The laminar position, morphology, and gene expression profiles of cortical astrocytes are influenced by time of birth from ventricular/subventricular progenitors.

Astrocytes that reside in superficial (SL) and deep cortical layers have distinct molecular profiles and morphologies, which may underlie specific functions. Here, we demonstrate that the production of SL and deep layer (DL) astrocyte populations from neural progenitor cells in the mouse is temporally regulated. Lineage tracking following in utero and postnatal electroporation with PiggyBac (PB) EGFP and birth dating with EdU and FlashTag, showed that apical progenitors produce astrocytes during late embryogenesis (E16.5) that are biased to the SL, while postnatally labeled (P0) astrocytes are biased to the DL. In contrast, astrocytes born during the predominantly neurogenic window (E14.5) showed a random distribution in the SL and DL. Of interest, E13.5 astrocytes birth dated at E13.5 with EdU showed a lower layer bias, while FT labeling of apical progenitors showed no bias. Finally, examination of the morphologies of "biased" E16.5- and P0-labeled astrocytes demonstrated that E16.5-labeled astrocytes exhibit different morphologies in different layers, while P0-labeled astrocytes do not. Differences based on time of birth are also observed in the molecular profiles of E16.5 versus P0-labeled astrocytes. Altogether, these results suggest that the morphological, molecular, and positional diversity of cortical astrocytes is related to their time of birth from ventricular/subventricular zone progenitors.

Animal models of Parkinson's disease: bridging the gap between disease hallmarks and research questions.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. More than 200 years after its first clinical description, PD remains a serious affliction that affects a growing proportion of the population. Prevailing treatments only alleviate symptoms; there is still neither a cure that targets the neurodegenerative processes nor therapies that modify the course of the disease. Over the past decades, several animal models have been developed to study PD. Although no model precisely recapitulates the pathology, they still provide valuable information that contributes to our understanding of the disease and the limitations of our treatment options. This review comprehensively summarizes the different animal models available for Parkinson's research, with a focus on those induced by drugs, neurotoxins, pesticides, genetic alterations, α-synuclein inoculation, and viral vector injections. We highlight their characteristics and ability to reproduce PD-like phenotypes. It is essential to realize that the strengths and weaknesses of each model and the induction technique at our disposal are determined by the research question being asked. Our review, therefore, seeks to better aid researchers by ensuring a concrete discernment of classical and novel animal models in PD research.

Millimetric scale two-photon Bessel-Gauss beam light sheet microscopy with three-axis isotropic resolution using an axicon lens.

Significance: Typical light sheet microscopes suffer from artifacts related to the geometry of the light sheet. One main inconvenience is the non-uniform thickness of the light sheet obtained with a Gaussian laser beam. Aim: We developed a two-photon light sheet microscope that takes advantage of a thin and long Bessel-Gauss beam illumination to increase the sheet extent without compromising the resolution. Approach: We use an axicon lens placed directly at the output of an amplified femtosecond laser to produce a long Bessel-Gauss beam on the sample. We studied the dopaminergic system and its projections in a whole cleared mouse brain. Results: Our light sheet microscope allows an isotropic resolution of 2.4 µm in all three axes of the scanned volume while keeping a millimetric-sized field of view, and a fast acquisition rate of up to 34 mm2/s. With slight modifications to the optical setup, the sheet extent can be increased to 6 mm. Conclusion: The proposed system's sheet extent and resolution surpass currently available systems, enabling the fast imaging of large specimens.

Neuroprotective benefits of grape seed and skin extract in a mouse model of Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of midbrain dopaminergic (mDA) neurons in the substantia nigra pars compacta, and it involves oxidative stress. Our goal was to evaluate the neuroprotective effect of Vitis vinifera red grape seed and skin extract (GSSE) in a model of Parkinson's disease. GSSE is very rich in phenolic compounds, such as flavonoids, anthocyanins, catechins and stilbenes, which are present in the pulp, seeds, and leaves of the fruit. GSSE is known for its antioxidant properties and has shown beneficial effects against oxidative injury in different organs, such as the kidneys, liver, heart and brain. In this study, we revealed the neuroprotective effect of GSSE on midbrain dopaminergic neurons both in vitro and in vivo. We used the neurotoxin 6-hydroxydopamine (6-OHDA), which induces oxidative damage and mimics the degeneration of dopaminergic neurons observed in Parkinson's disease. We found that GSSE was effective in protecting dopamine neurons from 6-OHDA toxicity by reducing apoptosis, the level of reactive oxygen species (ROS) and inflammation. Furthermore, we found that GSSE treatment efficiently protected against neuronal loss and improved motor function in an in vivo 6-OHDA model of Parkinson's disease (PD). Altogether, our results show that GSSE acts at multiple levels to protect dopamine neurons from degeneration in a model of PD.