Selective Neuron Loss in the Dorsal Prefrontal Cortex During Normal Aging
Stranahan AM, Jiam NT, Spiegel AM, Gallagher M. Aging reduces total neuron number in the dorsal component of the rodent prefrontal cortex. J Comp Neurol 2012;520(6):1318-1326. doi: 10.1002/cne.22790.
Background: Previous research suggested that aging is associated with widespread neuronal loss, but later stereological analyses revealed that many cortical and hippocampal regions maintain stable neuron numbers during normal aging. However, focal neuronal loss has been observed in the prefrontal cortex (PFC) of primates, leaving it unclear whether similar changes occur in rodents. Given the functional and anatomical parallels between rodent and primate PFC, this study investigated whether neuron loss accompanies aging in the rat prefrontal cortex.
Hypothesis: This study hypothesized that normal aging leads to a reduction in total neuron number, including inhibitory interneurons, within the dorsal component of the rat prefrontal cortex.
Methods: The authors analyzed brain tissue from young (6 months) and aged (24 months) male rats. Unbiased stereological estimates of total neuron and GAD67-positive cell numbers were obtained using the Optical Fractionator technique implemented in Stereo Investigator. Cresyl violet staining identified principal neurons, and immunohistochemistry for GAD67 labeled inhibitory interneurons. Volume estimates were calculated with the Cavalieri method, and statistical analyses were performed to compare neuronal counts between age groups.
Results: Aged rats exhibited significant reductions in both total neuron number and GAD67-positive interneurons within the dorsal prefrontal cortex, without corresponding volume loss. No age-related changes occurred in the ventral prefrontal cortex. Neuronal reductions were independent of hippocampus-dependent spatial memory performance.
Conclusions: The findings demonstrate that aging selectively decreases neuronal populations in the dorsal prefrontal cortex of rats, indicating that focal cortical vulnerability to aging is conserved across species.
