Hernán Pérez

Head size and intelligence, learning, nutritional status and brain development Head, IQ, learning, nutrition and brain

This multifactorial study investigates the interrelationships between head circumference (HC) and intellectual quotient (IQ), learning, nutritional status and brain development in Chilean school-age children graduating from high school, of both sexes and with high and low IQ and socio-economic strata (SES). The sample consisted of 96 right-handed healthy students (mean age 18.0 +/- 0.9 years) born at term. HC was measured both in the children and their parents and was expressed as Z-score (Z-HC). In children, IQ was determined by means of the Wechsler Intelligence Scale for Adults-Revised (WAIS-R), scholastic achievement (SA) through the standard Spanish language and mathematics tests and the academic aptitude test (AAT) score, nutritional status was assessed through anthropometric indicators, brain development was determined by magnetic resonance imaging (MRI) and SES applying the Graffar modified method. Results showed that microcephalic children (Z-HC < or = 2 S.D.) had significantly lower values mainly for brain volume (BV), parental Z-HC, IQ, SA, AAT, birth length (BL) and a significantly higher incidence of undernutrition in the first year of life compared with their macrocephalic peers (Z-HC > 2S.D.). Multiple regression analysis revealed that BV, parental Z-HC and BL were the independent variables with the greatest explanatory power for childs Z-HC variance (r(2) = 0.727). These findings confirm the hypothesis formulated in this study: (1) independently of age, sex and SES, brain parameters, parental HC and prenatal nutritional indicators are the most important independent variables that determine HC and (2) microcephalic children present multiple disorders not only related to BV but also to IQ, SA and nutritional background.

Long-term effects of severe undernutrition during the first year of life on brain development and learning in Chilean high-school graduates.

The objective of this study was to assess the relative impact of undernutrition during the first year of life on brain development, intellectual quotient (IQ), and scholastic achievement (SA) of poor Chilean high-school graduates (mean age = 18.3 +/- 0.9 y). A comparative study of two groups of high-school graduates from a low socioeconomic stratum was carried out. The undernourished group (n = 16), who had suffered from severe undernutrition during the first year of life, was compared with the non-undernourished group (n = 16). The final sample consisted of 32 right-handed high-school graduate students born at term who had no history of alcoholism or symptoms of brain damage, epilepsy, or heart disease and whose mothers had no history of smoking, alcoholism, or drug intake before and during pregnancy. Socioeconomic status was measured by using Graffars modified method. Birth weight was used as the prenatal nutritional status index, and postnatal nutritional status was assessed by the body mass index, Z score for head circumference, and brachial anthropometry. IQ was determined with the Wechsler Intelligence Scale for Adults, and SA was determined with test in language and mathematics with the academic aptitude test. Brain development was evaluated by magnetic resonance imaging. Statistical analysis included variance tests, Scheffes test for comparison of means, correlation, and multiple regression. Maternal schooling, brain volume, and undernutrition were the independent variables, with the greatest explanatory power in IQ variance (r(2) = 0.714). Only IQ explained SA variance (r(2) = 0.860); IQ, corpus callosum length, anteroposterior diameter, and maternal schooling were the independent variables, with the greatest explanatory power in the academic aptitude test variance (r(2) = 0.949). Results show that the long-term effects of malnutrition at an early age may affect brain development, IQ, and SA in school-age children. These findings are useful for nutrition and educational planning.

Nutritional status, brain development and scholastic achievement of Chilean high-school graduates from high and low intellectual quotient and socio-economic status

The objective of the present study was to investigate the inter-relationships between nutritional status (past and current nutrition), brain development, and scholastic achievement (SA) of Chilean high-school graduates from high and low intellectual quotient (IQ) and socio-economic status (SES) (mean age 18.0 (SD 0.9) years). Results showed that independently of SES, high-school graduates with similar IQ have similar nutritional, brain development and SA variables. Multiple regression analysis between child IQ (dependent variable) and age, sex, SES, brain volume (BV), undernutrition during the first year of life, paternal and maternal IQ (independent variables) revealed that maternal IQ (P<0.0001), BV (P<00387) and severe undernutrition during the first year of life (P<0.0486), were the independent variables with the greatest explanatory power for child IQ variance (r2 0.707), without interaction with age, sex or SES. Child IQ (P<0.0001) was the only independent variable that explained both SA variance (r2 0.848) and academic aptitude test variance (r2 0.876) without interaction with age, sex or SES. These results confirm the hypotheses formulated for this study that: (1) independently of SES, high-school graduates with similar IQ have similar variables of nutritional status, brain development and SA; (2) past nutritional status, brain development, child IQ and SA are strongly and significantly inter-related. These findings are relevant in explaining the complex interactions between variables that affect IQ and SA and can be useful for nutritional and educational planning.

