Date of Award

2026

Degree Name

Biological Sciences

College

College of Science

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Dr. Nadja Spitzer

Second Advisor

Dr. Chris Risher

Third Advisor

Dr. Cheyenne Tait

Abstract

Silver nanoparticles (AgNPs) are widely incorporated into consumer and medical products due to their antibacterial properties, increasing the potential for chronic exposure. AgNPs can be released into the environment, enter the body through ingestion or inhalation, cross the blood-brain barrier (BBB), and bioaccumulate in brain tissue. Previous in vitro studies demonstrate that AgNP exposure disrupts cytoskeletal organization and induces neurite collapse in neural cells, suggesting vulnerability of cytoskeleton-dependent structures in vivo. Astrocytes, through their perisynaptic astrocytic processes (PAPs) and perivascular endfeet, play critical roles in maintaining synaptic and neurovascular architecture, both of which rely heavily on cytoskeletal integrity. This study examined the effects of acute and bioaccumulative oral AgNP exposure (25 mg and 100 mg/kg; resulting in 10-40 ng/g brain silver concentrations) on tripartite synapse microarchitecture, astrocyte-vascular interactions, and the induction of gliosis in the rat hippocampus and striatum. Using fluorescent immunohistochemistry and confocal imaging, synaptic and astrocytic markers were quantified based on fluorescence intensity and colocalization to assess changes in tripartite synapse microarchitecture and astrocytic-vascular interactions. Acute expose increased presynaptic and astrocytic markers and enhanced PAP-synapse colocalization in the hippocampus, suggesting a compensatory response. In contrast, bioaccumulative exposure reduced presynaptic and astrocytic markers and decreased colocalization in the hippocampus, indicating disruption of tripartite synapse microarchitecture. Despite these synaptic alterations, astrocytic-vascular interactions were preserved and no gliosis was observed. Collectively, these findings demonstrate that oral AgNP exposure induces region-and time-dependent disruption of astrocyte-synapse microarchitecture in vivo, identifying synaptic microarchitecture as a sensitive target of AgNP neurotoxicity which has potential implications for synaptic stability and neurological health under chronic low-level conditions.

Subject(s)

Neurosciences.

Neurology.

Biology.

Synapses.

Astrocytes.

Astrocytes -- Physiology.

Blood-brain barrier.

Nanoparticles.

Neurotoxicology.

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