Increased Neuronal Nuclear and Perikaryal Size in the Medial Mamillary Nucleus of Vascular Dementia and Alzheimer’s Disease Patients: Relation to Nuclear Estrogen Receptor α

Background: The hypothalamic medial mamillary (MMN) and the tuberomamillary (TMN) nuclei are important hubs in memory circuits. Previous studies determining the neuronal Golgi complex size showed decreased metabolic activity of the TMN neurons in both Alzhei­mer’s disease (AD) and vascular dementia (VD), and no obvious decline in the MMN of these patients. Objectives: In the present study, we aimed at determining whether other morphometric parameters that are informative about the neuronal metabolic activity are changed in the MMN of AD and VD patients and whether they can be related to the expression of the nuclear estrogen receptor α (ERα) that can mediate neurotrophic effects of estrogens in the brain. Method: The size of neuronal nuclei and perikarya was determined in AD, VD, and nondemented control patients, in relation to the expression of the nuclear ERα. Results: We found that neuronal nuclear and perikaryal sizes were significantly larger in the MMN in VD than in control patients (p < 0.01). Neuronal nuclei (p < 0.05), but not perikarya were larger in AD than in control patients. Neuronal nuclei and perikarya were larger if nuclear ERα staining was present. The intensity of ERα in the neuronal nuclei was significantly correlated with both nuclear and perikaryal sizes (p < 0.007). Conclusions: The human MMN shows a remarkable activation in aging and extra activation in dementias (AD and VD) that may be mediated by nuclear ERα. This makes it so far a unique brain area to study compensatory mechanisms that may prevent neurodegeneration.