Effect of ketamine on spinal cord nociceptive transmission in normal and monoarthritic rats.

The effects of systemically and intrathecally administered ketamine on spinal wind-up of normal and monoarthritic rats were studied by using C-fiber reflex responses evoked by repetitive (0.6 Hz) electric stimulation. Both systemic and intrathecal ketamine induced dose-dependent depression of wind-up activity in normal rats, as revealed by the dose-related inhibitory effects of the drug. At the same intraperitoneal doses, ketamine produced a greater inhibitory effect on wind-up activity of monoarthritic rats, compared to normal animals. The intrathecal administration of ketamine also produced wind-up inhibition, the efficacy being higher in the monoarthritic rats. Results indicate that ketamine depresses spinal wind-up, specially in rats submitted to chronic pain, probably due to its antagonistic properties on dorsal horn NMDA receptors, which play a crucial role in the maintenance of chronic pain.

Mild prenatal protein malnutrition increases α2C‐adrenoceptor density in the cerebral cortex during postnatal life and impairs neocortical long‐term potentiation and visuo‐spatial performance in rats

Mild reduction in the protein content of the mothers diet from 25 to 8% casein, calorically compensated by carbohydrates, does not alter body and brain weights of rat pups at birth, but leads to significant enhancements in the concentration and release of cortical noradrenaline during early postnatal life. Since central noradrenaline and some of its receptors are critically involved in long‐term potentiation (LTP) and memory formation, this study evaluated the effect of mild prenatal protein malnutrition on the α2C‐adrenoceptor density in the frontal and occipital cortices, induction of LTP in the same cortical regions and the visuo‐spatial memory. Pups born from rats fed a 25% casein diet throughout pregnancy served as controls. At day 8 of postnatal age, prenatally malnourished rats showed a threefold increase in neocortical α2C‐adrenoceptor density. At 60 days‐of‐age, α2C‐adrenoceptor density was still elevated in the neocortex, and the animals were unable to maintain neocortical LTP and presented lower visuo‐spatial memory performance. Results suggest that overexpression of neocortical α2C‐adrenoceptors during postnatal life, subsequent to mild prenatal protein malnutrition, could functionally affect the synaptic networks subserving neocortical LTP and visuo‐spatial memory formation.

α2-Adrenoceptor modulation of long-term potentiation elicited in vivo in rat occipital cortex

Pretreatment with the alpha(2)-adrenoceptor agonist clonidine (31.25, 62.5, or 125 microg/kg, i.p.) dose-dependently reduced long-term potentiation (LTP) elicited in vivo in the occipital cortex of anesthetized rats, whereas pretreatment with the alpha(2)-adrenoceptor antagonist yohimbine (0.133, 0.4, or 1.2 mg/kg, i.p.) increased neocortical LTP in a dose-dependent fashion. These effects could be related to the reported disruptive and facilitatory actions induced on memory formation by pretreatment with alpha(2)-adrenoceptor agonists and antagonists, respectively.

Effects of mild protein prenatal malnutrition and subsequent postnatal nutritional rehabilitation on noradrenaline release and neuronal density in the rat occipital cortex

