Project description:RNA-SEQ of dopaminergic neurons from the mid-brain of mice that received one daily intraperitoneal injection of MPTP-HCl (30 mg/kg free base per day) or saline for five consecutive days. Samples were taken 4 days. Murine midbrain dopaminergic neurons that were treated with MPTP-HCl
Project description:In Parkinsonâ??s disease (PD), the progressive loss of substantia nigra dopamine cells has been associated with their vulnerability to oxidative stress, inflammation, and mitochondrial dysfunction. To identify multiple gene transcription alterations that may potentially underlie early stages of related degenerative processes in brain, we used the subcrhonic MPTP mouse model of PD and microarray analysis at 4 days post-MPTP when neurotoxic activity is maximal. Since PD results in gene changes throughout the brain, we assessed MPTP's effects in multiple regions: frontal cortex, striatum and midbrain. Experiment Overall Design: Mus musculus adults were randomly assigned to either MPTP or saline treatment groups. Brain regions of interest (frontal cortex, striatum and midbrain) were dissected from both groups for RNA extraction and hybridization on Affymetrix microarrays.
Project description:In Parkinson’s disease (PD), the progressive loss of substantia nigra dopamine cells has been associated with their vulnerability to oxidative stress, inflammation, and mitochondrial dysfunction. To identify multiple gene transcription alterations that may potentially underlie early stages of related degenerative processes in brain, we used the subcrhonic MPTP mouse model of PD and microarray analysis at 4 days post-MPTP when neurotoxic activity is maximal. Since PD results in gene changes throughout the brain, we assessed MPTP's effects in multiple regions: frontal cortex, striatum and midbrain. Keywords: neurotoxic response
Project description:Neuroinflammation is a common hallmark of neurodegenerative diseases such as Parkinson’s disease (PD). Here, we questioned about the activation state of glial cells along the degeneration process of dopaminergic terminals in the striatum and loss of neuronal cell bodies in the midbrain. We hypothesized that MPTP administration pattern would produce different inflammatory responses that could modify the course of nigrostriatal degeneration. To reproduce the dopaminergic impairment in a PD experimental mouse model, we used two different MPTP-administration patterns: subacute (sMPTP) and chronic (cMPTP). Bulk RNA sequencing of purified midbrain microglia/myeloid cells of sMPTP mice showed an anti-inflammatory phenotype, while midbrain microglia/myeloid cells of cMPTP mice showed a pro-inflammatory and phagocytic phenotype. Midbrain astrocytes presented a phagocytic phenotype in sMPTP mice. In the striatum, microglia presented a continuous pro-inflammatory state in sMPTP and cMPTP conditions. In this region, astrocytes presented a remarkable activated and phagocytic state in sMPTP mice which was attenuated with the chronicity of MPTP administration.
Project description:Inhibition of mechanistic target of rapamycin (mTOR) constitutes the standard of care of lymphangioleiomyomatosis (LAM). However, this treatment does not eradicate diseased cells and some patients show progressive decline of lung function. This study provides preclinical evidence for beneficial therapeutic approaches in combination with rapamycin. LAM tumorigenesis is reduced in vivo (ELT3-V3 tumor xenografts) using approved drugs for other human diseases and targeting monoamine oxidase A (MAO-A; clorgyline) or MAO-B (rasagiline).
Project description:Background: Parkinson's disease (PD), a neurodegenerative disease characterised by bradykinesia, rest tremor and rigidit, affects approximately 6.1 million people worldwide. Although its aetiology was attributed to accumulation of misfolded alpha-synuclein species and subsequent loss of dopaminergic neurons in the substantia nigra, recently, systemic factors contributing to its initiation and progression have gained increasing recognition. Specifically, exosomes, a kind of extracellular vesicles in the size range of ∼30 to ∼200 nm, have been highlighted as crucial mediators in orchestrating the intricate intercellular communication in PD. Among its cargos, miRNAs, with its ability to promote target mRNA degradation and inihibit translation, have been identiifed as promising biomarkers and therpaeutic targets. Nonetheless, the effect of anti-parkinsonism medication on the serum exosome miRNA profiles of PD patients remain lagrely unexplored. Objective: To examine the effects of rasagiline, a potentially neuroprotective monoamine oxidase B inihibitor, on the serum exosome miRNA profile of PD patients.