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The metabolic engine of cognition: microglia-neuron interactions in health, ageing and disease

2 weeks ago
Cognitive impairment is associated with perturbations of fine-tuned neuroimmune interactions. At the molecular level, alterations in cellular metabolism can compromise brain function, driving structural damage and cognitive deficits. In this Review, we focus on the bidirectional interactions between microglia, the brain-resident immune cells and neurons to dissect the metabolic determinants of brain resilience and cognition. We first outline these metabolic pathways during development and adult...
Evridiki Asimakidou

Progressive remote memory decline coincides with parvalbumin interneuron hyperexcitability and enhanced inhibition of cortical engram cells in a mouse model of Alzheimer's disease

2 weeks ago
Patients with Alzheimer's disease (AD) initially show temporally graded retrograde amnesia, which gradually progresses into more severe retrograde amnesia. Although mouse models of AD have provided insight into neurobiological mechanisms contributing to impaired formation and retrieval of new memories, the process underlying the progressive loss of remote memories in AD has remained elusive. Here, we demonstrate age-dependent remote memory decline in APP/PS1 mice, which coincides with...
Julia J van Adrichem

The efficacy of longevity interventions in Caenorhabditis elegans is determined by the early life activity of RNA splicing factors

2 weeks ago
Geroscience aims to target the aging process to extend healthspan. However, even isogenic individuals show heterogeneity in natural aging rate and responsiveness to pro-longevity interventions, limiting translational potential. Using RNAseq analysis of young, isogenic, subpopulations of Caenorhabditis elegans selected solely on the basis of the splicing pattern of an in vivo minigene reporter that is predictive of future life expectancy, we find a strong correlation in young animals between...
Sneha Dutta

Variations in body condition score, inflammatory and metabolic biomarkers predict cognitive changes in clinically healthy senior cats

2 weeks ago
CONCLUSION AND RELEVANCE: Findings suggest that changes in physiological parameters describing patterns of chronic inflammation are associated with measurable cognitive changes in aging cats, in the absence of overt clinical disease, which is consistent with the concept of inflammaging. Routine monitoring of standard bloodwork and BCS may offer an accessible means of tracking chronic subclinical inflammation and predicting cognitive aging in senior feline patients. These results highlight the...
Holly Memoli

Magnetic resonance imaging analysis for Alzheimer's disease diagnosis using artificial intelligence: Methods, challenges, and opportunities

2 weeks 1 day ago
Alzheimer's disease(AD) is the most common cause of dementia and affects millions of people worldwide. The early and accurate diagnosis of AD is crucial for timely intervention and disease management. Magnetic resonance imaging (MRI) is a widely used noninvasive technique for assessing brain structure and function in patients with AD. However, conventional MRI analysis methods are often subjective, time-consuming, and depend on expert knowledge. Artificial intelligence (AI), particularly deep...
Qiye Shi

A unified mechanism for mitochondrial damage sensing in PINK1-Parkin-mediated mitophagy

2 weeks 1 day ago
Damaged mitochondria can be cleared from the cell by mitophagy, using a pathway formed by the recessive Parkinson's disease genes PINK1 and Parkin. Whether the pathway senses diverse forms of mitochondrial damage via a common mechanism, however, remains uncertain. Here, using a novel Parkin reporter in genome-wide screens, we identified that diverse forms of mitochondrial damage converge on loss of mitochondrial membrane potential (MMP) to activate PINK1. Loss of MMP, but not the presequence...
Julia A Thayer

Cortical PV interneurons regulate loudness perception and sustainably reverse loudness hypersensitivity

2 weeks 1 day ago
Parvalbumin-expressing inhibitory neurons (PVNs) stabilize cortical network activity, generate gamma rhythms, and regulate experience-dependent plasticity. We found that PVNs act like a volume knob in the mouse auditory cortex (ACtx), bi-directionally adjusting neural and perceptual sensitivity to sound level over a 20 dB range. PVN-based gain adjustments were "sticky," such that a single bout of PVN activation at 40 Hz-but not at 1 or 70 Hz-sustainably dampened ACtx sound responsiveness,...
Kameron K Clayton