Sex- and Age-Related P75 Neurotrophin Receptor Expression in the Human Supraoptic Nucleus

Abstract

The human supraoptic nucleus (SON) is the main production site of plasma vasopressin. Previously, using the Golgi apparatus and cell size as measures for neuronal metabolic activity, an activation of vasopressinergic neurons was found during ageing in the human SON in women but not in men. We hypothesized that the low-affinity neurotrophin receptor p75 (p75^NTR) might be involved in the mechanism of activation of vasopressin neurons in postmenopausal women, since this receptor was found to be expressed in the SON neurons of aged individuals, and because p75^NTR expression was shown to be suppressed by estrogens. Therefore, we investigated whether p75^NTR immunoreactivity in the SON neurons was age- and sex-dependent. For this purpose, we studied paraffin sections of the SON in 32 postmortem brains of control patients ranging in age from 29 to 94 years with an anti-p75^NTR antibody and determined the area of p75^NTR immunoreactivity per neuron using an image analysis system. To study whether the p75^NTR might also participate in the activation of SON neurons, we related Golgi apparatus size to the area of p75^NTR immunoreactivity per cell in the same patients. We found that the area of p75^NTR immunoreactivity per cell correlated indeed significantly with age and with Golgi apparatus size only in women but not in men. Therefore, our results suggest that p75^NTR is involved in postmenopausal activation of vasopressinergic neurons in the human SON.

The Role of Hypothalamus and Endocrine System in Sexuality.

“…P75 NTR immunoreactivity indeed correlated significantly with age and with Golgi-apparatus size, but only in women, not in men. These observations suggest that p75 NTR modulates the effects of estrogens on vasopressinergic neurons in the human SON (Ishunina, Salehi, & Swaab, 2000).…”

“…The activation of neurosecretory vasopressin neurons in postmenopausal women was confirmed by in situ hybridization (Ishunina, Salehi, & Swaab, 2000) and by measuring the cell size as a parameter for neuronal activity. The vasopressin neurons in the SON and PVN appeared to be larger in young men than in young women.…”

Ageing restructures the transcriptome of the hypothalamic supraoptic nucleus and alters the response to dehydration

“…Although we have previously employed microarrays to catalogue and compare differences in the transcriptomic response to dehydration of adult male and female SON 39 , in this ageing study, we only examined male rats. Given that age-related sex differences in osmoregulation in the rat have been described 78 , 79 , this is a shortcoming of this study. In this context, it is important to note that in young humans, both sexes have the same number of AVP neurones 80 , but these neurones are larger in males compared to females 81 .…”

Ageing restructures the basal transcriptome of the core hypothalamic osmoregulatory control centre and alters the response to dehydration

“…Although we have previously employed microarrays to catalogue and compare differences in the transcriptomic response to dehydration of adult male and female SON (39), in this ageing study we only examined male rats. Given that age-related sex differences in osmoregulation in the rat have been described (75,76) this is a shortcoming of this study. In this context it is important to note that in young humans, both sexes have the same number of AVP neurones (77), but these neurones are larger in males compared to females (78).…”