THE EARLY POST‐NATAL DEVELOPMENT OF THE NEURONAL LYSOSOME¹

Abstract

The hydrolysis of p-nitrophenyl-2-acetamido-2-deoxy-fi-~-gluco-(I) and 8-Dgalacto-pyranoside (11) and of p-nitrophenyl-a-D-mannopyranoside (111) by neuronal cell bodies and glial cells isolated from the cerebral cortex of 18-day-old or adult rats was found to be equally efficient, with relative ratios of hydrolysis for I, I1 and I11 of approximately 10: 1 : 0 5 in both cell types and at both ages. Homogenatesoftheneuronal cell bodies obtained from cerebral cortices of 3-, 8-, 12-, 18-and 32-day-old rats were subjected to differential centrifugation and the subcellular localization of N-acetyl-fi-o-ghcosaminidase (EC 3.2.1.30) bydrolysing (I)] was compared to that of the mitochondrial marker, succinate-INToxidoreductase (EC 1.3.99.1). A fraction in which N-acetyl-B-D-ghcosaminidase exhibited maximal specific activity could be isolated at all ages, an observation indicating that the potential for active hydrolytic performance is incorporated into the neuronal lysosome very early post-natally. The specific activities of N-acetyl-fi-D-glucosaminidase and succinate-INT-oxidoreductase reached their respective maxima at widely different times postnatally: at 10-12 days for the mitochondrial enzyme and at about 18 days for the glycosidase, a difference suggesting that in the cortical neuron lysosomes and mitochondria develop out of step. The mitochondrial, lysosomal and microsomal fractions obtained by differential centrifugation were subjected to equilibrium density centrifugation and the presence of two populations of N-acetyl-fi-D-glucosaminidase-bearing particles was demonstrated. Although their presence was readily apparent in the neurons from 8-and 12-day old brains, it was difficult to discern their presence in the neurons from the 3-and the 18-day-old brains. In 8-day-old brains gradient fractions obtained from neurons containing N-acetyl-P-Dglucosaminidase of a specific activity up to %fold higher than that of the enzyme in the original neuronal homogenate were examined by electron microscopy and the concentration of numerous lysosomes and derivative bodies in these fractions was verified. Our present study demonstrates the capability of the immature and developing neuron to tightly couple the pace of its degradative processes to that of its highly efficient and highly selective synthetic activities. acetylaminodeoxyglucohydrolase) is localized in the lysosomes of the cerebral cortex of the rat (SELLINGER, RUCKER and DE BALBIAN VERSTER, 1964) and the guinea pig (BOSMANN and HEMSWORTH, 1970), as well as in the lysosomes of several other anatomical areas of the rat brain (SELLINGER and HIAIT, 1968; SELLINGER and NORDRUM, 1969; SELLINGER, NORDRUM and IDOYAGA-VAKGAS, 1971b). TALLMAN, BRADY and SUZUKI (1971) recently demonstrated the lysosomal localization of this hydrolase in

Intracellular distribution of psychotropic drugs in the grey and white matter of the brain: the role of lysosomal trapping

“…The present results are in agreement with data obtained by other authors who found the highest density of lysosomes in neurones and such neuronal areas of the brain as the brain cortex, hypothalamus and basal ganglia (Sellinger & Hiatt, 1968;Sellinger & Nordrum, 1969;Idoyaga-Vargas et al, 1972;Roberts & Gorenstein, 1987). Our results also correspond well with those of other authors who observed a higher activity of lysosomal enzymes in a mixed neuronalglial culture than in astrocytes (Mandel et al, 1978), and reported a higher activity of those enzymes in a neuronal fraction than in a fraction containing oligodendrocytes or astrocytes (Freysz et al, 1979).…”

3Development‐Dependent Regulation of N‐Acetyl‐β‐d‐Hexosaminidase of Cerebellum and Cerebrum of Normal and Staggerer Mutant Mice

“…The activity increased almost threefold in the 1st postnatal month and remained at this level. The cerebrum-specific pattern was comparable to the pattern obtained for cerebrum and whole brain of the rat (Idoyaga-Vargas et al, 1972;Traurig et al, 1973;Zanetta et al, 1980).…”

“…(c) It appears unlikely that the change of cell populations in sg/sg as compared to normal cerebella accounts for the obvious enzymatic deviation at postnatal day 27, since weaver mutant mice of the same age, which lose granule cells to the same extent as do sg/sg, express entirely normal enzyme activities in this tissue (Figs, I and 2). Furthermore, Idoyaga-Vargas et al (1972) have reported almost identical N-acetyl-p-glucosaminidase activities for neuronal cell bodies and glial cells, indicating that the loss of cell types should not change the relative level of enzyme activity. Nevertheless, detailed localization studies of this enzyme activity in normal and mutant cerebella are needed to determine cellspecific enzyme activities.…”

“…Changes in glycosidase activity during development of CNS tissues have received much attention (Roukema et al, 1970;Ohman and Svennerholm, 1971;Idoyaga-Vargas et al, 1972;Traurig et al, 1973;Clarke, 1974;Zanetta et al, 1980). We have shown that a certain N-acetylneuraminidase is regulated in wild-type cerebellum and cerebrum.…”

Comparison of Postnatal Development of Several Acid Glycosidases in the Rat Forebrain and Cerebellum

“…At 3 days of age litter size was adjusted regardless of sex to give 8 -9 pups per dam. The animals were killed by decapitation on days 3,6,8,15,20 and 34. 2-month-old male rats were obtained from the same source, and sacrificed by decapitation at 90 days of age.…”