- Email: [email protected]
Effect of early undernutrition on reactivity of the rat parietal association area
EXPERIMENTAL
NEUROLOGY
82, 241-244 (1983)
RESEARCH
NOTE
Effect of Early Undernutrition on Reactivity the Rat Parietal Association Area
of
HERNAN PEREZ, SAMUEL Ruiz, ALEJANDRO HERNANDEZ, AND RUBEN SOTO MOYANO’ Laboratorio de Neurojisiologia y Biojisica. Institute de Nutrici6n. Universidad de Chile, Santiago, 11, Chile Received February 4. 1983: revision received May 23, 1983 Cortical reactivity of parietal association area was studied in normal and undernourished rats. (i) The normal group was from mothers which were fed a 2 1.5% protein diet during lactation. (ii) The undernourished group was from mothers which were fed a 6.5% protein diet during the same period. At 21 days of age (weaning age) all animals received the same diet as that fed to the normal group. At 45 days of age, cortical chronaxie and fatigability of direct cortical responses were evaluated. The results showed that postnatal malnutrition induced alterations on cortical reactivity of that area.
It is well established that higher brain functions are closely related to association areas of the cerebral cortex (9). The parietal association area (PAA), for example, is currently viewed as a region for integrating visual and somatosensory afferent inputs with behavioral information. This role of the PAA has been largely confirmed by electrophysiological studies in freely moving animals (8). On the other hand, there is considerable experimental evidence indicating that early malnutrition causes structural and electrophysiologic changes in the cerebral cortex, behavioral disturbances, and lower scores in learning tasks (6). In man, early nutritional deficiencies in addition to disturbing the Abbreviations: DCR-direct cortical response, PAA-parietal association area. ’ We are grateful to Dr. Samuel Middleton for his help in the preparation of the manuscript. This work was supported by grant B-1509-8322 from the University of Chile. 241 0014-4886/83 $3.00 Copyright IPI 1981 by Academic Press. Inc All rights of reproduction in an) form rewved.
PGREZ
ET AL.
normal chemical composition of the nervous system and thereby its structure or function, also affects intellectual development and perceptual-motor abilities (5). We investigated the effects of early postnatal malnutrition on the reactivity of the PAA by determining thresholds of response to direct cortical stimulation. Fatigability to repetitive stimulation was also evaluated. The experiments were carried out in 18 Wistar rats (male or female) from two groups: (i) the normal group (N = 9, from three separate litters) whose mothers were fed a 2 1.5% protein diet during the lactation period and (ii) the undernourished group (N = 9, from three separate litters) from mothers fed, during the same period, a 6.5% protein diet which caused reduced milk production. Litter sizes were adjusted so that every mother nursed eight pups. After weaning at 2 1 days of age, all animals received the same diet fed to the normal group. The body weights of the pups were monitored periodically. At 45 days of age, the animals were weighed and anesthetized with 100 mg/kg cY-chloralose i.p. and then placed in a Horsley-Clarke stereotaxic apparatus; 1.5 mg/kg D-tubocurarine i.m. was injected and adequate ventilation was supplied by means of a respiration pump. Direct cortical responses (DCRs) were conventionally recorded from the PAA (de Groot’s coordinates A 1.0 to 4.0, L 1.O to 4.0, in millimeters). We measured (a) excitability, by evaluating the cortical chronaxie according to the procedure reported elsewhere (4, 10); (b) fatigability, by increasing the stimulus frequency until the I -mV amplitude DCRs were diminished by 50%. The reduction in body weight (Table 1) of the undernourished group compared with the normal group showed that there was a severe nutritional impairment during lactation in spite of the 24 days rehabilitation period. The brain weight was also found diminished (Table 1), and might reflect irreversible damage induced by undernutrition during the period of rapid brain growth (2). The malnourished group showed a significant increase of cortical chronaxie values as well as increased fatigability of DCRs (Table 1). In previous work it has been shown that cortical chronaxie is a physiologic index of cortical excitability (4) a greater chronaxie indicating a lower excitability. In our experiments, therefore, the significant increase of the PAA chronaxie in malnourished rats could be interpreted as due to a decreased excitability of PAA neural elements, caused by morphologic and metabolic impairment of neural structures involved in the DCR generation. According to the literature (7) these structures could be (a) the excitable membrane of the presynaptic endings, and/or, (b) the axodendritic synapses mediating the response. This second alternative appears as more plausible because according to published data nutritional deprivation induces lower synaptic density (3) and disorders of neurotransmitter metabolism (1 I ). Axodendritic involvement would be further
CORTICAL
REACTIVITY
243
IN UNDERNUTRITION
TABLE 1 Reactivity of Rat Parietal Association Area” Normal group N=9
Body weight (g) Brain weight (g) Chronaxie (ps) Fatigability (Hz)
182.2 f 5.3 1.68 * 0.02 78.9 f 3.6
1.31 s 0.06
Undernourished group N=9 123.8 1.50 98.4 0.92
f + + ?z
4.3* 0.03* 4.1; 0.07*
’ Mean + SE. Determinations carried out at 45 days of age. * P < 0.005 according to Student’s I test.
