Alpha-synuclein-induced nigrostriatal degeneration and pramipexole treatment disrupt frontostriatal plasticity.

Parkinson's disease is characterized by the degeneration of substantia nigra pars compacta (SNc) dopaminergic neurons, leading to motor and cognitive symptoms. Numerous cellular and molecular adaptations following neurodegeneration or dopamine replacement therapy (DRT) have been described in motor networks but little is known regarding associative basal ganglia loops. This study investigated the contributions of nigrostriatal degeneration and pramipexole (PPX) on neuronal activity in the orbitofrontal cortex (OFC), frontostriatal plasticity, and markers of synaptic plasticity.

The State of the Dopaminergic and Glutamatergic Systems in the Valproic Acid Mouse Model of Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a progressive neurodevelopmental disorder mainly characterized by deficits in social communication and stereotyped behaviors and interests. Here, we aimed to investigate the state of several key players in the dopamine and glutamate neurotransmission systems in the valproic acid (VPA) animal model that was administered to E12.5 pregnant females as a single dose (450 mg/kg).

Proteins Associated with Phagocytosis Alteration in Retinal Pigment Epithelial Cells Derived from Age-Related Macular Degeneration Patients.

Age-related macular degeneration (AMD) is partially characterized by retinal pigment epithelial (RPE) cell dysfunction. This study focused on phagocytosis activity and its involvement in AMD. Phagocytic activity was analyzed by flow cytometry using porcine photoreceptor outer segment (POS) and fluorescent beads in basal and under oxidative stress condition induced by Fe-NTA in fifteen hiPSC-RPE cell lines (six controls, six atrophic AMD and three exudative AMD).

Major motor and gait deficits with sexual dimorphism in a Shank3 mutant mouse model.

Background: Contrasting findings were reported in several animal models with a Shank3 mutation used to induce various autism spectrum disorder (ASD) symptoms. Here, we aimed at investigating behavioral, cellular, and molecular consequences of a C-terminal (frameshift in exon 21) deletion in Shank3 protein in mice, a mutation that is also found in clinical conditions and which results in loss of major isoforms of Shank3. A special focus was made on cerebellar related parameters.

Sex-dependent behavioral deficits and neuropathology in a maternal immune activation model of autism.

Infections during gestation and the consequent maternal immune activation (MIA) increase the risk of developing neuropsychiatric disorders in infants and throughout life, including autism spectrum disorders (ASD). ASD is a neurodevelopmental disorder that affects three times more males than females and is mainly characterized by deficits in social communication and restricted interests. Consistent findings also indicate that ASD patients suffer from movement disorders, although these symptoms are not yet considered as diagnosis criteria.

Cell Cycle Changes after Glioblastoma Stem Cell Irradiation: The Major Role of RAD51.

"Glioma Stem Cells" (GSCs) are known to play a role in glioblastoma (GBM) recurrence. Homologous recombination (HR) defects and cell cycle checkpoint abnormalities can contribute concurrently to the radioresistance of GSCs. DNA repair protein RAD51 homolog 1 (RAD51) is a crucial protein for HR and its inhibition has been shown to sensitize GSCs to irradiation.

hRPE cells derived from induced pluripotent stem cells are more sensitive to oxidative stress than ARPE-19 cells.

The ARPE-19 cell line is currently used as an in vitro model for retinal diseases such as age-related degeneration (AMD). However, several studies have pointed out morphological and genetic differences between ARPE-19 cells and human fetal or adult retinal pigment epithelial (hRPE) cells. This study aims to compare ARPE-19 cells to hRPE cells derived from human induced pluripotent stem cells (hiPSCs) in both normal and oxidative stress conditions induced by Fe-NTA treatment.

Motor Impairments Correlate with Social Deficits and Restricted Neuronal Loss in an Environmental Model of Autism.

Background: Motor impairments are amongst the earliest and most consistent signs of autism spectrum disorders but are not used as diagnostic criteria. In addition, the relationship between motor and cognitive impairments and their respective neural substrates remain unknown.

Methods: Here, we aimed at determining whether a well-acknowledged animal model of autism spectrum disorders, the valproic acid model, displays motor impairments and whether they may correlate with social deficits and neuronal loss within motor brain areas.

Crizotinib targets in glioblastoma stem cells.

Glioblastoma stem cells (GSCs) are believed to be involved in the mechanisms of tumor resistance, therapeutic failures, and recurrences after conventional glioblastoma therapy. Therefore, elimination of GSCs might be a prerequisite for the development of successful therapeutic strategies. ALK, ROS1, and MET are targeted by Crizotinib, a tyrosine kinase inhibitor which has been approved for treatment of ALK-rearranged non-small-cell lung cancer.

A radiosensitizing effect of RAD51 inhibition in glioblastoma stem-like cells.

Background: Radioresistant glioblastoma stem cells (GSCs) contribute to tumor recurrence and identification of the molecular targets involved in radioresistance mechanisms is likely to enhance therapeutic efficacy. This study analyzed the DNA damage response following ionizing radiation (IR) in 10 GSC lines derived from patients.

Methods: DNA damage was quantified by Comet assay and DNA repair effectors were assessed by Low Density Array.

Selective release of a cyclopamine glucuronide prodrug toward stem-like cancer cell inhibition in glioblastoma.

Recent data suggest that inhibition of the Hedgehog pathway could be a therapeutic target for glioblastoma. Alkaloid cyclopamine inhibits Hedgehog signaling, depleting stem-like cancer cells derived from glioblastoma. However, this compound is toxic for somatic stem cells, preventing its use for clinical applications.