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The correlation between high testosterone and high zinc levels is apparent in many studies ( 15 ) ( 16 ) ( 17 )( 18 ) ( 19 ) ( 20 ), yet other studies have not found such a correlation. Another paper, by Sjöström et al., also found no significant association between low testosterone and zinc ( 21 ), and most previous reports using zinc supplements ( 22 ) or zinc-deficient animals ( 23 ) do not find such a correlation.The role of testosterone in the growth of the brain has received a great deal of attention in recent years. Some of these studies are relevant to the present paper. Hwang and coworkers examined testosterone and zinc uptake by rat brain slices ( 2 ); the uptake of zinc, which had a more pronounced effect on growth, was less pronounced in the male animals, compared with the females. Similarly, in mice, testosterone stimulates growth of the brain by promoting both neuronal size and dendritic extension. It also inhibits neuronal apoptosis by inhibiting the cytochrome oxidase inhibitor p53, which results in apoptosis and neurodegeneration in animal models of Alzheimer's disease ( 24 ).Zinc is necessary for proper cell-to-cell communication and can facilitate neuronal repair ( 24 ). It is a critical mineral for normal brain development and function and thus an essential part of brain tissue. Chronic zinc deficiency causes significant brain atrophy and cognitive decline ( 25 ). Chronic zinc deficiency also decreases levels of neurotransmitters and plays a central role in inflammation and in neurotoxicity. It is believed that zinc plays a critical role in the synapse, which is an area of the brain in which cell communication is achieved through the interaction of nerve cells ( 26 ). Zinc participates extensively in neurotransmitter production and thus helps regulate mood and mood-like behaviors and also in the control of anxiety and stress ( 26 ). Chronic zinc deficiency has been associated with decreased brain growth in both rodents and humans. The clinical and preclinical studies in humans point to the importance of zinc in brain growth ( 12 ) ( 13-15 ). However, it is unclear whether these preclinical observations and animal studies are due to differences in the animals used in research vs. the population examined ( 16 ).The present report has been developed from earlier animal studies utilizing zinc to study the impact of testosterone depletion during adult life on neuronal survival and plasticity. Several mechanisms for the influence of testosterone on survival, synaptic plasticity, neuroprotection, and neurogenesis have been proposed. For example, when testosterone levels are decreased either from the neonatal period to adulthood or in adulthood, it significantly reduces growth of the cortical gray matter, bothRelated Article: