Use of Antisense Oligodeoxynucleotides in the Study of Neuroendocrine Aging

One of the difficulties in the field of the neurobiology of aging is that many of the studies are necessarily correlative in nature. Investigators interested in the neurotransmitter or neuropeptide control of a given brain function often describe the situation in young animals and compare these observations with findings for groups of aged animals. However, ascribing causation with such studies is difficult at best. The use of antisense oligodeoxynucleotides described in this article allows the investigator to target one or more neuropeptides expressed in a confined area of the brain for selective abiation. The assessment of cause and effect on the physiological endpoint of Interest then becomes more tractable. Having previously identified age-related changes in neuropeptide dynamics that may underlie certain aspects of endocrine aging, we used this method to determine whether specific antisense oligodeoxynucleotide treatment of young animals mimicked the effect of age on the endocrine system. The theoretical background and practical aspects of the method are presented in sufficient detail to allow investigators not familiar with the technique to design appropriate oligodeoxynucleotides and use them in their research.