Early-life undernutrition impairs the development of the learning and short-term memory processes mediating performance in a conditional-spatial discrimination task

Castro, Carl A.; Tracy, Michael C.; Rudy, Jerry W.

doi:10.1016/s0166-4328(89)80058-0

Cited by 53 publications

(37 citation statements)

References 33 publications

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“…However, despite these changes in brain development, cognitive effects of malnutrition have been variable (51) with impairment of learning and spatial memory after early malnutrition described by some authors (52)(53)(54)(55)(56)(57)(58), whereas other have not found any differences (59 -62). Timing of the cognitive task seems to be an important factor: spatial learning ability of undernourished young rats was substantially impaired compared with performance after nutritional rehabilitation (59).…”

Section: Discussionmentioning

confidence: 99%

Detrimental Effects of the Ketogenic Diet on Cognitive Function in Rats

et al. 2004

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The ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that is widely used to treat epilepsy in children. Although the KD has been shown to be efficacious in the treatment of childhood epilepsy, the long-term effects of the KD on brain development are not clear. The objective of this study was to examine the long-term effects of the KD on visual-spatial memory, activity level, and emotionality in immature rats after status epilepticus (SE). Weanling rats were subjected to lithium/ pilocarpine-induced SE or saline injections and were then randomized to either the KD or regular rat diet, both fed ad libitum. One month later, rats were evaluated for visual-spatial memory in the water maze, activity level in the open field test, and emotionality with the handling test. Spontaneous recurrent seizures were measured using videotaping, and seizure susceptibility was tested with flurothyl inhalation. Brains were weighed and examined for mossy fiber sprouting and cell loss. Although rats treated with the KD were active and seemed healthy, their weight gain was substantially lower than that in rats that received regular rat diet. The KD reduced the number of spontaneous seizures but had no discernible effect on flurothyl seizure susceptibility. KDfed rats, with or without SE, had significantly impaired visualspatial learning and memory compared with rats that were fed regular diet. The KD had minimal effects on activity level and emotionality. Rats that were treated with the KD had significantly impaired brain growth. No differences in pathology scores between the KD and regular diet groups were seen after SE. Despite reducing the number of spontaneous seizures after SE, the KD resulted in severe impairment in visual-spatial memory and decreased brain growth, with no effect on mossy fiber sprouting. This study raises concerns about the long-term effects of the KD on brain development. The ketogenic diet (KD) is a high-fat, low-carbohydrate, and low-protein diet that is now widely used to treat epilepsy (1-4). Although the diet has not undergone the rigorous evaluation process required for marketing of antiepileptic drugs, there is now a considerable body of evidence indicating that the KD is efficacious in the treatment of epilepsy (1,2,5,6).Despite the use of the KD over several decades, the long-term effects of the KD on cognition are not yet known. Anecdotal reports suggest improvements in alertness, cognitive function, and behavior (2), although impairments in patients have also been reported (7). In a prospective study on the effects of the KD, Pulsifer et al. (8) found that developmental quotients in children on the diet improved after 1 y. One of the difficulties in evaluating cognitive effects of the KD in children is that the diet is rarely continued in children who do not respond with a reduction in seizure frequency (5, 9). The improvement in cognitive function therefore may represent the effects of reduced seizures, a positive cognitive effect of the diet, or a combination of these facto...

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Section: Discussionmentioning

confidence: 99%

Detrimental Effects of the Ketogenic Diet on Cognitive Function in Rats

et al. 2004

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“…Perhaps more intriguing, however, are the results of studies using non-spatial, hippocampal-sensitive tasks that suggest that the hippocampal formation contributes to earlier developing memory functions as measured, for example, by patterned alternation (Diaz-Granados et al 1992), or olfactory reversal learning (Saperstein et al 1989) emerge before complete hippocampal maturation. Conversely, successful performance on tasks such as spatial delayed alternation (Castro et al 1987) and transverse patterning (J.W. Rudy and M.C.…”

Section: Maturation Of Medial Temporal Lobe Memory Functionsmentioning

confidence: 99%

Revisiting the Maturation of Medial Temporal Lobe Memory Functions in Primates

Alvarado¹,

Bachevalier²

2000

Learn. Mem.

