Genistein prevents the decrease in ganglioside levels induced by amyloid-beta in the frontal cortex of rats.

OBJECTIVES: In this study, an in vivo model of Aß toxicity was used to investigate the effects of this peptide and the treatment with genistein on the lipid composition (gangliosides, phospholipids and cholesterol) in the frontal cortex of rats. METHODS: Male Wistar rats received bilateral intracerebroventricular infusions of Aß1-42 (2 nmol) and genistein 10 mg/kg orally for 10 days. Frontal cortex was homogenized with chloroform:methanol for lipid extraction and ganglioside, phospholipid and cholesterol levels were evaluated. RESULTS: The Aß-infused animals showed a significant decrease in ganglioside concentration and relative reduction of GD1b and GQ1b species. Treatment with genistein prevented the decrease in ganglioside levels. Phospholipid and cholesterol contents did not show significant differences. DISCUSSION: Considering the roles of gangliosides on neuronal function, findings described here can contribute to the knowledge of the potential neuroprotective mechanisms of genistein against Aß-induced alterations in the frontal cortex of rats and provide a novel view in the multifaceted scenario associated with its beneficial effects.

Grape juice increases the BDNF levels but not alter the S100B levels in hippocampus and frontal cortex from male Wistar Rats.

Several studies have shown that a high consumption of vegetables and fruits is consistently associated with a low risk of oxidative stress-induced diseases, which includes some degenerative diseases such as amyotrophic lateral sclerosis, Alzheimer and Parkinson. Therefore, the objective of this study is to verify the effects of conventional and organic grape juice in the modulation of the neurotrophic factor (BDNF) and astrocytic markers protein (S100B) in hippocampus and frontal cortex of Wistar rats. In this study, 24 male Wistar rats were divided into three groups. To the first one, it was given organic purple grape juice; to the second, conventional grape juice, while the last one received only saline. After 30 days, all rats were sacrificed and hippocampus and frontal cortex were dissected. The animals that received organic and conventional grape juice showed, in frontal cortex, an elevated BNDF levels in relation to saline group. However, S100B levels did not change. These results showed that grape juices are able to modulate important marker in brain tissue, and could be an important factor to prevent brain diseases.

Grape juice increases the BDNF levels but not alter the S100B levels in hippocampus and frontal cortex from male Wistar Rats

ABSTRACT Several studies have shown that a high consumption of vegetables and fruits is consistently associated with a low risk of oxidative stress-induced diseases, which includes some degenerative diseases such as amyotrophic lateral sclerosis, Alzheimer and Parkinson. Therefore, the objective of this study is to verify the effects of conventional and organic grape juice in the modulation of the neurotrophic factor (BDNF) and astrocytic markers protein (S100B) in hippocampus and frontal cortex of Wistar rats. In this study, 24 male Wistar rats were divided into three groups. To the first one, it was given organic purple grape juice; to the second, conventional grape juice, while the last one received only saline. After 30 days, all rats were sacrificed and hippocampus and frontal cortex were dissected. The animals that received organic and conventional grape juice showed, in frontal cortex, an elevated BNDF levels in relation to saline group. However, S100B levels did not change. These results showed that grape juices are able to modulate important marker in brain tissue, and could be an important factor to prevent brain diseases.

A high-fat diet decreases GABA concentration in the frontal cortex and hippocampus of rats.

BACKGROUND: It has been proposed that the γ-aminobutyric acid (GABA) plays a key role in the regulation of food intake and body weight by controlling the excitability, plasticity and the synchronization of neuronal activity in the frontal cortex (FC). It has been also proposed that the high-fat diet (HFD) could disturb the metabolism of glutamate and consequently the GABA levels, but the mechanism is not yet clearly understood. Therefore, the aim of this study was to investigate the effect of a HFD on the GABA levels in the FC and hippocampus of rats. RESULTS: The HFD significantly increased weight gain and blood glucose levels, whereas decreased the GABA levels in the FC and hippocampus compared with standard diet-fed rats. CONCLUSIONS: HFD decreases GABA levels in the FC and hippocampus of rat, which likely disrupts the GABAergic inhibitory processes, underlying feeding behavior.

A high-fat diet decreases GABA concentration in the frontal cortex and hippocampus of rats

BACKGROUND: It has been proposed that the γ-aminobutyric acid (GABA) plays a key role in the regulation of food intake and body weight by controlling the excitability, plasticity and the synchronization of neuronal activity in the frontal cortex (FC). It has been also proposed that the high-fat diet (HFD) could disturb the metabolism of glutamate and consequently the GABA levels, but the mechanism is not yet clearly understood. Therefore, the aim of this study was to investigate the effect of a HFD on the GABA levels in the FC and hippocampus of rats. RESULTS: The HFD significantly increased weight gain and blood glucose levels, whereas decreased the GABA levels in the FC and hippocampus compared with standard diet-fed rats. CONCLUSIONS: HFD decreases GABA levels in the FC and hippocampus of rat, which likely disrupts the GABAergic inhibitory processes, underlying feeding behavior.

Central fatigue induced by losartan involves brain serotonin and dopamine content.