supported by the great fatigability to repetitive cortical stimulation found in the undernourished rats. In fact, it seems to be well established that gray matter fatigability depends fundamentally on synaptic properties. With regard to the first alternative it has been proved that early postnatal malnutrition induces long-term deficits in brain myelination of fibers (1). However, preliminary experiments carried out in our laboratory showed that there were no significant differences in latency times in the DCRs between normal and malnourished rats. Further studies are required to elucidate this question, as no other structural or metabolic alterations of the membrane of presynaptic nerve endings have been reported so far in this experimental model of malnutrition. In summary, early postnatal malnutrition alters the responsiveness of the PAA suggesting damage at the level of the cortical neural elements participating in association processes. REFERENCES 1. DAVISON, A. N., AND J. DOBBING. 1966. Myelination as a vulnerable period in brain development. Br. Med. Bull. 22: 40-44. 2. DOBBING, J. 1968. Vulnerable periods in developing brain. Pages 287-3 16 in A. N. DAVISON AND J. DOBBING, Eds., Applied Neurochemistry. Oxford Press, Oxford. 3. GAMBETTI, P., L. A. GAMBETTI, N. RIZZUTO, B. SHAFER, AND L. PFAFF. 1974. Synapses and malnutrition: quantitative ultrastructural study of rat cerebral cortex. Exp. Neural. 43: 464-473.
HERNANDEZ, A., AND H. I%REZ. 1981. The strength-duration function in the evocation of direct cortical responses. Int. J. Neurosci. 12: 29-32. 5. MONCKEBERG, F. 1969. Malnutrition and mental behavior. Nutr. Rev. 27: 191-193. 6. MORGANE, P. J., M. MILLER, T. KEMPER, W. STERN, W. FORBES,R. HALL, J. BRONZINO, J. KKSANE, E. HA~RYLE~KX, AND 0. RESNICK. 1978. The effectsof protein mahrutrition on the developing central nervous system in the rat. Neurosci. Biobehav. Rev. 2: 1374.
230.
PEREZ ET AL.
244 7.
J. W., AND S. OCHS. 197 1. Occlusive behavior of the negative wave direct cortical response (DCR) and single cells in the cortex. J. Neurophysiol. 34: 374-388. 8. ROBINSON,D. L., AND M. GOLDBERG. 1978. Sensory and behavioral properties of neurons in posterior parietal cortex of awake trained monkey. Fed. Proc. 37: 2258-226 1. 9. SCHERRER,J., AND Y. BLJRNOD. 1978. Some electrophysiological data about neocortical association areas. Pages 393-405 in M. A. BRAZIER AND H. PETSCHE, Eds., Architecfonics of the Cerebral Cortex. Raven Press, New York. 10. SOTO MOYANO, R., S. Ruiz, H. PEREZ, R. CARRILLO, AND A. HERNANDEZ. 1981. Effect of prenatal malnutrition on cortical reactivity of the rat parietal association area. Int. J. Neurosci. 13: 99-102. 11. STERN, W. C., M. MILLER, W. B. FORBES,P. J. MORGANE, AND 0. RESNICK. 1975. Ontogeny of the levels of biogenic amines in various parts of the brain and peripheral tissues in normal and protein malnourished rats. Exp. Neural. 49: 3 14-326. PHILLIPS,
NEUROLOGY
82, 241-244 (1983)
RESEARCH
NOTE
Effect of Early Undernutrition on Reactivity the Rat Parietal Association Area
of
HERNAN PEREZ, SAMUEL Ruiz, ALEJANDRO HERNANDEZ, AND RUBEN SOTO MOYANO’ Laboratorio de Neurojisiologia y Biojisica. Institute de Nutrici6n. Universidad de Chile, Santiago, 11, Chile Received February 4. 1983: revision received May 23, 1983 Cortical reactivity of parietal association area was studied in normal and undernourished rats. (i) The normal group was from mothers which were fed a 2 1.5% protein diet during lactation. (ii) The undernourished group was from mothers which were fed a 6.5% protein diet during the same period. At 21 days of age (weaning age) all animals received the same diet as that fed to the normal group. At 45 days of age, cortical chronaxie and fatigability of direct cortical responses were evaluated. The results showed that postnatal malnutrition induced alterations on cortical reactivity of that area.