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In a review of the literature on the development of the medial temporal lobe region in humans, monkeys, and rodents, Bachevalier and Beauregard indicated that in primates, memory functions subserved by this neural system emerge early in life and increment gradually with further postnatal maturation. Furthermore, they stated that the late-developing memory functions of normal neonates was more likely owing to the slow maturation of the association areas of the cortex than to the slow maturation of the hippocampal formation. This conclusion was based on the limited knowledge concerning the development of hippocampal-dependent memory functions and the maturational events in the medial temporal lobe of monkeys. Over the last decade, however, more information has accumulated about the structural, functional, and behavioral changes occurring throughout ontogeny in monkeys that suggest a refinement of this view. Whereas there is still much to be discovered, we thought it timely to put into perspective the latest findings in hope of shedding light on memory development in general, and particularly, on the role of medial temporal lobe structures in infant and adult memory. [Note: Hippocampal formation refers to the hippocampus proper (Ammon's fields), dentate gyrus, and subicular complex. Hippocampal region refers to the hippocampal formation and the adjacent entorhinal, perirhinal, and parahippocampal cortex.]It is generally accepted that memory is not a unitary process, but rather consists of multiple systems (for review, see Squire 1994), only one of which depends critically upon the hippocampal formation. The dissociation between these memory systems has received further support from developmental studies of memory in which it has been shown that memory processes that are sensitive to hippocampal dysfunction in adults are late developing in infants. Such findings have been particularly well documented in rodents. Because neurogenesis in the rodent dentate gyrus is almost entirely postnatal, the onset of particular behavioral events can be readily compared to maturational changes in the hippocampal formation (Altman et al. 1973;Douglas 1975). In particular, these behavioral functions emerge between ages 20 and 25 d, just at the end of neurogenesis and synaptogenesis in the dentate gyrus (Altman and Das 1965;Altman and Bayer 1975;Bayer 1980). For example, the ability to navigate to a hidden platform in a water maze or perform a delayed alternation task (Freeman and Stanton 1991) first appears at this age and is impaired in adults with damage to the hippocampal formation (Morris et al. 1982). This tight link between maturational events within the rodent hippocampal formation and associated structures and emergence of memory abilities has encouraged the extension of these comparisons to other species, including human and non-human primates.One striking difference between rodent and primate species is that the neurogenesis of the hippocampus proper and dentate gyrus in monkeys and humans is almost entirely prenatal Ecken...

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“…For example, young rats do not show spontaneous alternation on a Y-maze, although they explore at a rate similar to that of mature animals (Douglas, 1975). Spontaneous alternation, like other behaviors that seem to require hippocampal f unction in adult rats, emerges after ϳ3 weeks of age (Douglas, 1975;Moye and Rudy, 1985;Castro et al, 1987;Rudy et al, 1987;Green and Stanton, 1989;Randall, 1992, 1995;Rudy, 1993;Rudy and Morledge, 1994). Much of hippocampal synaptogenesis occurs postnatally (Crain et al, 1973;Stirling and Bliss, 1978;Bayer, 1980;Amaral and Dent, 1981;Baudry et al, 1981;Amaral and Kurz, 1985), and hippocampal synapses exhibit plasticity before the emergence of mature behavioral function (Harris and Teyler, 1984;Muller et al, 1989;Bekenstein and Lothman, 1991).…”

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confidence: 99%

Insensitivity of the Hippocampus to Environmental Stimulation during Postnatal Development

1997

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Development of cortical sensory systems is influenced by environmental experience during "sensitive periods," before onset of behavioral function. During these periods, synaptic plasticity is observed, and neuronal function shows increased responsiveness to environmental stimulation. Because the hippocampus is late to develop, and because it demonstrates synaptic plasticity before the onset of behavioral function, this experiment was designed to determine whether, like the sensory cortices, the hippocampus undergoes a period of enhanced responsiveness to the environment. Rats at three ages [postnatal day 16 (P16), P23, and P30] were tested on a hippocampally dependent task, spontaneous alternation, and exposed to a novel environment. They were then killed and processed for immunocytochemistry to Fos or for in vitro electrophysiology in hippocampal area CA1. Age-matched control subjects were killed immediately after removal from the home cage. Spontaneous alternation was only observed in the oldest (P30) animals. In these same animals, the environmental manipulation resulted in an increase in Fos-like immunoreactivity (FL-IR), relative to controls, and a decrease in the ability to induce long-term potentiation (LTP). In P16 and P23 animals, the environmental manipulation resulted in no differences in hippocampal FL-IR or LTP. These results suggest that, rather than showing increased responsiveness to the environment at these ages, the hippocampus is environmentally insensitive and that it is isolated from the effects of environmental stimuli. The hippocampus, a neural region important for higher cognitive function, may develop via a mechanism different from those observed in the primary sensory cortices.

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Early-life undernutrition impairs the development of the learning and short-term memory processes mediating performance in a conditional-spatial discrimination task

Cited by 53 publications

References 33 publications

Detrimental Effects of the Ketogenic Diet on Cognitive Function in Rats

Detrimental Effects of the Ketogenic Diet on Cognitive Function in Rats

Revisiting the Maturation of Medial Temporal Lobe Memory Functions in Primates

Insensitivity of the Hippocampus to Environmental Stimulation during Postnatal Development

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