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Filling in the gap: Hippocampal CA1 neuronal counts and volumes in female cognitive controls
Erin-Marie C Smith1, Anne M Alexander1, Kaitlyn H Watt1
1Athinoula A. Martinos Center for Biomedical Imaging, Radiology, Massachusetts General Hospital, 149 13(th) St, Boston, MA 02129, USA.
Insights
This study provides baseline data on CA1 neuron counts in male and female brains, finding no significant sex differences. This suggests CA1 neuron count does not explain why females are more vulnerable to Alzheimer's disease.
Area of Science:
- Neuroscience
- Stereology
- Human Brain Anatomy
Background:
- The CA1 subfield of the human hippocampus is vulnerable to hypoxia.
- Previous studies on CA1 neuron counts and size have predominantly used male samples, underrepresenting females.
- Baseline data for female CA1 neuron counts and size are lacking.
Purpose of the Study:
- To provide comprehensive baseline data on CA1 total neuron count and mean neuron volume in both male and female human brains.
- To investigate potential associations between CA1 neuron characteristics and factors such as age, sex, hemisphere, and p-tau pathology.
- To address the underrepresentation of female samples in previous stereological studies of the hippocampus.
Main Methods:
- Utilized optimal stereology methods, including the optical fractionator and nucleator probes, for neuron counting and volume estimation.
- Analyzed 22 human brain hemispheres (11 female, 11 male) from both hemispheres.
- Measured hippocampal volume using 1 mm isotropic ex vivo MRI in a subset of 20 samples.
Main Results:
- The average CA1 total neuron count was 5.01 × 10^6 ± 1.77 × 10^6 neurons.
- The average CA1 neuron volume was 4461.9 ± 767.1 μm^3.
- A positive correlation was observed between total neuron count and hippocampal volume, consistent with prior research.
- No significant associations were found between age, sex, hemisphere, or mild p-tau pathology and CA1 neuron count or volume.
Conclusions:
- Cognitively intact males and females exhibit similar CA1 total neuron counts and mean neuron volumes.
- CA1 total neuron count does not appear to be a significant factor in the increased vulnerability of females to Alzheimer's disease.
- This study establishes crucial baseline data for future research on hippocampal neuroanatomy and neurological disorders.
Abstract:
CA1 is a subfield in the human hippocampus that is particularly vulnerable to hypoxia. Previous stereological studies on CA1 have examined primarily male samples, leaving female total neuron counts not represented or underrepresented in total neuron count and neuron size studies. Our study sought to fill in the gap and provide baseline data on an equal number of male and female brains, representing both hemispheres with optimal stereology methods. Twenty-two human brain hemispheres, 11 females, 11 males (9 right hemispheres, 13 left hemispheres), were counted using the optical fractionator and nucleator probes for total neuron count and mean neuron volumes. Hippocampal volume was measured in a subset of 20 samples from 1 mm isotropic ex vivo MRI. The CA1 total neuron count across all samples was 5.01 × 106 ± 1.77 × 106 (median ± interquartile range) neurons. The CA1 neuron volume across all samples was 4461.9 ± 767.1 μm3 (median ± interquartile range). Total neuron count was shown to positively correlate with hippocampal volume measured from ex vivo MRI, validating previous studies. There was insufficient evidence of associations between age, sex, hemisphere, or p-tau pathology in hippocampus (isolated to mild) and total neuron count, mean neuron volume, and area. This may suggest that cognitively intact males and females have similar total neuron counts and mean neuron volumes. This implies that CA1 total neuron count is not significantly contributing to the increased vulnerability of females to Alzheimer's disease.
