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Postnatal exposure (from the second day after birth to 30 days) of rat pups to low levels of lead acetate (50 mg/kg body weight/day), administered by gastric intubation, yielded a maximum blood level of 76.1 micrograms/100 ml, at day 15 of age. Cerebellar and hippocampal lead contents were 8.67 micrograms/100 mg and 11.7 micrograms/100 mg, respectively, at day 30 of age. This lead exposure has been shown to elicit little change in some biochemical parameters in cerebellum and hippocampus. At the three ages investigated (5, 15, and 30 days after birth) there were no alterations of body weight; brain, cerebellum, and hippocampus wet weight; and DNA, RNA, protein and phospholipid content, either in total tissue or in mitochondria. A similar invariance following lead exposure was observed in mitochondrial succinate dehydrogenase and cytochrome oxidase activities. After intraperitoneal administration, the incorporation of [methyl-14C]thymidine into DNA and [5,6-3H]uridine into RNA of cerebellum and hippocampus showed a significant decrease only at day 5, reaching the control value at 15 and 30 days of age. After intraperitoneal injection, [2-3H]glycerol incorporation into total lipids and phospholipids of cerebellum and hippocampus also showed no significant changes in Pb-treated pups compared to controls at all three postnatal ages. We concluded that subclinical lead administration exerts its effect by slowing cell proliferation in the very early growth phase of the brain. It is likely that a metabolic compensative response to subtoxic effect of lead acetate may be brought about in cerebellum and hippocampus during critical phases of nervous system development between days 15 and 30.

Hypoxic treatment causes changes of some enzymatic activities involved in the glycerolipid metabolism in subcellular fractions of guinea pig cerebral hemispheres. The activity of lysophosphatidylcholine acyltransferase, choline phosphotransferase, glycerol-3-phosphate acyltransferase(s), as well as the activity of triacylglycerol lipase significantly decreased in the microsomes of cerebral hemispheres of animals intermittently exposed to hypoxic treatment for eighty hours. At the same time, a marked activation of microsomal and mitochondrial phospholipase A2 occurred. The changes of the above-mentioned enzymatic activities after the hypoxic treatment correlated well with the increase in the level of brain and blood free fatty acids. The changes also correlated with the decrease of labeled lipid precursors incorporated into lipids of the cerebral hemispheres, observed during oxygen insufficiency.

Acute administration of CDP-choline (i.p. 100 mg/Kg b.w.), 10 min before the intraventricular injection of labeled precursors, [2-3H] glycerol and [1-14C]-palmitate, was able to correct the impairment caused by hypoxic treatment of lipid metabolism in some brain regions, ie, cerebral hemispheres, cerebellum, and brainstem. After CDP-choline treatment, an increase of the specific radioactivity of total lipids and of phospholipids was observed in mitochondria purified from the three above-mentioned brain regions of the hypoxic animals, while no effect on the other subcellular fractions was found. CDP-Choline had a stimulating effect particularly on the incorporation of both precursors into mitochondrial PC, PE, and polyglycerophosphatides isolated form the three brain regions examined. The results obtained show that the action of CDP-choline in restoring lipid metabolism was more pronounced in brain mitochondria, which, among subcellular fractions, were the most affected by the hypoxic treatment.

The effect of age upon the axoplasmic transport of glycerophospholipids has been studied using as a model the regenerating sciatic nerve of young (2-month-old), young adult (6-month-old), middle-aged (16-month-old), and aged (20-month-old) male rats. The right sciatic nerve was crushed 0.5 mm down the incisura ischiadica. Four and nine days after the lesion, a mixture of [2-3H] glycerol and [methyl-14C] choline was bilaterally injected into the spinal cord, at a level of the L4-L5 vertebrae. The animals were killed 18 hr after the isotope injection. Proximal and distal portions of crushed nerve and of contralateral sham-operated ones were dissected and consecutive 5-mm segments were subjected to lipid extraction and analysis. The findings of the present study are summarized as follows: (1) The accumulation of labeled lipid material axonally transported four days after nerve injury was mainly located at the crush site in young, young adult, middle-aged, and aged rats. The accumulation of both 3H-glycerolipids and 14C-choline phospholipids in postcrush segments was markedly higher for young and young adult than for aged rats, four and nine days after crush; (2) the average rate of axonal regeneration, determined between days 4 and 9 following crush injury was 3.6 and 4.2 mm/day for 2-month-old and 6-month-old rats, respectively; it decreased to the value of 2.5 mm/day for 16–20-month-old rats.

