Deficits in cognitive flexibility induced by chronic unpredictable stress are associated with impaired glutamate neurotransmission in the rat medial prefrontal cortex

AbstractPrevious postmortem and animal studies have shown decreases in the prefrontal cortex (PFC) volume and the number of glial cells in the PFC of depression. Running exercise has been shown to alleviate depressive symptoms. However, the effects of running exercise on the medial prefrontal cortex (mPFC) volume and oligodendrocytes in the mPFC of depressed patients and animals have not been investigated. To address these issues, adult male rats were subjected to chronic unpredictable stress (CUS) for 5 weeks, followed by treadmill running for 6 weeks. Then, the mPFC volume and the mPFC oligodendrocytes were investigated using stereology, immunohistochemistry, immunofluorescence and western blotting. Using a CUS paradigm that allowed for the analysis of anhedonia, we found that running exercise alleviated the deficits in sucrose preference, as well as the decrease in the mPFC volume. Meanwhile, we found that running exercise significantly increased the number of CNPase+ oligodendrocytes and Olig2+ oligodendrocytes, reduced the ratio between Olig2+/NG2+ oligodendrocytes and Olig2+ oligodendrocytes and increased myelin basic protein (MBP), CNPase and Olig2 protein expression in the mPFC of the CUS rat model. However, running exercise did not change NG2+ oligodendrocyte number in the mPFC in these rats. These results indicated that running exercise promoted the differentiation of oligodendrocytes and myelin-forming ability in the mPFC in the context of depression. These findings suggest that the beneficial effects of running exercise on mPFC volume and oligodendrocytes in mPFC might be an important structural basis for the antidepressant effects of running exercise.

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Sexual experience enhances cognitive flexibility and dendritic spine density in the medial prefrontal cortex

Neurobiology of Learning and Memory ◽

10.1016/j.nlm.2015.07.007 ◽

2015 ◽

Vol 125 ◽

pp. 73-79 ◽

Cited By ~ 16

Author(s):

Erica R. Glasper ◽

Elizabeth A. LaMarca ◽

Miriam E. Bocarsly ◽

Maria Fasolino ◽

Maya Opendak ◽

...

Keyword(s):

Prefrontal Cortex ◽

Medial Prefrontal Cortex ◽

Cognitive Flexibility ◽

Dendritic Spine ◽

Sexual Experience ◽

Spine Density ◽

Dendritic Spine Density

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Exposure to the Synthetic Progestin, 17α-Hydroxyprogesterone Caproate During Development Impairs Cognitive Flexibility in Adulthood

Endocrinology ◽

10.1210/en.2015-1775 ◽

2016 ◽

Vol 157 (1) ◽

pp. 77-82 ◽

Cited By ~ 17

Author(s):

Jari Willing ◽

Christine K. Wagner

Keyword(s):

Prefrontal Cortex ◽

Progesterone Receptor ◽

Medial Prefrontal Cortex ◽

Cognitive Flexibility ◽

Neural Circuit ◽

Developing Brain ◽

Premature Delivery ◽

Cognitive Behaviors ◽

Hydroxyprogesterone Caproate ◽

Cell Layers

Abstract The synthetic progestin, 17α-hydroxyprogesterone caproate, is increasingly used for the prevention of premature birth in at-risk women, despite little understanding of the potential effects on the developing brain. Rodent models suggest that many regions of the developing brain are sensitive to progestins, including the mesocortical dopamine pathway, a neural circuit important for complex cognitive behaviors later in life. Nuclear progesterone receptor is expressed during perinatal development in dopaminergic cells of the ventral tegmental area that project to the medial prefrontal cortex. Progesterone receptor is also expressed in the subplate and in pyramidal cell layers II/III of medial prefrontal cortex during periods of dopaminergic synaptogenesis. In the present study, exposure to 17α-hydroxyprogesterone caproate during development of the mesocortical dopamine pathway in rats altered dopaminergic innervation of the prelimbic prefrontal cortex and impaired cognitive flexibility with increased perseveration later in life, perhaps to a greater extent in males. These studies provide evidence for developmental neurobehavioral effects of a drug in widespread clinical use and highlight the need for a reevaluation of the benefits and potential outcomes of prophylactic progestin administration for the prevention of premature delivery.

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