Large-scale death of retinal astrocytes during normal development is non-apoptotic and implemented by microglia DOI Creative Commons
Vanessa M. Puñal, Caitlin E. Paisley, Federica S. Brecha

и другие.

PLoS Biology, Год журнала: 2019, Номер 17(10), С. e3000492 - e3000492

Опубликована: Окт. 18, 2019

Naturally occurring cell death is a fundamental developmental mechanism for regulating numbers and sculpting developing organs. This particularly true in the nervous system, where large of neurons oligodendrocytes are eliminated via apoptosis during normal development. Given profound impact upon these two major populations, it surprising that another type—the astrocyte—has rarely been studied. It presently unclear whether astrocytes subject to significant death, if so, how occurs. Here, we address questions using mouse retinal as our model system. We show total number declines by over 3-fold period spanning postnatal days 5–14. Surprisingly, do not die apoptosis, canonical underlying vast majority death. Instead, find microglia engulf promote their removal. Genetic ablation inhibits astrocyte leading larger population size at end period. However, completely blocked absence microglia, apparently due ability each other. Nevertheless, mice lacking showed anatomical changes network, with functional consequences astrocyte-associated vasculature hemorrhage. These results establish novel modality naturally demonstrate its importance formation integrity gliovascular network.

Язык: Английский

GABAergic Restriction of Network Dynamics Regulates Interneuron Survival in the Developing Cortex DOI Creative Commons

Zhe Ran S. Duan,

Alicia Che,

Philip Chu

и другие.

Neuron, Год журнала: 2019, Номер 105(1), С. 75 - 92.e5

Опубликована: Ноя. 25, 2019

Язык: Английский

Процитировано

90
Caught in vicious circles: a perspective on dynamic feed-forward loops driving oxidative stress in schizophrenia DOI Creative Commons

Michel Cuénod,

Pascal Steullet,

Jan-Harry Cabungcal

и другие.

Molecular Psychiatry, Год журнала: 2021, Номер 27(4), С. 1886 - 1897

Опубликована: Ноя. 10, 2021

Abstract A growing body of evidence has emerged demonstrating a pathological link between oxidative stress and schizophrenia. This identifies as convergence point or “central hub” for schizophrenia genetic environmental risk factors. Here we review the existing experimental translational research pinpointing complex dynamics mechanisms their modulation in relation to pathophysiology. We focus on supporting crucial role either redox dysregulation, N-methyl-D-aspartate receptor hypofunction, neuroinflammation mitochondria bioenergetics dysfunction, initiating “vicious circles” centered during neurodevelopment. These processes would amplify one another positive feed-forward loops, leading persistent impairments maturation function local parvalbumin-GABAergic neurons microcircuits myelinated fibers long-range macrocircuitry. is at basis neural circuit synchronization cognitive, emotional, social sensory deficits characteristic Potential therapeutic approaches that aim breaking these different vicious circles represent promising strategies timely safe interventions. In order improve early detection increase signal-to-noise ratio adjunctive trials antioxidant, anti-inflammatory NMDAR modulator drugs, reverse translation validated circuitry approach needed. The above presented allow identify mechanism based biomarkers guiding stratification homogenous patients groups target engagement required successful clinical trials, paving way towards precision medicine psychiatry.

Язык: Английский

Процитировано

84
Development and plasticity of the corpus callosum DOI Creative Commons
Noelia S. de León-Reyes, Lorena Bragg-Gonzalo, Marta Nieto

и другие.

Development, Год журнала: 2020, Номер 147(18)

Опубликована: Сен. 15, 2020

ABSTRACT The corpus callosum (CC) connects the cerebral hemispheres and is major mammalian commissural tract. It facilitates bilateral sensory integration higher cognitive functions, often affected in neurodevelopmental diseases. Here, we review mechanisms that contribute to development of CC circuits animal models humans. These species comparisons reveal several commonalities. First, there an early period massive axonal projection. Second, a postnatal temporal window, varying between species, which callosal projections are selectively refined. Third, sensory-derived activity influences refinement. We also discuss how defects formation can lead mild or severe congenital malformations.

Язык: Английский

Процитировано

83
Reprogramming reactive glia into interneurons reduces chronic seizure activity in a mouse model of mesial temporal lobe epilepsy DOI Creative Commons
Célia Lentini, Marie d’Orange, Nicolás Marichal

и другие.

Cell stem cell, Год журнала: 2021, Номер 28(12), С. 2104 - 2121.e10

Опубликована: Сен. 29, 2021

Reprogramming brain-resident glial cells into clinically relevant induced neurons (iNs) is an emerging strategy toward replacing lost and restoring brain functions. A fundamental question now whether iNs can promote functional recovery in pathological contexts. We addressed this the context of therapy-resistant mesial temporal lobe epilepsy (MTLE), which associated with hippocampal seizures degeneration GABAergic interneurons. Using a MTLE mouse model, we show that retrovirus-driven expression Ascl1 Dlx2 reactive glia situ, or cortical astroglia grafted epileptic hippocampus, causes efficient reprogramming exhibiting hallmarks These interneurons functionally integrate networks establish synapses onto dentate granule cells. mice significant reduction both number cumulative duration spontaneous recurrent seizures. Thus glia-to-neuron potential disease-modifying to reduce epilepsy.

Язык: Английский

Процитировано

83
Large-scale death of retinal astrocytes during normal development is non-apoptotic and implemented by microglia DOI Creative Commons
Vanessa M. Puñal, Caitlin E. Paisley, Federica S. Brecha

и другие.

PLoS Biology, Год журнала: 2019, Номер 17(10), С. e3000492 - e3000492

Опубликована: Окт. 18, 2019

Naturally occurring cell death is a fundamental developmental mechanism for regulating numbers and sculpting developing organs. This particularly true in the nervous system, where large of neurons oligodendrocytes are eliminated via apoptosis during normal development. Given profound impact upon these two major populations, it surprising that another type—the astrocyte—has rarely been studied. It presently unclear whether astrocytes subject to significant death, if so, how occurs. Here, we address questions using mouse retinal as our model system. We show total number declines by over 3-fold period spanning postnatal days 5–14. Surprisingly, do not die apoptosis, canonical underlying vast majority death. Instead, find microglia engulf promote their removal. Genetic ablation inhibits astrocyte leading larger population size at end period. However, completely blocked absence microglia, apparently due ability each other. Nevertheless, mice lacking showed anatomical changes network, with functional consequences astrocyte-associated vasculature hemorrhage. These results establish novel modality naturally demonstrate its importance formation integrity gliovascular network.

Язык: Английский

Процитировано

82