It is well established that higher brain functions are closely related to association areas of the cerebral cortex (9). The parietal association area (PAA), for example, is currently viewed as a region for integrating visual and somatosensory afferent inputs with behavioral information. This role of the PAA has been largely confirmed by electrophysiological studies in freely moving animals (8). On the other hand, there is considerable experimental evidence indicating that early malnutrition causes structural and electrophysiologic changes in the cerebral cortex, behavioral disturbances, and lower scores in learning tasks (6). In man, early nutritional deficiencies in addition to disturbing the Abbreviations: DCR-direct cortical response, PAA-parietal association area. ’ We are grateful to Dr. Samuel Middleton for his help in the preparation of the manuscript. This work was supported by grant B-1509-8322 from the University of Chile. 241 0014-4886/83 $3.00 Copyright IPI 1981 by Academic Press. Inc All rights of reproduction in an) form rewved.
PGREZ
ET AL.
normal chemical composition of the nervous system and thereby its structure or function, also affects intellectual development and perceptual-motor abilities (5). We investigated the effects of early postnatal malnutrition on the reactivity of the PAA by determining thresholds of response to direct cortical stimulation. Fatigability to repetitive stimulation was also evaluated. The experiments were carried out in 18 Wistar rats (male or female) from two groups: (i) the normal group (N = 9, from three separate litters) whose mothers were fed a 2 1.5% protein diet during the lactation period and (ii) the undernourished group (N = 9, from three separate litters) from mothers fed, during the same period, a 6.5% protein diet which caused reduced milk production. Litter sizes were adjusted so that every mother nursed eight pups. After weaning at 2 1 days of age, all animals received the same diet fed to the normal group. The body weights of the pups were monitored periodically. At 45 days of age, the animals were weighed and anesthetized with 100 mg/kg cY-chloralose i.p. and then placed in a Horsley-Clarke stereotaxic apparatus; 1.5 mg/kg D-tubocurarine i.m. was injected and adequate ventilation was supplied by means of a respiration pump. Direct cortical responses (DCRs) were conventionally recorded from the PAA (de Groot’s coordinates A 1.0 to 4.0, L 1.O to 4.0, in millimeters). We measured (a) excitability, by evaluating the cortical chronaxie according to the procedure reported elsewhere (4, 10); (b) fatigability, by increasing the stimulus frequency until the I -mV amplitude DCRs were diminished by 50%. The reduction in body weight (Table 1) of the undernourished group compared with the normal group showed that there was a severe nutritional impairment during lactation in spite of the 24 days rehabilitation period. The brain weight was also found diminished (Table 1), and might reflect irreversible damage induced by undernutrition during the period of rapid brain growth (2). The malnourished group showed a significant increase of cortical chronaxie values as well as increased fatigability of DCRs (Table 1). In previous work it has been shown that cortical chronaxie is a physiologic index of cortical excitability (4) a greater chronaxie indicating a lower excitability. In our experiments, therefore, the significant increase of the PAA chronaxie in malnourished rats could be interpreted as due to a decreased excitability of PAA neural elements, caused by morphologic and metabolic impairment of neural structures involved in the DCR generation. According to the literature (7) these structures could be (a) the excitable membrane of the presynaptic endings, and/or, (b) the axodendritic synapses mediating the response. This second alternative appears as more plausible because according to published data nutritional deprivation induces lower synaptic density (3) and disorders of neurotransmitter metabolism (1 I ). Axodendritic involvement would be further
CORTICAL
REACTIVITY
243
IN UNDERNUTRITION
TABLE 1 Reactivity of Rat Parietal Association Area” Normal group N=9
Body weight (g) Brain weight (g) Chronaxie (ps) Fatigability (Hz)
182.2 f 5.3 1.68 * 0.02 78.9 f 3.6
1.31 s 0.06
Undernourished group N=9 123.8 1.50 98.4 0.92
f + + ?z
4.3* 0.03* 4.1; 0.07*
’ Mean + SE. Determinations carried out at 45 days of age. * P < 0.005 according to Student’s I test.
