Changes in vasopressin neurons and fibers in aging and Alzheimer's disease: reversibility in the rat.

The neuropeptide vasopressin (VP) is released from the neurohypophysis into the circulation where it acts as antidiuretic hormone on the kidney. In addition, VP is present in nerve cells and fibers in several areas in the rodent and primate brain where it acts as a neurotransmitter or neuromodulator. In the human brain a marked decrease in total cell number and VP cell number was observed in senescence in the suprachiasmatic nucleus, the hypothalamic nucleus regulating circadian rhythms. This degeneration was even more pronounced in Alzheimer's disease (AD) and might be related to the disturbances in sleep-wake cycle and endocrine rhythms which occur in this condition. No degenerative changes were observed with aging or in AD in the human hypothalamo-neurohypophyseal system (HNS); on the contrary, total cell numbers remain unaltered and the VP cells in this system are activated in senescence, probably in compensation for decreased sensitivity of the kidney to VP. It is proposed that this activation may prevent degeneration of the VP cells in the HNS. The extrahypothalamic VP innervation in the male rat brain was shown to be diminished in senescence in a number of areas. This innervation, which was previously shown to depend on plasma levels of sex-steroids, could be restored in a number of brain structures by subcutaneous testosterone administration to senescent male rats for one month. Reversibility of changes in VP innervation in the senescent rat brain through peripheral testosterone supplementation might open new possibilities for the development of therapeutic strategies in age-related disorders of the central nervous system.