Effects of fish oil on the central nervous system: a new potential antidepressant?

In the last 100 years major depression has increased worldwide. In this study we provided coconut fat (CF, rich in saturated fatty acids) or fish oil (FO, rich in n-3 polyunsaturated fatty acids) to female rats throughout pregnancy and lactation and then to their offspring post-weaning and examined lipid brain profile and the possible effect of FO as antidepressant agent in the offspring in adulthood (F1). Rats were submitted to forced swimming test, elevated plus maze, Morris water maze and open field. Peroxidation rate in the cerebral cortex and hippocampus were measured. Docosahexaenoic acid (DHA) concentration in dam's milk, eicosapentaenoic acid (EPA) and DHA concentration in hippocampus and cerebral cortex from F1 rats FO supplemented increased significantly when compared to control (C) and CF rats. Arachidonic acid/EPA ratio in the cerebral cortex and hippocampus decreased in rats submitted to forced swimming test. Peroxidation rate were not different between the groups. Immobility time in the forced swimming test in FO group was reduced (p < 0.01) when compared to C and CF rats. We conclude that lifelong intake of FO was able to induce an antidepressant effect with EPA and DHA concentration increased in the cerebral cortex and hippocampus.

Superoxide dismutase, glutathione peroxidase activities and the hydroperoxide concentration are modified in the hippocampus of epileptic rats.

The relationship between free radical and scavenger enzymes has been found in the epileptic phenomena and reactive oxygen species have been implicated in seizure-induced neurodegeneration. Using the epilepsy model obtained by systemic administration of pilocarpine (PILO) in rats, we investigated the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities as well as the hydroperoxide (HPx) concentration in the hippocampus of rats during status epilepticus (SE), silent and chronic periods. The enzyme activities as well as the HPx concentration were measured using spectrophotometric methods and the results compared to values obtained from saline-treated animals. The SOD activity decreased after long-lasting SE period and during the chronic phase. In addition, HPx levels increased in same periods whereas the GPx activity increased only in the hippocampus of animals submitted to 1 h of SE. Animals presenting partial seizures, those submitted to 5 h of SE and animals from the silent period (seizure free) showed normal levels of SOD, GPx and HPx. These results show a direct evidence of lipid peroxidation during seizure activity that could be responsible for neuronal damage in the hippocampus of rats, during the establishment of PILO model of epilepsy.

Selective alterations of glycosaminoglycans synthesis and proteoglycan expression in rat cortex and hippocampus in pilocarpine-induced epilepsy.

Proteoglycans and glycosaminoglycans are elements of matrix. In the nervous system, glycosaminoglycans modulate neurite outgrowth and are co-receptors for growth factors playing a crucial role in cell differentiation and synaptogenesis. The receptor of protein tyrosine phosphatase beta (RPTPbeta) is a chondroitin sulphate proteoglycan which plays an important role in neural morphogenesis and axon guidance mechanisms. Pilocarpine-treated rats present status epilepticus, which is followed by a seizure-free period (silent), by a period of spontaneous recurrent seizures (chronic), and the hippocampus of these animals exhibits cell loss and mossy fiber sprouting. Thus, the synthesis of heparan sulphate and chondroitin sulphate and the time course of RPTPbeta immunoreactivity were studied in the hippocampus and cerebral cortex during these phases of pilocarpine-induced epilepsy. The results showed decreased synthesis of heparan sulphate during the acute phase and an increased synthesis of chondroitin sulphate during the silent period in the cortex and hippocampus. In control rats RPTPbeta immunoreactivity was detected only in glial cells. After 6 h of status epilepticus the RPTPbeta immunoreactivity was no longer detectable in the glial cells in both tissues and intense staining became evident in the matrix, surrounding CA3 and dentate gyrus and piriform cortex neurones. In the silent and chronic periods RPTPbeta immunoreactivity was mainly detected in neuronal somata and fibers of neurones of hippocampus and cortex. These changes show a selective variation of synthesis and expression of glycosaminoglycans and RPTPbeta in relation to epilepsy suggesting a molecular interplay between glia and neurones during seizures.

Profile of prostaglandin levels in the rat hippocampus in pilocarpine model of epilepsy.

Pilocarpine (PILO) administered to rats acutely induces status epilepticus (acute period), which is followed by a transient seizure-free period (silent period), and finally by a chronic phase of spontaneous recurrent seizures (chronic period, SRS) that lasts for the rest of animal's life. Hippocampal neurochemical changes following PILO administration include alteration in monoamines and amino acids content during all phases of this epilepsy model. The present work was delineated to study the content of prostaglandins (PG) levels in hippocampus during the three phases of this model. The levels of PG E2, PG F2 alpha and PG D2 were measured by radioimmunoassay 1 h after PILO, 5 h after PILO, during the silent period, and interictally into the chronic period. The results show, in hippocampus of rats, increase of PG F2 alpha and PG D2 during status epilepticus, increase of PG D2 during the silent period and increase of PG E2 and PG D2 during the chronic phase, when compared with control group. These changes match previously reported alteration in monoamines and amino acid levels, showing that altered neurotransmission is accompanied by changes in second messengers and enzyme activity related to PG production during all phases of the epilepsy model.