Age-induced changes in single locus coeruleus brain transplants grown in oculo: an in vivo electrochemical study.
Brain stem tissue from fetal Sprague-Dawley rats containing the nucleus locus coeruleus (LC) was transplanted into the anterior chamber of the eye of young adult host rats and was studied at 4-6 months (young control) or 24-28 months after grafting (old). High-speed in vivo electrochemical measurements were used to characterize the potassium-evoked synaptic overflow of norepinephrine (NE) in both young and aged LC brain grafts. The amplitudes of potassium-evoked NE overflow were attenuated in the aged grafts as compared to the young LC grafts. In addition, the rise times of potassium-evoked responses were longer in the old LC grafts than in the young transplants. In contrast, the NE content of aged LC grafts, as determined by high-performance liquid chromatography coupled with electrochemical detection (HPLC-EC), was only slightly diminished and not significantly different from the NE levels seen in young LC grafts. However, light microscopical evaluation using tyrosine-hydroxylase immunocytochemistry revealed pyknotic cell bodies and fluorescent accumulations in aged locus coeruleus transplants which were indicative of degeneration in these grafts. The present data demonstrate a significant age-related decline in the presynaptic function of NE-containing neurons in intraocular locus coeruleus transplants of Sprague-Dawley rats.
Department of Psychiatry, University of Colorado Health Sciences Center, Denver 80262.
G A
GA
Gerhardt
M R
MR
Palmer
A C
AC
Granholm
D000375:Aging / Q000502:physiology*; D000818:Animals; D001933:Brain Stem / Q000637:transplantation; D016380:Brain Tissue Transplantation / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D004594:Electrophysiology; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000378:metabolism / Q000637:transplantation*; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D009799:Ocular Physiological Phenomena; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine