Morphological impairments in microglia precede age-related neuronal degeneration in senescence-accelerated mice
Sanae Hasegawa-Ishii1, Shiro Takei, Yoichi Chiba
1Department of Pathology, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Japan.
Abstract:
The ageing brain is characterized by degenerative changes in both neurons and glia. Although neurons are known to lose dendritic complexity with ageing, age-related changes in the morphology of microglia have not been well documented. We investigated potential age-related changes in microglial morphology using mouse models. Senescence-accelerated mouse prone 10 (SAMP10) in which neuronal degeneration begins to appear around 8 months of age and becomes progressively remarkable with advancing age was used as a model of brain ageing. Senescence-accelerated mouse resistant 1 (SAMR1) in which age-related neuronal changes are inconspicuous was used as usual-ageing controls. Hippocampal sections prepared from 3-, 8- and 14-month-old SAMP10 and 3-, 8-, 14- and 24-month-old SAMR1 mice were stained immunohistochemically with anti-Iba-1 antibody to highlight microglia. Stick figures of individual microglia reflecting the length and complexity of cytoplasmic processes were made by camera lucida drawing. Parameters representing morphological features of microglia were quantified using an image analyzer: area of convex closure, cell body area, number of primary processes, maximal branch order, combined projection length, number of segments and number of tips. Pathological changes of processes such as beading and clusters of fragmented twigs were counted. In microglia of 3- and 8-month-old SAMP10 mice, combined projection length was shorter and numbers of segments and tips were smaller than those in age-matched SAMR1 mice. Similar changes were detected in SAMR1 mice at age 14 months and older. Microglia of SAMP10 mice at all ages were characterized by having frequent pathological changes in processes, which were not remarkable in SAMR1 mice at any age. These morphological abnormalities in microglia of SAMP10 mice preceded the onset of neuronal degeneration and may lead to making brain tissue less protective to neurons. We propose that preceding abnormalities in microglia may contribute to the vulnerability to age-related neuronal degeneration in SAMP10 mice.
Insights
Ageing causes microglial cells in the brain to change shape, showing abnormalities before neuronal degeneration occurs. These microglial changes may increase brain vulnerability to ageing effects.
Area of Science:
- Neuroscience
- Gerontology
- Cell Biology
Background:
- The ageing brain exhibits neuronal and glial degeneration.
- Neuronal dendritic complexity decreases with age, but microglial morphology changes are less understood.
Purpose of the Study:
- To investigate age-related morphological changes in microglia using mouse models.
- To determine if microglial abnormalities precede neuronal degeneration in ageing.
Main Methods:
- Utilized senescence-accelerated mouse prone 10 (SAMP10) and resistant 1 (SAMR1) models for brain ageing.
- Immunohistochemical staining with anti-Iba-1 antibody to visualize microglia in hippocampal sections.
- Quantified microglial morphology parameters (e.g., process length, branching, pathological changes) using image analysis.
Main Results:
- Microglia in SAMP10 mice showed reduced process length and fewer segments/tips compared to SAMR1 controls.
- Pathological changes in microglial processes were frequent in SAMP10 mice at all ages.
- These microglial abnormalities were observed before the onset of significant neuronal degeneration.
Conclusions:
- Ageing induces significant morphological alterations in microglia.
- Abnormal microglial morphology precedes neuronal degeneration in the SAMP10 ageing model.
- These microglial changes may contribute to neuronal vulnerability during brain ageing.
