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Dissection of Hippocampal Dentate Gyrus from Adult Mouse
Published on: November 17, 2009
Anterior hippocampal volume is reduced in behaviorally depressed female cynomolgus macaques
Stephanie L Willard1, David P Friedman, Craig K Henkel
1Interdisciplinary Graduate Program in Neuroscience, Wake Forest University School of Medicine, United States.
Insights
Depression in female macaques is linked to a smaller anterior hippocampus (HC), an area involved in emotion. This finding suggests anterior HC volume reduction may contribute to depressive behavior.
Area of Science:
- Neuroscience
- Comparative Psychology
- Primate Models
Background:
- Hippocampal (HC) volume reduction is observed in human depression, but findings are inconsistent.
- Functional differentiation exists within the HC, with anterior regions linked to emotion and posterior regions to memory.
- Whole HC volume measurements may obscure region-specific changes relevant to depression.
Purpose of the Study:
- To investigate regional hippocampal volume differences in female cynomolgus macaques exhibiting depressive behavior.
- To determine if anterior or posterior HC volumes are specifically associated with a depressive phenotype.
Main Methods:
- Unbiased stereology was used to measure whole, anterior, and posterior HC volumes in 12 adult female cynomolgus macaques.
- Subjects were categorized as depressed (spontaneous depressive behavior) or nondepressed, matched for key physiological and social variables.
- Postmortem HC tissue was sectioned, stained, and analyzed using Neurolucida software for 3D volume reconstruction.
Main Results:
- No significant differences in whole or posterior HC volume were found between depressed and nondepressed macaques.
- A significant 15.4% reduction in anterior HC volume was observed in depressed compared to nondepressed monkeys.
- Average whole HC volume was 4% smaller in depressed macaques, though not statistically significant.
Conclusions:
- Reduced anterior HC volume is associated with a depressive phenotype in female cynomolgus macaques.
- These findings highlight the anterior HC's role in emotional regulation and its potential involvement in depression pathophysiology.
- Regional HC analysis is crucial for understanding the neurobiological underpinnings of depression.
Abstract:
Hippocampal (HC) function and morphology have been implicated in the pathophysiology of depression. Reduced HC volume has been observed in depressed humans, although the effect is not always significant. Studies of functional differentiation of the HC have revealed that the anterior portion is associated with emotional and anxiety-related functioning, and the posterior portion with memory processing. As such, measuring whole HC volume may mask differences seen only in the anterior or posterior HC. We used unbiased stereology to measure whole, anterior, and posterior HC volumes in 12 adult female cynomolgus macaques, half of which exhibited spontaneously occurring depressive behavior defined as a slumped/collapsed body posture with open eyes, and a relative lack of responsivity to environmental stimuli. The two groups were otherwise matched on circulating estradiol, progesterone, and cortisol levels, social status, estimated age, and body weight. Frozen postmortem HC tissue from depressed and nondepressed monkeys was serially sectioned and thionin-stained. According to established neuroanatomical guidelines and with the aid of Neurolucida software (MBF Bioscience), every 10th section throughout the extent of the HC was manually traced and used to reconstruct the 3D models used to determine volumes. Anterior and posterior HC were delineated by the presence or absence of the uncus. No significant differences were found between depressed and nondepressed monkeys for whole or posterior HC volume, although the average HC volume was 4% smaller in depressed than nondepressed monkeys. Anterior HC volumes were significantly smaller (15.4%) in depressed compared to nondepressed monkeys. These results indicate that reduced volume in the anterior HC, an area previously implicated in emotional functioning, may be associated with a depressive phenotype in female cynomolgus macaques.