There is evidence that severe malnutrition started during gestation and continued through lactation affects adversely the morphologic development of the neocortex leading to increased neuronal cell packing density and decreased dendritic branching. Nevertheless, the effect of purely mild protein prenatal malnutrition on neocortical development remains rather unexplored. This study evaluates the effects of mild protein prenatal malnutrition (8% casein diet, calorically compensated by carbohydrates) and subsequent postnatal nutritional rehabilitation (25% casein diet) on: (i) the potassium-induced release of [(3)H]-noradrenaline (NA) in occipital cortex slices obtained from 1- and 22-day-old pups; and (ii) the packing density of neurons in lateral, dorso-lateral and dorsal regions of the occipital cortex of 22-day-old pups by using the optical dissector method. The experiments were performed in rats normally fed during gestation and lactation (G(+)L(+)), malnourished during gestation but rehabilitated during lactation (G(-)L(+)) and malnourished during gestation and lactation (G(-)L(-)). At day 1 of age, no significant differences in body and brain weights were observed between prenatally well-nourished and malnourished pups. Nevertheless, at this early age, pups born from mothers submitted to the 8% casein diet had significantly higher cortical net percent NA release than pups born from mothers receiving the 25% casein diet. At weaning (22 days of age) G(-)L(+) rats had, compared to the G(+)L(+) group, similar body weight, brain weight and [(3)H]-NA release values, but significantly higher neuron density scores in the lateral region of the occipital cortex. In contrast, at 22 days of age, G(-)L(-) rats exhibited, compared to G(+)L(+) animals, significant deficits in body and brain weights as well as significant increases in cortical net percent NA release together with enhanced packing density of neurons in the lateral, dorso-lateral and dorsal regions of the occipital cortex. Moreover, in G(-)L(-) animals was not found the laterodorsal histogenetic gradient of neuronal cell packing density observed in G(+)L(+)rats. Results suggest that mild prenatal malnutrition per se is able to induce deleterious effects on cortical neuronal density, in spite of nutritional rehabilitation during lactation, through a mechanism involving central NA hyperactivity during gestation. Prosecution of malnutrition after birth magnifies both neurochemical and morphometric disorders.

Fetal undernutrition induces overexpression of CRH mRNA and CRH protein in hypothalamus and increases CRH and corticosterone in plasma during postnatal life in the rat

Prenatal undernutrition induces a variety of cardiovascular alterations in mammals when adults, including hypertension and hypercortisolism, which are thought to be caused by decreased glucocorticoid feedback control of the hypothalamus-pituitary-adrenal (HPA) axis programmed during fetal life. Hypothalamic CRH seems to be involved in blood pressure elevation of spontaneously hypertensive rats and in primary hypertension of humans, but the influence of prenatal undernutrition on CRH expression has deserved little attention. Here, we studied the expression of both CRH mRNA and CRH protein in the hypothalamus of neonatal and juvenile offspring of rats undernourished during fetal life, as well as the plasma levels of CRH and corticosterone. Prenatal undernutrition of pups was induced by submitting pregnant rats to diet restriction (10g daily of 21% protein standard laboratory diet). Pups born from dams with free access to the standard laboratory diet served as controls. At day 2 of postnatal age, undernourished pups showed lower body and brain weights, but higher plasma CRH and corticosterone than normal pups. At day 40 of age, brain weight was significantly decreased in the undernourished rats, while plasma corticosterone, plasma CRH and systolic pressure were significantly increased in these animals. At days 2 and 40 of postnatal age, increased CRH mRNA expression and CRH concentration were found in the hypothalamus of undernourished rats. Results indicate that, in the rat, prenatal undernutrition led to fetal programming of CRH overexpression, a neuropeptide serving as activating signal to the HPA axis and/or to extrahypothalamic brain regions concerned with cardiovascular regulation.

Medullary responses to chemoreceptor activation are inhibited by locus coeruleus and nucleus raphe magnus.

The effect of electrical and L-glutamate stimulation of the nucleus locus coeruleus (LC) and nucleus raphe magnus (NRM) on multiunit activity evoked in the nucleus tractus solitarius (NTS) by activation of arterial chemoreceptors (15-25 micrograms kg-1 of sodium cyanoborohydride, i.v.) was studied in rats anaesthetized with urethane (1.1 g kg-1 i.p.). Multiunit discharge of NTS neurones in response to cyanide injection was composed by spikes higher than 200 microV and about 10 Hz frequency. Electrical and L-glutamate stimulation of the LC and the NRM significantly reduced the frequency of the cyanide-induced multiunit discharge. The results show that neurones of the NTS with input from arterial chemoreceptors can be inhibited by LC and and NRM cells, suggesting that these nuclei play a role in controlling chemosensory input at the NTS.

Locus coeruleus stimulation modulates olfactory bulb evoked potentials

Field-evoked potentials from the main olfactory bulb in response to stimulation of the olfactory nerve and lateral olfactory tract were measured without and with conditioning stimulation of the locus coeruleus noradrenergic system. The locus coeruleus conditioning stimulus suppressed or inhibited the late components of the olfactory bulb potential evoked by orthodromic olfactory nerve stimulation; this inhibitory effect was suppressed by the microinjection of the alpha-adrenergic blocker prazosin into the olfactory bulb. Results indicate that noradrenergic fibers projecting from the locus coeruleus exert modulatory influences on neuronal networks underlying orthodromic evoked responses in the main olfactory bulb.