Author | Olivia
Editor | Valuri Abstract
Neuroscientists at the University of Lausanne and the Wyss Center for Biological and Neuroengineering in Geneva have discovered a new type of cell that is essential for brain function – glutamatergic astrocytes. This cell is intermediate between two common brain cell types, neurons, and glial cells, and is also known as a third cell type.
Keywords
Glial cells, Neurons, Glutamate, Parkinson's disease (PD), Central Nervous System (CNS)
Introduction to the experiment
To verify whether astrocytes can also release neurotransmitters like neurons, scientists studied the gene expression of astrocytes. They want to find the necessary mechanisms for the rapid secretion of glutamate, the main neurotransmitter used by neurons.
The team used single-cell transcriptomics techniques and localized to different hippocampal loci. Transcripts of vesicular glutamate transporter protein 1 (VGLUT1) are present in this subpopulation of astrocytes. VGLUT1 loads glutamate into synaptic vesicles and facilitates its release across the synaptic gap.
Glutamatergic astrocytes promote memory, participate in motor control, and play an important role in the protection of the central nervous system, providing new insights into the role of astrocytes in central nervous system (CNS) disorders. Such as epilepsy, Alzheimer's disease, Parkinson's disease, and others.
Experimental Procedure
First, the scientists used mice carrying human glial fibrillary acidic protein (GFAP) to verify whether glutamatergic astrocytes can release glutamate at the same rate as synaptic transmission. Next, the scientists prepared tissue-dissociated single-cell suspensions from mouse brain regions and digested the tissues using papain at 37°C, followed by three rounds of abrasive mechanical dissociation using serum pipettes.
The researchers used FACS isolation of astrocytes and genomic PCR assays to exclude dead cells. The team used GluSnFR-based in situ and in vivo imaging, which allows visualization of glutamate released from vesicles in brain tissue and in living mice.
The scientists then used acute brain slice preparations to prepare acute hippocampal or midbrain slices from transgenic mouse lines or WT mice and used them for patch sequencing, two-photon imaging, and synaptic electrophysiology experiments.
The results show that glutamatergic astrocytes respond to selective stimuli with rapid glutamate release, which occurs in spatially separated regions of the cell, like the synapse of a neuron. In addition, the release of glutamate has an effect on synaptic transmission, which the team demonstrated by inhibiting VGLUT expression in these cells.
Glutamatergic astrocytes regulate neuronal activity, controlling neuronal communication and excitation levels. Studies on mice have shown that without this functional mechanism, the delayed potential, a neural process in the memory mechanism is impaired, and the mice's memory is impaired as a result.
The study also found that such glutamatergic astrocytes are associated with brain diseases. By specifically knocking out VGLUT1 in glutamatergic astrocytes, the team found that this led to increased seizures.
Summary
In the future, scientists will determine the overall distribution of glutamatergic astrocytes and their all-encompassing role, and better understand why this atypical astrocyte population exists and how its anatomical and functional significance contributes to defined pathologic CNS conditions.
The scientists said, "Between neurons and astrocytes, we have discovered a novel cell whose discovery opens up tremendous research prospects. Our next study will explore the potential protective role of this cell against memory impairment in Alzheimer's disease, as well as its role in other regions and pathologies."
The scientists wrote at the conclusion of their paper, "Future studies are expected to yield CNS-wide maps that will help to determine the overall distribution of glutamatergic astrocytes and their full range of roles, and to better understand why this atypical astrocyte population exists and the specific ways in which it is anatomically and functionally integrated into CNS system circuits, and whether and how its altered properties contribute to pathologic CNS disorders."
The study also shows that glutamatergic astrocytes are also involved in the regulation of motor-controlled brain circuits and could provide new targets for Parkinson's disease. These cells promote memory capacity, and brain control of movement, and suppress seizures.
The discovery of this atypical subpopulation of specialized cells has provided scientists with new insights into the complex role of astrocytes in Central Nervous System (CNS) physiology and disease, highlighting a potential therapeutic target.
Comments