-1 (gal-1) is expressed in the adult hippocampus, and, in particular, in putative neural stem cells in the subgranular zone.