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Preparation of Acute Hippocampal Slices from Rats and Transgenic Mice for the Study of Synaptic Alterations during Aging and Amyloid Pathology

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Altered NPTX2 dynamics associated with impaired cognitive aging.

Rebecca P Haberman^1,2, Ana Delgado³, Meifang Xiao³

¹Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD, USA.

Biorxiv : the Preprint Server for Biology

|September 26, 2025

Summary

Successful cognitive aging is linked to higher neuronal pentraxin 2 (NPTX2) levels. Impaired aging brains fail to increase NPTX2 with memory tasks, unlike healthy aging brains.

Keywords:

Biological Sciences Neuronal pentraxin 2 Neuroscience age related cognitive decline hippocampal hyperactivity

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Published on: May 12, 2015

Area of Science:

Neuroscience
Aging Research
Synaptic Plasticity

Background:

Brain aging affects synaptic integrity and neural activity, impacting cognition.
Neuronal pentraxin 2 (NPTX2) changes in cerebrospinal fluid may indicate synaptic damage and cognitive decline in Alzheimer's disease (AD).
Human studies struggle to distinguish normal aging from disease-related processes.

Purpose of the Study:

Investigate neural substrates underlying aging's role in neurodegeneration risk.
Examine the relationship between NPTX2 levels and cognitive function across the aging spectrum.
Differentiate adaptive changes in aging from disease-specific alterations.

Main Methods:

Utilized a well-characterized rat model with individual memory differences during aging.
Assessed NPTX2 levels in relation to cognitive performance in young, aged, and cognitively impaired rats.
Examined NPTX2 response to pharmacological neural activity engagement and hippocampus-dependent memory tasks.

Main Results:

Cognitively successful aging correlated with elevated NPTX2 levels compared to young or impaired subjects.
Pharmacological stimulation increased NPTX2 in all rats.
Cognitively impaired aged rats showed a blunted NPTX2 response during a memory task.

Conclusions:

NPTX2 levels are associated with distinct cognitive outcomes during aging.
Successful neurocognitive aging involves an adaptive increase in NPTX2.
This adaptive upregulation differs from persistent youthful synaptic dynamics or disease-related decline.