Influence of Nutritional Deprivations in Early Life on Learning Behavior of Rats as Measured by Performance in a Water Maze

Barnes, Richard H.; Cunnold, Susan Robertson; Zimmermann, Robert R.; Simmons, Howard James; MacLeod, Robert B.; Krook, L

doi:10.1093/jn/89.4.399

Cited by 154 publications

(35 citation statements)

References 10 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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“…There have been many reports which found that as a consequence of infantile undernutrition, persistent changes take place in central catecholaminergic systems,""" protein metabolism, 18 cellularity,*-•• u body weight gain,*" 11 and behavior, 19 " 0 even after a prolonged period of nutritional recovery. A persistent growth retardation in SHRSP with a history of post- natal undcrnutrition suggests an occurrence of similar changes in SHRSP to those described above.…”

Section: Discussionmentioning

confidence: 99%

Postnatal undernutrition accelerates incidence of stroke in stroke-prone spontaneously hypertensive rats.

Matsuo¹,

Nagaoka²

1981

Stroke

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509SUMMARY The effect of infantile nutritional levels on the derelopment of hypertension and incidence of stroke was inrestigated in stroke-prooe spontaneously hypertensive rats (SHRSP). Caloric intake was raried during the suckling period by manipulating litter size immediately after birth; however, all animals had free access to food after weaning. Animals reared in large litters of 15 (LL group) weighed significantly less than those in small litters of 5 (SL group) at every age. In the LL group, systolic Mood pressure (mean ± SD) Increased age-dependently to reach 237 ± 16 mm Hg at 14 weeks of age, and 14 of 15 rats developed stroke from 14 to 19 weeks of age. On the other hand, in the SL group, the blood pressure at 14 weeks of age was 213 ± 6 mm Hg, which was significantly lower than that in LL group, and stroke occurred only in 3 of 10 rats kept up to 22 weeks.When the drinking water was replaced with a 1% salt solution, the onset of stroke markedly accelerated in both groups; more than 90% of rats developed stroke within 18 days after the salt-loading. However, the time required for the onset of stroke signs was significantly shorter in the LL group (10.5 ± 1 3 days) than in the SL group (15.4 ± 1.7 days). Furthermore, the blood pressure Increment for the first week after the salt-loading was significantly greater in the LL group (293 ± 9.5 mm Hg) than in the SL group (14.2 ± 3.0 mm Hg).These findings indicate that infantile undernotrition may accelerate the development of hypertension and incidence of stroke in SHRSP. Stroke, Vol 12, No 4, 1981STROKE-PRONE spontaneously hypertensive rats (SHRSP), established by Okamoto et al. 1 from spontaneously hypertensive rats (SHR), are used as a model of human hypertension and stroke. SHRSP are more hypertensive and develop cerebrovascular lesions with a much higher frequency than the original strain. The development of the disorders can be modulated by diets; either a high protein diet or high fat diet containing a moderate amount of protein has suppressive effects, but a low protein diet accelerates the disorders.1 '' It is well known that infantile nutritional levels have profound and permanent effects on animal development. In the present study, we investigated whether infantile nutritional levels might affect the development of hypertension and occurrence of stroke in SHRSP by manipulating litter size immediately after birth in a manner similar to that described by Kennedy 4 and Widdowson and McCane.' Methods Pregnant SHRSP with known conception times and their offsprings were used. Within 24 hours of the birth, only males from the litters consisting of 8-10 pups were distributed to form a litter size of 5 or 15, because of a much higher incidence and developmental rate of stroke in the males than in the females of

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“…Sex differences in response to limbic system lesions have also been documented (Goldman, Cranford, Stokes, Galkin, & Rosvold, 1974), and with hippocampal damage it has even been reported that anomalous axonal sprouting is less intense in male than in female rats (Loy & Milner, 1980). Gender differences have also been found in studies of undernutrition (Barnes, Cunnold, Zimmerman, Simmons, MacLeod, & Krook, 1966;Barnes, Moore, Reid, & Pond, 1977;Crnic, Bell, Mangold, Gruenthal, Eiler, & Finger, 1981;Kennedy, 1957), with the bulk of the evidence suggesting that males may be somewhat more susceptible to the effects of early nutritional insult than females. Nevertheless, since only females were run on the DRL tasks and only males on the four tasks used here, further testing is needed to clarify and determine the relative roles of gender and task in accounting for the differential results obtained in this and the previous study.…”

Section: Discussionmentioning

confidence: 94%

Early undernutrition and later hippocampal damage: Effects on spontaneous behaviors and reversal learning

Laughlin¹,

Finger²,

Bell³

1983

Psychobiology

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Rats from dams that were well fed or underfed (50% food reduction) during lactation received either large lesions of the dorsal hippocampus or sham operations at 60 days of age. The animals then were tested for open-field behavior, spontaneous alternation, spontaneous exploration, and spat~al discrimination reversal learning. Main effects of nutrition were found in the open field and on the spatial learning and reversal tasks, as well as in body weight, eye opening, and time of appearance of body hair. Significant lesion effects were found in the open field and on spontaneous alternation and reversal learning. In contrast to two earlier studies, early diet had little effect on the response to later brain damage. These data show that the finding that early diet can affect the behavioral response to focal brain damage later in life may not generalize across all experimental conditions.

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Influence of Nutritional Deprivations in Early Life on Learning Behavior of Rats as Measured by Performance in a Water Maze

Cited by 154 publications

References 10 publications

Detrimental Effects of the Ketogenic Diet on Cognitive Function in Rats

Detrimental Effects of the Ketogenic Diet on Cognitive Function in Rats

Postnatal undernutrition accelerates incidence of stroke in stroke-prone spontaneously hypertensive rats.

Early undernutrition and later hippocampal damage: Effects on spontaneous behaviors and reversal learning

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