At different time intervals (4 hr up to 24 days) after intravitreal injection of myo-(2-3H)-inositol, the specific activity (sp act) of phosphatidylinositol (PtdIns) and water-soluble compounds extracted from the retina, optic nerve (ON), optic tract (OT), lateral geniculate body (LGB), and superior colliculus (SC) was measured. Furthermore, 2 days after biocular injection of the labeled precursor, the specific activity of PtdIns and other major phospholipids in the various subcellular fractions (myelin, axolemma, synaptosomes, mitochondria, and microsomes) purified from ON + OT, from LGB, and from SC was evaluated. In the ON and OT, the phospholipids were labeled 8 hr after the precursor injection; in the LGB and SC after 8–12 hr. In all the optic components examined, the lipid specific activity reached a maximum at day 6 and decreased slowly until day 24 after injection. In the ON + OT, the specific activity of PtdIns, isolated from various subcellular fractions, decreased as follows: myelin > axolemma; in the LGB and SC as follows: microsomes > synaptosomes > myelin > mitochondria. The radioactivity present in the retina and in the optic pathway was exclusively localized in the PtdIns during the whole time interval studied. Ten days after the precursor injection, a high portion of the radioactivity transported was detected in the water-soluble pool, separated from the ON and OT, whereas no significant counts in the corresponding LGB and SC pool were found. The kinetics of PtdIns labeling, observed in the different optic components, indicated a rapid axonal transport of the phospholipid; besides, the presence of labeled PtdIns in the purified myelin suggested a transaxonal migration of the phospholipid and its free precursor.

The pool size of CDP-choline in the brain, heart, and lung of normal and hypoxic animals was measured by radioactive isotopic dilution. The effect of exogenous CDP-choline administration on the pool size in these experimental groups was also examined. The hypoxic treatment caused a significant decrease of endogenous CDP-choline in the brain and lung only; no significant effect was observed in the examined organs after CDP-choline treatment.

The lipid metabolism in guinea pig brain after intermittent hypoxia, prolonged for 80 hrs, was markedly impaired. The in vivo incorporation of [2-3H] glycerol adn [1-14C] palmitate into lipids of microsomes, mitochondria, myelin, and synaptosomes, purified form cerebral hemispheres, was significantly lower in the hypoxic animals than in the controls. The same effect was observed on the incorporation of labeled precursors into lipids of mitochondria purified from cerebellum and brainstem. In particular, the labeling of th major phospholipids present - ie, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) - in the mitochondria of the three brain regions examined decreased after hypoxic treatment.

An axolemma-enriched fraction was isolated and characterized from homogenates of brain stem, pooled optic nerve and tract, and sciatic and hypoglossal nerves of adult rabbits. In these fractions, the phospholipase A1 and A2, as well as the activity of acyl-CoA:1-acyl-sn-glycero-3-phosphorylcholine and acyl-CoA:2-acyl-sn-glycero-3-phosphorylcholine acetyl transferase, using 1-acyl- and 2-acyl-GPC as acyl acceptors, were studied. The activity of the four enzymes was clearly detectable in the central nervous system (CNS) and peripheral nervous system (PNS) axolemmatic preparations, as well as in other subcellular fractions examined. The axolemma fractions, in which acetylcholinesterase displayed the highest activities, were particularly enriched in the acylation reaction enzymes. These latter showed specific activities about twofold higher compared with those of the homogenates and significant correlation with acetylcholinesterase. The noticeable presence of these enzyme activities in both CNS and PNS axolemma suggests that a deacylation-reacylation system for phospholipids may be operative in this membrane.