Effects of neonatal administrations of 6-OHDA on brain development. II. Changes in the central noradrenaline system.

Abstract

Following subcutaneous injections of 6-OHDA into neonatal rats, the central noradrenaline (NA) system was examined by fluorescence and electron microscopy from 14 to 42 days after birth. Repeated administrations of 6-OHDA induced a serious confusion in the distribution of the central amines. NA fluorescence was reduced in the neurons of the main part of the locus ceruleus, while a considerably strong fluorescence remained in the neurons of the ventral part of the nucleus and the subceruleus. Coarse varicosities markedly increased in number in the pons and cerebellum, particularly in the motor nucleus of the trigeminal nerve, where they surrounded individual motor neurons. On the contrary, a depletion of NA was obvious in the entire cerebral cortex, even though a few fluorescence varicosities were occasionally seen in the entorhinalis and piriformis.Exemplifying ultrastructural alterations in the pons after 6-OHDA administrations, small cored vesicles and large ones were demonstrated in the terminals adjacent to the trigeminal motor neurons by means of potassium permanganate fixation, but they were relatively few. Besides, it was characteristic of the synaptic cleft of the axo-somatic synapses to be so extended as to double its usual width. Occasionally, deposits of a dense material were seen in the loosened gap and glial processes invaded among the terminals contacting to the motor neurons. Thus, the increased NA around the motor neurons was probably accumulated as a soluble substance in the extravesicular compartments.The cerebral cortex showing a chronic reduction of NA fluorescence after 6-OHDA administrations revealed an occurrence of neuronal necrosis. Necrotic neurons accompanied with the membranous lemellar bodies (MLB) were mainly scattered in the deeper layers of the cingulate cortex and the entorhinalis, though some were seen in the superficial layers of the temporal cortex. It seemed that the membrane structure of the MLB located in the terminals and the glial processes initially arose from the subsurface cisterns in the adjacent necrotic neuron. These alterations in the cerebral cortex were somewhat similar to those observed in the nigro-neostriatal dopamine system, suggesting again that amine input may be important to maintain the normal function of the cortical neurons.