supported by the great fatigability to repetitive cortical stimulation found in the undernourished rats. In fact, it seems to be well established that gray matter fatigability depends fundamentally on synaptic properties. With regard to the first alternative it has been proved that early postnatal malnutrition induces long-term deficits in brain myelination of fibers (1). However, preliminary experiments carried out in our laboratory showed that there were no significant differences in latency times in the DCRs between normal and malnourished rats. Further studies are required to elucidate this question, as no other structural or metabolic alterations of the membrane of presynaptic nerve endings have been reported so far in this experimental model of malnutrition. In summary, early postnatal malnutrition alters the responsiveness of the PAA suggesting damage at the level of the cortical neural elements participating in association processes. REFERENCES 1. DAVISON, A. N., AND J. DOBBING. 1966. Myelination as a vulnerable period in brain development. Br. Med. Bull. 22: 40-44. 2. DOBBING, J. 1968. Vulnerable periods in developing brain. Pages 287-3 16 in A. N. DAVISON AND J. DOBBING, Eds., Applied Neurochemistry. Oxford Press, Oxford. 3. GAMBETTI, P., L. A. GAMBETTI, N. RIZZUTO, B. SHAFER, AND L. PFAFF. 1974. Synapses and malnutrition: quantitative ultrastructural study of rat cerebral cortex. Exp. Neural. 43: 464-473.
HERNANDEZ, A., AND H. I%REZ. 1981. The strength-duration function in the evocation of direct cortical responses. Int. J. Neurosci. 12: 29-32. 5. MONCKEBERG, F. 1969. Malnutrition and mental behavior. Nutr. Rev. 27: 191-193. 6. MORGANE, P. J., M. MILLER, T. KEMPER, W. STERN, W. FORBES,R. HALL, J. BRONZINO, J. KKSANE, E. HA~RYLE~KX, AND 0. RESNICK. 1978. The effectsof protein mahrutrition on the developing central nervous system in the rat. Neurosci. Biobehav. Rev. 2: 1374.
230.
PEREZ ET AL.
244 7.
J. W., AND S. OCHS. 197 1. Occlusive behavior of the negative wave direct cortical response (DCR) and single cells in the cortex. J. Neurophysiol. 34: 374-388. 8. ROBINSON,D. L., AND M. GOLDBERG. 1978. Sensory and behavioral properties of neurons in posterior parietal cortex of awake trained monkey. Fed. Proc. 37: 2258-226 1. 9. SCHERRER,J., AND Y. BLJRNOD. 1978. Some electrophysiological data about neocortical association areas. Pages 393-405 in M. A. BRAZIER AND H. PETSCHE, Eds., Architecfonics of the Cerebral Cortex. Raven Press, New York. 10. SOTO MOYANO, R., S. Ruiz, H. PEREZ, R. CARRILLO, AND A. HERNANDEZ. 1981. Effect of prenatal malnutrition on cortical reactivity of the rat parietal association area. Int. J. Neurosci. 13: 99-102. 11. STERN, W. C., M. MILLER, W. B. FORBES,P. J. MORGANE, AND 0. RESNICK. 1975. Ontogeny of the levels of biogenic amines in various parts of the brain and peripheral tissues in normal and protein malnourished rats. Exp. Neural. 49: 3 14-326. PHILLIPS,