Anxiety Disorders

Stress and Stress Susceptibility Effects on the Motor Cortex and its Function

Jessica Nye, PhD
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microglia-neuron-alzheimer-disease
Alzheimers disease. Computer illustration of a healthy neuron (left), a neuron with amyloid plaques (yellow, centre), and a dead neuron being digested by microglia cells (red, right).
Male mice were exposed to chronic stress using a social defeat stress experiment. Mice were assessed for behavioral deviations and impacts to motor learning after the stress experiment as well as neural changes due to stress.

Mice with high susceptibility to stress were found to have astrogliosis, altered microglia, and increased microglia-neuron interaction in the motor cortex. These findings were published in Translational Psychiatry.

Male mice (N=54) were exposed to chronic stress using a social defeat stress experiment. Mice were assessed for behavioral deviations and impacts to motor learning after the stress experiment as well as neural changes due to stress through an implanted cranial window using 2-photon in vivo imaging.

Chronic stress reduced social interaction and nest building. In addition, some individual mice reduced their preference for sucrose after stress. Mice were determined to be susceptible (54%) or resilient (46%) to stress.

Learning curves of stressed mice differed from controls, in which stress-susceptible mice failed to stay on a rotarod wheel more than controls (P <.001) and resilient mice were better than controls at learning how to stay on the wheel (P <.01).

At 24 hours after the stress experiment, both the resilient (P <.05) and susceptible (P <.01) mice had higher plasma corticosterone levels. Fecal corticosterone levels were higher among the resilient mice (P <.05) and lower for the susceptible mice (P <.01) compared with controls.

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Stress was found to profoundly alter spine densities. At 2 days after the stress experiment, the resilient (90.74%±2.95%) and susceptible (82.87%±3.37%) mice had decreased spinal densities compared with controls (104.91%±3.99%).

In an analysis of neuroplasticity and neuroinflammation, compared with controls, susceptible mice, but not resilient mice, had a lower ramification index, total tree length, spanned area per cell, and area per cell (all P <.05). Colocalization of green fluorescent protein-positive dendrites and ionized calcium binding adaptor molecule 1-positive microglia were increased in susceptible mice (P <.05) but not resilient mice compared with controls.

A proteomics analysis found 52 differentially expressed genes between susceptible mice and controls, 45 between resistant mice and controls, and 100 between susceptible and resistant mice. These proteins were significantly linked with Alzheimer disease (P =2.8×10-9), Parkinson disease (P =4.8×10-6), and Huntington disease (P =4.8×10-6).

These findings may not be generalizable to humans.

The study authors concluded, “Our findings are in line with the understanding of chronic social defeat stress as a robust model of affective neuropsychiatric disorders and inductor of neurodegeneration and glial activation. Here we demonstrate that chronic social stress affects strongly the motor cortex and its function.”

Reference

Gellner AK, Sitter A, Rackiewicz R, et al. Stress vulnerability shapes disruption of motor cortical neuroplasticity.Transl Psychiatry. 2022;12(1):91. doi:10.1038/s41398-022-01855-8