Neuroplasticity in the Human Hypothalamus During Ageing

ABSTRACT

The various cell groups in the human hypothalamus show different patterns of ageing, which are the basis for changes in biological rhythms, hormone production, immune processes, autonomic functions and behavior. The suprachiasmatic nucleus (SCN), the clock of the brain, exhibits circadian and seasonal rhythms in peptide synthesis that are disrupted later in life. Furthermore, the age-related sexual differences in the number of vasoactive intestinal polypeptide neurons in this nucleus reinforces the idea that the SCN is not only involved in the timing of circadian rhythms but also in the temporal organization of reproductive functions. The sexually dimorphic nucleus of the preoptic area (SDN-POA), or intermediate nucleus, is twice as large in men as in women, a difference that arises between the ages of 2–4 years and puberty. During ageing a dramatic, sex-dependent decrease in cell number occurs, leading to values which are only 10–15% of the cell number found in early childhood. The vasopressin and oxytocin producing cells in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) are examples of neuron populations that seem to stay perfectly intact in old age. The synthesis of vasopressin in the SON is even increased in elderly women and remains stable in elderly men. Other examples of neuronal activation during ageing are found in the parvocellular corticotropin-releasing-hormone (CRH) containing neurons in the PVN, as indicated by the increase in the number of CRH expressing neurons and by their co-expression of vasopressin. The nucleus basalis of Meynert (NMB), a major source of cholinergic innervation to the neocortex, shows a progressive degeneration of cholinergic neurons in the course of ageing, along with a decreased neuronal metabolic activity, severe cytoskeletal alterations and a loss of high and low affinity neuroptrophin receptors. On the other hand, the protein synthetic activity of the ventromedial nucleus (VMN), a hypothalamic area involved the organization of sex-specific functions and sexual behavior, depends on the age and gender of the subject. The size of the Golgi apparatus (GA) relative to the cell size in the VMN, for example, is larger in young women than in young men and larger in elderly men than in young men. In addition, the GA/cell size ratio is positively correlated with age in men and not in women. The arcuate nucleus of the hypothalamus (ARH), or tubero-infundibular nucleus, contains hypertrophic neurons in postmenopausal women. These hypertrophied neurons contain neurokinin-B, substance P and estrogen receptors and probably act on LHRH neurons as interneurons. The lateral tuberal nucleus (NTL), probably involved in feeding behavior and energy metabolism, does not show any neuronal loss in senescence. To sum up, each cell group of the human hypothalamus has its own sex-specific pattern of ageing. In fact, some hypothalamic nuclei show a dramatic functional decline with ageing, whereas others seem to become more active later in life.