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Category: neuroscience – Page 4

Dendrite-Targeting Inhibitory Interneurons Form Biased Circuits with Deep and Superficial Pyramidal Cells in Hippocampal CA1

JNeurosci: Johantges et al. used mice to study excitatory and inhibitory synaptic connections in the CA1 region, creating a circuit map with cell-type resolution that will guide future research on how the hippocampus supports learning and memory.

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In the CA1 hippocampus, pyramidal cells (PCs) can be classified as deep or superficial based on their radial position within the stratum pyramidale. Deep and superficial PCs form biased circuits with perisomatic-targeting PV+ basket cells, but it is unknown if such cell-type–specific circuit motifs extend to dendrite-targeting interneurons. Using male and female mice, we investigated synaptic connectivity and physiology in brain slices from four transgenic lines thought to capture distinct subsets of interneurons: SST-IRES-Cre, Nkx2.1-Cre, Chrna2-Cre, and Htr3a-GFP. First, we found that oriens-lacunosum moleculare (OLM) cells captured by the Chrna2-Cre line are a subset of Htr3a-GFP+ cells in the hippocampus. This novel finding is consistent with previous work showing Nkx2.1-Cre OLM cells are distinct from both Chrna2-Cre and Htr3a-GFP+ OLM cells.

Clinical Reasoning: A 49-Year-Old Man With Meningoencephalitis and Persistent Altered Mental Status

Cannabis use is common among those with mental health conditions, and many people report using cannabis to manage mental health symptoms.

It is important for clinicians to understand the lack of clear benefits of cannabis for mental health conditions and the potential for substantial adverse effects.

📌 This Review summarizes the current evidence on the effects of cannabis on commonly encountered mental health conditions and provides clinicians with basic information about cannabis pharmacology and biology.

Tubulin prevents toxic protein clump formation

“This led us to the following idea: what if instead of preventing the formation of droplets, we created conditions that would drive Tau and alpha synuclein inside the droplets toward their healthy path, discouraging them from taking the disease path?” said a co-corresponding author of the work.

The team worked with biochemical and biophysical techniques, high-resolution microscopy and neuronal-based assays to investigate tubulin’s role in modulating and preventing the formation of toxic aggregates in droplets.

The researchers show that Tubulin modulates Tau:αSyn condensates by promoting microtubule interactions and inhibiting homotypic and heterotypic pathological oligomers. Tubulin partitioning into condensates promotes microtubule polymerization and prevents Tau and αSyn oligomerization.

In the absence of Tubulin, Tau-driven condensation accelerates formation of pathogenic Tau:αSyn heterodimers and amyloid fibrils. The authors also identify distinct Tau and αSyn structural states in pathological Tubulin-absent versus physiological Tubulin-rich condensates.

“When tubulin levels are low, as it has been found in Alzheimer’s disease, microtubules are less abundant and Tau and alpha synuclein can form toxic aggregates,” the author said. “But when tubulin is present, Tau and alpha‑synuclein shift away from harmful aggregates and instead promote the assembly of healthy microtubules,” the author said. “Tubulin redirects the activity of these proteins by giving them something productive to do.” ScienceMission sciencenewshighlights.

Researchers have discovered a potential new strategy to fight back against Alzheimer’s and Parkinson’s diseases, conditions that are linked to the toxic accumulation of Tau and alpha synuclein protein clumps in the brain. The team reports in Nature Communications that tubulin, the building block of microtubules, the cell’s internal ‘railway tracks,’ can stop Tau and alpha synuclein from forming toxic clumps and instead steer them into their normal, healthy roles.

Continue reading “Tubulin prevents toxic protein clump formation” | >

Abstract: Glioblastoma remains profoundly resistant to current immunotherapeutic strategies

Here, Fanghui Lu & team report OLIG2, a master transcription factor in glioblastoma stem cells, enables immune evasion by suppressing CXCL10. And, targeting OLIG2 overcomes immunotherapy resistance and improves survival.

1Department of Cancer Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

2Department of Neurosurgery, Key Laboratory of Major Brain Disease and Aging Research (Ministry of Education), The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

3School of Basic Medical Sciences, Chongqing Medical University, Chongqing, China.

New cellular immunotherapy approach for Alzheimer’s disease

Alzheimer’s disease starts with a sticky protein called amyloid beta that builds up into plaques in the brain, setting off a chain of events that results in brain atrophy and cognitive decline. Microglia, immune cells that reside in the brain, are responsible for removing brain waste but can become dysfunctional when overwhelmed in the context of neurodegenerative disease.

To reduce the cleaning burden on microglia, first author transformed astrocytes, the most abundant cell type in the brain, into amyloid-cleaning machines. The author custom-designed and delivered a gene to astrocytes that codes for the chimeric antigen receptor (CAR) via a harmless virus injected into mice. The CAR, now present on the surface of astrocytes, enabled the cells to capture and engulf amyloid beta proteins. With their newly acquired ability, the astrocytes — generally responsible for keeping the brain tidy — concentrated their efforts on only cleaning amyloid beta plaques in mice prone to its buildup.

Mice carrying genetic mutations that increase people’s risk of developing Alzheimer’s disease develop amyloid beta plaques that saturate the brain by six months of age. The author injected two groups of mice with the virus carrying the CAR-expressing gene: young mice before they developed plaques and older mice with brains saturated with plaques, then, waited three months.

As the younger mice aged, the CAR-astrocytes prevented amyloid beta plaque development. At nearly six months of age, when untreated mice normally have brains saturated with harmful plaques, brains of treated mice were plaque-free. Meanwhile, older mice with plaque-saturated brains at the time of treatment saw a 50% reduction in the amount of amyloid beta plaques compared to mice receiving an injection of a virus lacking the CAR gene.

The researchers have filed a patent related to the approach used to engineer CAR-astrocytes.

“Consistent with the antibody drug treatments, this new CAR-astrocyte immunotherapy is more effective when given in the earlier stages of the disease,” said a co-author on the paper. “But where it differs, and where it could make a difference in clinical care, is in the single injection that successfully reduced the amount of harmful brain proteins in mice.” ScienceMission sciencenewshighlights.

Continue reading “New cellular immunotherapy approach for Alzheimer’s disease” | >

Neural crest gene regulatory networks as drivers of development, diversification and disease

Neural crest cells (NCCs) are multipotent stem cells whose activation, migration and diversification are tightly controlled by gene regulatory networks that shape NCC function in vertebrate development, evolution, tissue repair and disease.

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