5,7-Dihydroxytryptamine induced changes in the postnatal development of central 5-hydroxytryptamine neurons. 1975

C Sachs, and G Jonsson

Systemic administration of the neurotoxic compound 5,7-dihydroxytryptamine (5,7-HT) to newborn rats led acutely (within 1--2 h) to a marked reduction of the in vitro uptake of [3H]5-hydroxytryptamine (5-HT) in homogenates from the cerebral cortex (75% decrease) and the pons-medulla (60% decrease). When 5,7-HT was administered postnatally we found that between days 5 an7 resistance developed in the cerebral cortex towards the 5,7-HT induced reduction in 3H-5-HT uptake. This was most likely the result of the postnatal development of the blood-brain barrier. These results show that 5,7-HT can pass the blood-brain barrier in the neonate stage and enter the brain to exert its well-known neurotoxic action on 5-HT neurons. The [3H]5-HT uptake in the cerebral cortex was reduced quantitatively to the same extent up to the 28th postnatal day, after which time a moderate recovery took place. Endogenous 5-HT was reduced by 40% in the cerebral cortex when measured in adult animals. In the pons-medulla there was a rapid recovery of the [3H]5-HT uptake during the first week after the 5,7-HT treatment and on the 14th postnatal day the increase was as much as 75% compared with the control. Endogenous 5-HT and [3H]5-HT uptake was increased by 40--50% when the analysis was performed 2 months after the 5,7-HT treatment. Studies of [3H]noradrenaline (NA) uptake after 5,7-HT administration at birth showed that this treatment similarly affected the NA neurons, though to a lesser extent. The effects on the NA neurons could be abolished by pretreatment with the "membrane pump" blocker desipramine, leaving the action of 5,7-HT on 5-HT neurons almost unaffected. Analysis of the [3H]5-HT uptake kinetics in the pons-medulla showed that the 5,7-HT treatment did not affect the Km while the Vmax was increased. It is concluded that neonatal 5,7-HT treatment produces a marked 5-HT denervation of the cerebral cortex, while there is a stimulated postnatal outgrowth of 5-HT nerve terminals in the pons-medulla, after an initial partial damage of the neurons.

UI MeSH Term Description Entries
D007279 Injections, Subcutaneous Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin. Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D008297 Male Males
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D011149 Pons The front part of the hindbrain (RHOMBENCEPHALON) that lies between the MEDULLA and the midbrain (MESENCEPHALON) ventral to the cerebellum. It is composed of two parts, the dorsal and the ventral. The pons serves as a relay station for neural pathways between the CEREBELLUM to the CEREBRUM. Pons Varolii,Ponte,Pons Varolius,Pontes,Varolii, Pons,Varolius, Pons
D001812 Blood-Brain Barrier Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue. Brain-Blood Barrier,Hemato-Encephalic Barrier,Barrier, Blood-Brain,Barrier, Brain-Blood,Barrier, Hemato-Encephalic,Barriers, Blood-Brain,Barriers, Brain-Blood,Barriers, Hemato-Encephalic,Blood Brain Barrier,Blood-Brain Barriers,Brain Blood Barrier,Brain-Blood Barriers,Hemato Encephalic Barrier,Hemato-Encephalic Barriers
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D003864 Depression, Chemical The decrease in a measurable parameter of a PHYSIOLOGICAL PROCESS, including cellular, microbial, and plant; immunological, cardiovascular, respiratory, reproductive, urinary, digestive, neural, musculoskeletal, ocular, and skin physiological processes; or METABOLIC PROCESS, including enzymatic and other pharmacological processes, by a drug or other chemical. Chemical Depression,Chemical Depressions,Depressions, Chemical
D005260 Female Females
D000375 Aging The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time. Senescence,Aging, Biological,Biological Aging

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