Researchers identify an early, neuron-driven mechanism that reshapes glial pruning and drives Alzheimer’s-like pathology in mouse models. Using ExPre/InhiPre reporters, APP/PS1 and 5×FAD mice showed progressive increases in astrocyte- and microglia-mediated elimination of excitatory synapses but reduced removal of inhibitory synapses; astrocytic changes emerged earliest. Chemogenetic modulation demonstrated that glial engulfment is activity-dependent: heightened neuronal firing increases phagocytosis while suppression reduces it. Knocking down the astrocytic phagocytic receptor MEGF10 selectively preserved excitatory synapses, linking activity imbalance (excitatory hyperactivity, inhibitory hypoactivity) to selective synapse loss.
Single-nucleus RNA-sequencing uncovered a novel early-responsive excitatory neuron state (EREN) defined by ectopic Erbb4 expression. CRISPR-mediated Erbb4 deletion restricted to excitatory neurons in 5×FAD mice normalized network activity, prevented abnormal synapse elimination, reduced reactive gliosis and amyloid plaque burden, and rescued cognition. Conversely, Erbb4 overexpression in wild-type excitatory neurons reproduced core AD-like phenotypes without plaques; these effects depended on mTOR signaling. Human transcriptomic mediation analyses place excitatory neuronal ERBB4 upstream of amyloid-tau propagation and cognitive decline. The results position aberrant excitatory neuronal ERBB4 as an early driver of synaptic imbalance and neurodegeneration and nominate ERBB4-mTOR signaling as a potential therapeutic target.
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Researchers are exploring the potential of older gene-editing techniques, such as VIPR, as the next advancement in gene editing technology. These methods could complement or enhance current tools like CRISPR, offering new possibilities for genetic modification. (nytimes.com)
Scientists have identified the tilcayo, a new wildcat species in Bolivia's cloud forests, the first discovery of a new wildcat in over a century. The small, leopard-spotted feline was found after genetic testing revealed it diverged from its closest relative 1.4 million years ago. (scientificamerican.com)
Japan has surpassed 100,000 centenarians for the first time, with a total of 107,677 people aged 100 or older. The increase is attributed to advances in medicine, a healthy diet, and active lifestyles, but poses challenges for social security sustainability. (bbc.com)
A small, spotted tiger cat from Bolivia has been identified as a new species, Leopardus tilcayo, the first discovery of a new cat species in over 100 years. The cat was initially mistaken for a known species but was confirmed as new after detailed analysis and photographs. (nationalgeographic.com)
The Hafnium controversy centers on claims of triggering rapid energy releases through gamma-ray emission from a nuclear isomer, 178m2Hf. These claims, first reported in 1998, remain unproven and widely disputed by experts, with no independent reproduction of the results. (en.wikipedia.org)
Scientists determined that T. Rex had a body temperature of approximately 97 degrees Fahrenheit using geochemistry techniques on fossilized teeth. This finding supports the idea that dinosaurs like T. Rex were warm-blooded rather than cold-blooded reptiles. (nytimes.com)
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