Nutritional conditions early in life constitute one environmental factor that can influence brain electrophysiological features. Cortical spreading depression (SD) is a brain electrophysiological phenomenon that can be altered by the early nutritional status of organism. SD-velocity changes were presently studied in young (30-40 days old) and adult (90-120 days) rats suckled in litters formed by 3, 6, or 12 pups (called respectively small (S), medium (M) and large (L) litters). Body weights and SD propagation velocities in the 3 groups varied, respectively in an inverse and direct way, in relation to the litter sizes. The present investigation provides the first systematic description of the effectiveness of favorable and unfavorable lactation conditions (respectively suckling in S and L litters) in altering cortical SD-propagation. The results confirm previous evidence in favor of permanent or at least long-lasting SD-changes associated to the prevailing nutritional status during the period of fast brain development.

Lactating rat dams were submitted to short episodes (1, 2 or 3 weeks) of nutritional restriction by receiving the "regional basic diet" (RBD, with 8% protein) of low-income human populations of Northeast Brazil. Their pups were then studied regarding the developmental effects on body and brain weights. When the rats reached adulthood, cortical susceptibility to the phenomenon of spreading depression (SD) was evaluated by performing electrophysiological recordings on the surface of the cerebral cortex. SD was elicited at 20-min intervals by applying 2% KCl for 1 min to a site on the frontal cortex and its occurrence was monitored at 2 sites in the parietal region by recording the electrocorticogram and the slow potential change of SD. When compared to control rats fed a commercial diet with 23% protein, early malnourished rats showed deficits in body and brain weights (10% to 60% and 3% to 15%, respectively), as well as increases in velocity of SD propagation (10% to 20%). These effects were directly related to the duration of maternal dietary restriction, with pups malnourished for 2 or 3 weeks presenting more intense weight and SD changes than those malnourished for 1 week. The effects of 1-week restrictions on SD were less evident in the pups malnourished during the second week of lactation and were more evident in pups receiving the RBD during the third week. The results indicate that short episodes of early malnutrition during the suckling period can affect body and brain development, as well as the cortical susceptibility to SD during adulthood. The data also suggest that the third week of lactation is the period during which the brain is most sensitive to malnutrition, concerning the effects on SD.

Oxidative stress (OS) has been implicated in the etiology of certain neurodegenerative disorders. Some of these disorders have been associated with unbalanced levels of essential fatty acids (EFA). The response of certain brain regions to OS, however, is not uniform and a selective vulnerability or resilience can occur. In our previous study on rat brains, we observed that a two-generation EFA dietary restriction reduced the number and size of dopaminergic neurons in the substantia nigra (SN) rostro-dorso-medial. To understand whether OS contributes to this effect, we assessed the status of lipid peroxidation (LP) and anti-oxidant markers in both SN and corpus striatum (CS) of rats submitted to this dietary treatment for one (F1) or two (F2) generations. Wistar rats were raised from conception on control or experimental diets containing adequate or reduced levels of linoleic and α-linolenic fatty acids, respectively. LP was measured using the thiobarbituric acid reaction method (TBARS) and the total superoxide dismutase (t-SOD) and catalase (CAT) enzymatic activities were assessed. The experimental diet significantly reduced the docosahexaenoic acid (DHA) levels of SN phospholipids in the F1 (~28%) and F2 (~50%) groups. In F1 adult animals of the experimental group there was no LP in both SN and CS. Consistently, there was a significant increase in the t-SOD activity (p < 0.01) in both regions. In EF2 young animals, degeneration in dopaminergic and non-dopaminergic neurons and a significant increase in LP (p < 0.01) and decrease in the CAT activity (p < 0.001) were detected in the SN, while no inter-group difference was found for these parameters in the CS. Conversely, a significant increase in t-SOD activity (p < 0.05) was detected in the CS of the experimental group compared to the control. The results show that unbalanced EFA dietary levels reduce the redox balance in the SN and reveal mechanisms of resilience in the CS under this stressful condition.

Cortical spreading depression (CSD) propagation was investigated in rats under dietary essential fatty acid (EFA) deficiency over two generations (F1 and F2). Wistar rat dams received diets containing 5% fat either from coconut-oil (EFA-deficient) or soybean-oil (control). F1-pups received their dams' diets until the day of CSD recording (30-40 days or 90-100 days). F2-pups were kept on their F1 dams' diet until 30-40 days. Compared to the controls, the EFA-deficient group had reduced (P < 0.05) body weights in both F1 and F2 conditions. This effect was more conspicuous (P < 0.001) in the F2-animals where brain weight was also reduced (P < 0.05). All EFA-deficient groups displayed lower CSD velocities (P < 0.001) than the corresponding controls. Within the same dietary group and generation, F1 young rats showed higher CSD velocities (P < 0.001) than adults. Data show that EFA deficiency reduces CSD propagation, and this effect is long lasting as it persists up to the second generation.

Tissue distribution of nitric oxide-synthases was investigated in the rat hippocampus and visual cortex under nutritional changes induced by modification of the litter size. Young (30-45-days-old) rats, suckled in litters formed by 3,6 or 12 pups (called small, medium and large litters, respectively), were studied by using nicotine-adenine-dinucleotide phosphate-diaphorase histochemistry (shortly, diaphorase), a simple and robust procedure to characterize tissue distribution of nitric oxide-synthases. We assessed morphometric features of the diaphorase-positive cells in visual cortex, and the neuropil histochemical activity in hippocampal CA1 and dentate gyrus using densitometry analysis. In the large-litter group, the labeled-cell density in white matter of area 17 was higher, as compared to the small-litter group. There was a clear trend, in the large-litter group, to lower values of soma area, dendritic field and branches per neuron, but the differences were not significant. Densitometry analysis of hippocampus revealed a significant increase in the relative neuropil histochemical activity of the dentate gyrus molecular layer in the larger litters, which may be associated to increased compensatory blood flow in the hippocampus. The pathophysiological mechanisms of the observed changes remain to be investigated.