Zinc Deficiency: Effect on Brain of the Suckling Rat

1975

Pediatr Res

ExtractThe effect of zinc deficiency during the latter third of gestation on avoidance conditioning of young adult male rats was compared with the effect of intrauterine starvation and normal pregnancy. Animals which had experienced zinc deficiency avoided shock less well than the offspring of pair-fed control dams. The offspring of pair-fed dams avoided shock less well than animals which were the product of normal pregnancy. Response latencies were inferior in the zincdeficient group, whereas intertrial responses were less on both the previous zinc-deficient and intrauterine starved animals. SpeculationZinc is essential for development of the brain. Fetuses of women who consume inadequate amounts of zinc during pregnancy may be at risk as far as intrauterine brain development and body growth are concerned. Damage caused to such fetuses may be persistent and be mainfest as mental retardation.Zinc is essential for nucleic acid synthesis in the rat (1 8, 19, 23, 25) and protein (8,25) and, therefore, presumably in man. Perhaps becuase of its role in these aspects of metabolism, zinc deficiency has adverse effects on the brain of the fetal (9) and suckling (18) rat. The injury to the brain of the suckling rat is apparently poorly reversible, as behavioral tests of 60-t o 80-day-old rats which have been suckled by zinc-deficient dams until weaning have revealed impaired acquisition of the Tolman Honzig maze (12).The evidence that zinc is essential for muturation of the brain and that zinc deprivation during the critical period of brain growth results in persistent evidence of injury prompted us t o assess the effect of intrauterine zinc deficiency during the third trimester of gestation on subsequent avoidance conditioning of 60-day-old rats. Previous evidence that intrauterine malnutrition can cause persistent behavioral abnormalities in adult rats has been limited (21). MATERIALS AND METHODSTimed pregnant Sprague-Dawley rats were divided into three groups and individually housed in plastic cages with perforated bottoms in a light-and temperature-controlled environment. The dams were purchased timed pregnant from BioLabs (26) and the day of mating was counted as day 0. From the 15th through the 20th day of gestation they were fed a sprayed egg white, biotin-enriched diet containing < 1>0 ppm zinc (13).During this interval two groups served as controls. .One control group (five dams) was pair-fed with the zincdeficient group, while the second control group (five dams) was fed the diet ad libitum. Both control groups were given drinking water containing 50 ppm zinc via an automatic watering device. The zincdeficient group (five dams) were given trace mineral-free water via a central watering device. Before and after the "zinc-deficient interval," all dams were fed a standard laboratory rat chow ad libitum. Food consumption and weight gain of the dams were recorded during pregnancy and lactation. After delivery the number of pups per litter was made approximately equivalent. All litters thus contained 8-10 pups and ...

Section: Discussionmentioning

confidence: 88%

“…Zinc is essential for nucleic acid, protein, cerebroside, and lipid synthesis in the brain (4,5,18). Postnatal zinc deficiency severely retards biochemical development of the brain (4,5).…”

Section: Discussionmentioning

confidence: 99%

Section: Speculationmentioning

confidence: 99%

See 1 more Smart Citation

Some Effects of Prenatal Zinc Deficiency on Behavior of the Adult Rat

Halas

1975

Pediatr Res

“…Incorporation of thymidine into DNA was suppressed in 10-day-old sucklings (334). Histologic examination of the cerebellum on the 21st postnatal day found retarded maturation (335) and impaired division and migration of external granular cell neurons (336,337).…”

Section: Importance Of Zinc To Brain Devel-opment and Function: Animamentioning

confidence: 97%

Zinc: health effects and research priorities for the 1990s.

