Glial gene expression during aging in rat striatum and in long-term responses to 6-OHDA lesions.
The male rat striatum was examined for age-related changes in mRNAs expressed in astrocytes and microglia in two rat genotypes that differ by 35% in mean and maximum life spans: F344 and the longer-lived F1 (BN x F344) hybrid. The findings extend the established age-related increases in GFAP (glial fibrillary acidic protein) to other glial mRNAs: two lipoprotein mRNAs that are predominantly expressed in striatal astrocytes, apoE (apolipoprotein E) and apoJ (apolipoprotein J, clusterin, CLI, or SGP-2), and two mRNAs expressed in striatal microglia, TGF-beta1 and complement C1qB. By Northern blot hybridization, both genotypes showed progressive increases of GFAP mRNA to > 2.5-fold by the lifespan. Although the rat strains differed 35% in life span, the slope of the GFAP mRNA regression on age did not differ. Relative to GFAP, the increases of apoE, apoJ, C1q, and TGF-beta1 mRNAs were smaller, < or = 1.5-fold. Because prior studies showed that acute damage to striatal afferents induced astrocyte gene expression increases resembling those that also occur during aging, we examined long-term effects of damage to substantia nigra neurons on striatal astrocyte changes during aging. Young F344 rats were given 6-OHDA lesions that cause striatal dopamine deficits and induce GFAP. When examined 15 months later at age 18 months, there was no effect during prior lesions on the age-related elevation of GFAP mRNA. We conclude that aging changes in striatal GFAP mRNAs do not interact with loss of dopaminergic output to the striatum from 6-OHDA lesions and may be independent of the relatively modest dopaminergic losses during normal aging.
Department of Psychiatry, Mt. Sinai School of Medicine, New York, New York 10029-6574, USA. gp2@doc.mssn.edu
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Pasinetti
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Hassler
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Stone
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Finch
D000375:Aging / Q000235:genetics*; D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis; D001253:Astrocytes / Q000502:physiology; D051152:Clusterin; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006023:Glycoproteins / Q000096:biosynthesis; D008297:Male; D018832:Molecular Chaperones; D017072:Neostriatum / Q000254:growth & development* / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009457:Neuroglia / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D016627:Oxidopamine; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D013563:Sympathectomy, Chemical; D013565:Sympatholytics; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D001057:Apolipoproteins E; D051152:Clusterin; D005904:Glial Fibrillary Acidic Protein; D006023:Glycoproteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D013565:Sympatholytics; D016212:Transforming Growth Factor beta; D016627:Oxidopamine