Blues Clues: An Analysis of Neuronal and Glial
Cell Number in the Orbitofrontal Region of the Prefrontal
Cortex in Relation to Mood Disorders
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Rachel Torrey |
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Depression affects more than 19 million American adults a year--nearly 10% of the US population over the age of 18. It is the most common serious brain ailment, yet little is known about the neurobiology of this neuropsychiatric illness. However, recent studies have revealed structural and functional changes in the brains of people suffering from major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia, a brain disease related to depression. MDD is characterized by a loss of interest in activities, sad and depressed feelings, thoughts of death or suicide, and changes in patterns of eating and sleeping. BD is characterized by extreme changes in mood, behavior, and energy levels, with alternate stages of mania and depression. Schizophrenia is characterized by thought disturbances, depressed feelings, delusions, and hallucinations. These disorders have been associated with physical and chemical changes within the brain.
A recent study has shown that a low glial cell count and a low glial-to-neuron ratio in a specific region of the prefrontal cortex (PFC) of the brain may be associated with depression. The PFC receives highly processed sensory information and is associated with high-level cognitive and emotional processes. Glial cells act as the support system of the nervous system and assist in the functional activity of neurons. Glial cells provide nutrients to neurons and may be associated with the re-cycling of neurotransmitters. A low glial cell count in the PFC may be related to depression because too few glial cells are available to provide proper support to the neurons and neurotransmitter activity of this emotional-control area of the brain.
By analyzing different regions of the PFC for a low glial cell count in cases of both MDD and BD, we searched for further evidence of a physical brain abnormality associated with depression. A part of the orbitofrontal region of the PFC was analyzed to observe the glial cell-to-neuron ratio and the overall glial cell count. This region of the PFC, known as area 13m, is defined on architectonic ground, but generally occupies the lateral bank of the olfactory sulcus and part of the medial orbital gyrus. The orbitofrontal region was delineated by Dr. Price on 36 different brains that were provided by the Stanley Foundation brain bank. Ten different brains from three different groups were analyzed: control samples, MDD samples, and BD samples. Six schizophrenic brains were also examined. Five slides of each brain sample were analyzed, and on each slide 10 fields were examined for glial cells and neurons. A low glial cell count in the BD and MDD samples would give further evidence that a low glial cell count in regions of the PFC indicates depression.
In a double blind experiment following stereology procedures, a microscope, microcator, and a personal computer equipped with a CAST grid system were used to analyze the brain samples. Cell numbers, area, and volumes were estimated using the optical dissector method, which eliminates double counting. Using random sampling at a magnification of 100x, an average of 10 fields was counted in each slide, resulting in an average of 50 fields in each brain. Neurons were distinguished by their larger size, none spherical shape, stained cytoplasm, and nucleolus. Glial cells were small, round, and had no stained cytoplasm. The numbers of cells counted was recorded. Three different quantities were measured in this experiment: the glial cells-to-neuron ratio, the glial cell density (the number of glial cells counted in a volume), and the total number of glial cells within area 13m. These quantities were used to analyze brain tissue to relate cell count to the likelihood of depression.
I did not observe a significant difference in the glial cell count and the glial cell-to-neuron ratio in the brain samples of the orbitofrontal region of the PFC. There was little variation in the control, BD, MDD, and schizophrenic samples in relation to cell count. These findings could be used as negative evidence that glial cell-to-neuron ratio may only indicate depression within specific regions of the PFC.
I would like to thank Dr. Joseph Price for his support and assistance throughout my research.
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