Stereological sampling-based estimates of dopaminergic and cholinergic neuron numbers in young adult and aged male and female Fischer 344 × Brown Norway F1 hybrid rats.

Age is the primary risk factor for neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease, which are characterized by profound loss of midbrain dopaminergic neurons and basal forebrain cholinergic neurons, respectively. In addition, loss of these neurons can occur even in "normal" (i.e., non-pathological) aging, and as a result there is growing recognition of the value of aged animals in studying both normal aging and age-related neurodegenerative disease. The Fischer 344 x Brown Norway F1 hybrid (FBN) rat is commonly used for such purposes and is recommended for use in aging studies by the NIH due to its extended lifespan and more accurate representation of age-related human diseases such as sarcopenia and cognitive decline. Despite the significant value and broad use of this model, dopaminergic and cholinergic neurons have not been well characterized in this strain, and there have been even fewer comparisons between males and females. To address this issue, we used systematic random sampling principles to generate population estimates for dopaminergic neurons in the substantia nigra pars compacta and ventral tegmental area, and cholinergic neurons in the medial septum and vertical limb of the diagonal band of Broca in 5-6.5-month and 20-26-month-old FBN rats of both sexes. Dopaminergic and cholinergic cell bodies were immunolabeled for tyrosine hydroxylase and choline acetyltransferase, respectively. Because the final counts were obtained from full-thickness image stacks using cell-profile inclusion rules and relatively sparse section sampling, these values are presented as stereological sampling-based estimates rather than strict design-based stereological totals. Within these methodological limits, no age differences in dopaminergic or cholinergic neuron-number estimates were detected in any region assessed, nor were there differences between males and females. These data suggest that FBN rats can be used to model induced age-related neurodegenerative disease without the potential confound of a large independent age-associated loss of these dopaminergic or cholinergic neuronal populations.