benzofurans and Parkinsonian-Disorders

Neuroinflammation is often associated with astrocyte and microglial activations particularly in Parkinson's disease (PD) and other brain damage such as Alzheimer's disease. Therefore, the modulation of glial activation offers a possible target for treating PD-associated pathologies. Here, we evaluated the neuroprotective effects of usnic acid, a naturally occurring dibenzofuran derivative found in several lichen species in an acute mouse model of PD. Male mice were administered with vehicle or usnic acid (5 or 25 mg/kg) for 10 consecutive days, and then on day 11, MPTP (20 mg/kg, i.p.) was administered four times (with 2hrs intervals between injections) to induce PD pathologies. It was found that MPTP-induced motor dysfunction and neuronal loss were ameliorated in the usnic acid-treated mice versus vehicle-treated controls. Further study revealed that usnic acid effectively inhibited MPP

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Brain; Disease Models, Animal; Dopaminergic Neurons; Encephalitis; Male; Mice, Inbred C57BL; Neuroglia; Neuroprotective Agents; Nitric Oxide Synthase Type II; Parkinsonian Disorders; Rotarod Performance Test

Topics: Animals; Benzofurans; Brain; Dopamine; Dopamine Agents; Functional Laterality; Indoles; Levodopa; Microdialysis; Oxidopamine; Parkinsonian Disorders; Rats; Serotonin 5-HT4 Receptor Agonists; Serotonin 5-HT4 Receptor Antagonists; Sulfonamides

It was previously reported that cytokines and neurotoxins released from activated inflammatory cells induced the loss of projecting dopaminergic neurons in the substantia nigra, which triggered the pathogenesis of PD. The present study investigated the effect of treatment with tetramethylpyrazine (TMP) on the central cytokine synthesis, striatal dopamine content and glutamatergic transmission, and behavioral performance in the rotarod task in mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment with TMP significantly improved the behavioral performance in the rotarod task in mice injected with MPTP. It also decreased the upregulation of cytokines (tumor necrosis factor-α and interleukin-1β) in the substantia nigra and striatum in these modeled mice. Furthermore, treatment with TMP significantly improved the dopamine deficits and attenuated the upregulation of striatal basal glutamatergic strength in the striatum of mice injected with MPTP. These results indicated that TMP might serve as a novel approach for the treatment of patients with PD.

Topics: Analysis of Variance; Animals; Benzofurans; Corpus Striatum; Cytokines; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; Excitatory Postsynaptic Potentials; In Vitro Techniques; Male; Mice; Neurons; Parkinsonian Disorders; Patch-Clamp Techniques; Postural Balance; Psychomotor Performance; Pyrazines; Quinolines; Vasodilator Agents

In the absence of a cure for Parkinson's disease, development of preventive medications for this devastating disease is particularly encouraged. Dl-3-n-butylphthalide (NBP), an established natural antioxidant for clinical stroke treatment in China, can reportedly reduce beta-amyloid-induced neuronal toxicity in cultured neuronal cells, and attenuate neurodegenerative changes in aged rats. However, whether or not NBP confers neuroprotection in parkinsonian models is still unknown. In this study, we investigated the effects of NBP in rotenone models for Parkinson's diseases. In a cellular model, pretreatment with NBP enhanced cell viability by decreasing nuclear fragmentation, retaining mitochondrial membrane potential, and preventing reactive oxygen species (ROS) from generation. In a rodent model, 2-week treatment with NBP was able to ameliorate apomorphine-evoked rotations by 48% and rescue dopaminergic (DA) neurons by 30% and striatal DA terminal by 49%. Furthermore, NBP upregulated the vesicular monoamine transporter 2 gene expression in vitro and in vivo. Together, NBP protects DA neurons likely by reducing oxidative stress, offering an alternative neuroprotective medication for Parkinson's disease.

Topics: Animals; Antioxidants; Antiparkinson Agents; Benzofurans; Cell Line; Cell Survival; Disease Models, Animal; Dopaminergic Neurons; Humans; Neuroprotective Agents; Parkinsonian Disorders; Rats; Rotenone; Treatment Outcome

To explore the therapeutic potential of imidazoline I(1) receptor ligands in motor dysfunction related to the basal ganglia, rigidity was induced in mice by intraperitoneal administration of reserpine. The imidazoline I(1) receptor agonists moxonidine and tizanidine reduced rigidity in a dose-dependent manner. Although rigidity was reduced by efaroxan (an imidazoline I(1) receptor and alpha(2)-adrenoceptor antagonist) and idazoxan (an imidazoline I(1) and I(2) receptor and alpha(2)-adrenoceptor antagonist), SKF86466 and yohimbine, both of which are alpha(2)-adrenoceptor antagonists with no affinity for imidazoline receptors, also suppressed rigidity, suggesting that activation rather than blockade of imidazoline I(1) receptors contributes to reduction of reserpine-induced muscle rigidity.

Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Antiparkinson Agents; Benzazepines; Benzofurans; Clonidine; Disease Models, Animal; Dose-Response Relationship, Drug; Electromyography; Idazoxan; Imidazoles; Imidazoline Receptors; Injections, Intraperitoneal; Ligands; Male; Mice; Muscle Rigidity; Muscle, Skeletal; Parkinsonian Disorders; Reserpine; Time Factors; Yohimbine