Walsh

Environ Health Perspect

Prasad

et al. 1994

267

This review critically summarizes the literature on the spectrum of health effects of zinc status, ranging from symptoms of zinc deficiency to excess exposure. Studies on zinc intake are reviewed in relation to optimum requirements as a function of age and sex. Current knowledge on the biochemical properties of zinc which are critical to the essential role of this metal in biological systems is summarized. Dietary and physiological factors influencing the bioavailability and utilization of zinc are considered with special attention to interactions with iron and copper status. The effects of zinc deficiency and toxicity are reviewed with respect to specific organs, immunological and reproductive function, and genotoxicity and carcinogenicity. Finally, key questions are identified where research is needed, such as the risks to human health of altered environmental distribution of zinc, assessment of zinc status in humans, effects of zinc status in relation to other essential metals on immune function, reproduction, neurological function, and the cardiovascular system, and mechanistic studies to further elucidate the biological effects of zinc at the molecular level. - There is considerable evidence that zinc deficiency in humans is a serious worldwide problem and outweighs the potential problem of accidental, self-imposed, or environmental exposure to zinc excess. Acute deficiency (1) and chronic deficiency (2) are well-known entities in human populations and are probably much more common than generally recognized. The importance of zinc for human health was first documented in 1963 (3) Telephone (617) (617) 638-4329. E-mail: ctwalsh~bu.edu renal disease, and other chronically debilitating diseases are now known to be predisposing factors for zinc deficiency in humans (4).Zinc deficiency is reflected in clinical syndromes which affect men and women of all ages and all socioeconomic and cultural classes in the United States. It is neither prevalent in any specific area of the United States nor associated with any specific or definitive biochemical marker, which can make its identification difficult and confusing. Its presence is manifested by a wide spectrum of symptoms, from acute, life threatening problems to mild subclinical or marginal disorders which may only vaguely disturb well being. The acute problems are often seen in profoundly ill patients treated in hospitals, whereas subclinical problems may be so vague that patients seek assistance outside traditional medical practice.Based upon clinical data and using traditional, epidemiologic techniques, Henkin and Aamodt (5) have reclassified zinc deficiency into three syndromes; these are a) acute, b) chronic, and c) subacute zinc deficiency. Acute zinc deficiency is relatively uncommon and follows parenteral hyperalimentation or oral L-histidine administration. Chronic zinc deficiency is more common, usually resulting from chronic dietary lack of zinc. Subacute or latent zinc deficiency is the most common of these syndromes. It is estimated that there are 4...

“…The 12-day-old zincdeficient pups also displayed a A deficiency of dietary zinc during the suckling period of decreased incorporation of thymidine into D~~ and of the rat results in a depression in normal growth, which is, in inorganic sulfate into the acid-insoluble fraction of brain (19). part, due to the inanition experienced by the dam.…”

Section: Extractmentioning

confidence: 99%

Some Effects of Postnatal Zinc Deficiency on Developing Rat Brain

Al-Ubaidi

1975

Pediatric Research

Extractpups suckled by zinc-adequate, pair-fed, or ad libitum-fed dams. The 12-day-old zincdeficient pups also displayed a A deficiency of dietary zinc during the suckling period of decreased incorporation of thymidine into D~~ and of the rat results in a depression in normal growth, which is, in inorganic sulfate into the acid-insoluble fraction of brain (19). part, due to the inanition experienced by the dam. The pups The studies reported in this paper are an extension of the from such zinc-deficient dams have smaller forebrains at all of above studies on effects of a deficiency of dietary zinc on the time intervals investigated in comparison with pups from brain composition and development during the suckling both zinc-adequate controls. The cell number of the forebrain period. of the zinc-deficient pup was also reduced in comparison with the zinc-adequate pups. RNA concentration did not appear to be affected, although the total RNA content was reduced METHODSbecause the smaller brain size. The protein per Pregnant Sprague-Dawley rats were fed an adequate ration cell was reduced at 6 and 15 days in the zinc-deficient ad libitum until delivery. soon as possible after parturition, forebrain and polysomal profiles displayed abnormal distribu-the dams were moved to clean Plexiglas cages. The number of tion of material between monosomes and polysomes in the in each litter was made equivalent at 8 and only litters zinc-deficient brain. Zinc deficiency during the suckling period that were maintained at or 8 pups during the test period thus appears to disadvantage the animal in terms of body, were used for analysis.animals were then fed a brain growth, accretion of cells into the forebrain, and normal biotin-enriched, 20% sprayed egg white diet (13) which was protein metabolism.modified to incorporate inositol at 1 g/kg and to omit the antibiotic. The zinc content was less than 1 mg/kg by analysis. Speculation One group of dams was given the diet ad libitum and distilled, zinc is essential for development of the brain. infants who deionized water to drink. Two zinc-adequate controls were experience zinc deficiency during the critical period for brain utilized. The first was pair-fed on an individual basis with the growth will suffer brain damage which may be poorly dams in the zinc-deficient group. The second control was fed reversible.the diet ad libitum. Both zinc-adequate controls received zinc at 100 mg/liter in their drinking water. At intervals, the entire litter of a dam was killed by Zinc has been known to be an essential trace element for decapitation. The brains were rapidly removed, separated by more than a century (17), although its essentiality for a blunt dissection into cerebellum and forebrain (the brain mammalian species was not established until 1934 (28), when anterior to the cerebellum excluding the brain stem and the deficiency syndrome was produced in rats. The manifesta-olfactory bulbs), and placed in ice-cold, buffered sucrose. tions of zinc deficiency have been reviewed by Underwood After wei...