Expression and function of astrocytic gap junctions in aging

Astrocytic gap junctions have been implicated in a variety of signaling pat hways essential to normal brain function. However, no information exists on the prevalence of gap junction channels and their function in the aging br ain. Here we have compared the expression of the two most abundant astrocyt ic gap junction proteins in young and senescent brains and quantified the e xtent of functional gap junction coupling. The expression level of Cx43 pea ked in 7-month-old mice. The relative numbers of Cx43 immunoreactive plaque s were 596+/-61, 734+/-62, and 755+/-114 in 3-, 7-, and 21-month-old mice, whereas plaques size averaged 0.9+/-0.1 mum(2) (3 months), 1.3+/-0.1 mum(2) (7 months), and 0.7+/-0.1 mum(2) (21 months). The expression level of Cx30 was also highest in 7-month-old animals (315+/-49 plaques, size 0.8+/-0.07 mum(2) vs 585+/-51 plaques, size 0.9+/-0.1 mum(2) in 3- and 7-month-old mi ce, respectively), but only 262+/-63 plaques (size 0.4+/-0.04 mum(2)) in 21 -month-old mice. Western blot analysis revealed that the content of both Cx 43 and Cx30 remained relatively constant at 3, 7, and 21 months. The fluore scence recovery of photobleach technique (FRAP) was used to evaluate coupli ng in freshly prepared hippocampal slices. Gap junction coupling did not ch ange significantly as a function of aging, but a tendency towards reduced c oupling was observed as the animals aged. Average fluorescence recovery aft er 2 min was 63+/-6% in younger animals, 59+/-5% in adult animals, and 54+/ -4% in old brain. These observations indicate that although astrocytic gap junction proteins are maintained at high levels through the entire lifespan of mice, aging is associated with changes in the number and size of both C x30 and Cx43 gap junction plaques. (C) 2001 Elsevier Science B.V. All right s reserved.