PURPOSE: To investigate the influence of angiotensin II (Ang II) AT1 receptors blockade on central fatigue induced by brain content of serotonin (5-HT) and dopamine (DA) during exercise. METHODS: Losartan (Los) was intracerebroventricularly injected in rats before running until fatigue (n = 6 per group). At fatigue, brains were quickly removed for measurement of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), DA, and 3,4-dihydroxyphenylacetic acid by high-pressure liquid chromatography in the preoptic area, hypothalamus, hippocampus, and frontal cortex. RESULTS: Intracerebroventricular injection of Los increased 5-HT content in the preoptic area and hypothalamus. Such results correlated positively with body heating rate and inversely with time to fatigue. On the other hand, time to fatigue was directly correlated with the diminished concentration of 5-HT in the hippocampus of Los rats. Although the levels of DA were not affected by Los treatment during exercise in any of the brain areas studied, a higher 5-HT/DA ratio was seen in the hypothalamus of Los animals. This higher hypothalamic 5-HT/DA ratio correlated positively with body heating rate and negatively with time to fatigue. CONCLUSIONS: Our results show that central fatigue due to hyperthermia and increased body heating rate induced by central Ang II AT1 receptor blockade in exercising rats is related with higher 5-HT content in the preoptic area and hypothalamus as well as with decreased levels of this neurotransmitter in the hippocampus. Furthermore, the interaction between 5-HT and DA within the hypothalamus seems to contribute to hyperthermia and premature central fatigue after angiotensinergic inhibition.

Distribution of somatostatin immunoreactivity in the brain of the snake Bothrops jararaca.

The distribution of perikarya and fibers containing somatostatin was studied in the brain of the snake Bothrops jararaca by means of immunohistochemistry using an antiserum against synthetic somatostatin. Immunoreactive perikarya and fibers were localized in telencephalic, diencephalic and mesencephalic areas. In the telencephalon, numerous immunoreactive perikarya were found in the medial, dorsomedial, dorsal and lateral cortex, mainly in the deep plexiform layer, less so in the cellular layer, but not in the superficial plexiform layer. Immunoreactive perikarya were also observed in the dorsal ventricular ridge, the nucleus of the diagonal band of Broca, amygdaloid complex, septum and lamina terminalis. In the diencephalon, labelled cells were observed in the paraventricular, periventricular hypothalamic and in the recessus infundibular nuclei. In the mesencephalon, immunoreactive perikarya were seen in the mesencephalic reticular formation, reticular nucleus of the isthmus and torus semicircularis. Labelled fibers ran along the diencephalic floor and the inner zone of the median eminence, and ended in the neural lobe of the hypophysis. Other fibers were observed in the outer zone of the median eminence close to the portal vessels and in the septum, lamina terminalis, retrochiasmatic nucleus, deep layers of the tectum, periventricular gray and granular layer of the cerebellum. Our data suggest that somatostatin may function as a mediator of adenohypophysial secretion as well as neurotransmitter and/or neuromodulator which can regulate the neurohypophysial peptides in the snake B. jararaca.

Evidence for changes in brain enkephalin contents associated to male rat sexual activity.

Indirect evidence suggests that ejaculation might activate endogenous opioid systems, which exert an inhibitory influence on male rat sexual behaviour. The objective of the present study was to search for putative long-term changes in the contents of immunoreactive (IR) Met-enkephalin (IR-Met), Leu-enkephalin (IR-Leu) and opioid octapeptide Met--Arg(6)--Gly(7)--Leu(8) (IR-Oct) in specific brain areas, after the execution of different amounts of sexual activity. Additionally, basal contents of these enkephalins were compared between sexually active (SA) and persistent sexually inactive (SI) rats. Immunoreactivity to enkephalins was determined by radioimmunoanalysis, in the frontal cortex, the hypothalamus and midbrain of SA and SI rats, as well as 24 or 48 h after males had one ejaculation or copulated to exhaustion. Twenty-four hours after sexual activity, there was a generalised increase in enkephalin contents that returned to control values at the 48 h measurement in all brain areas, but the hypothalamus, where IR-Met and IR-Oct remained elevated. No differences in the magnitude of the changes were found between rats that ejaculated once and sexually satiated males. IR-Oct concentration in the hypothalamus of SI rats appeared significantly higher than in SA animals, with no differences in IR-Met and IR-Leu. Results give direct evidence of the activation of endogenous opioid systems by male rat sexual activity. The occurrence of long lasting increases in the contents of IR-Met and IR-Oct in the hypothalamus of rats that copulated was detected. Finally, an intrinsically elevated octapeptide concentration in the hypothalamus of SI rats was found.

Partial characterization of endogenous modulators of muscarinic acetylcholine receptors in human frontal cortex.

A soluble fraction from human frontal cortex with molecular weight less than 10 kD was tested for the presence of endogenous substances capable of modulating the [3H]-QNB binding to crude P1 + P2 fractions from the same region. The soluble fraction was able to decrease [3H]-QNB binding in a dose-response manner with an IC50 of about 30 micrograms/ml. The effect appeared to be noncompetitive in nature, since Bmax but not Kd was significantly affected; however, in some specimens a biphasic profile, with an initial inhibition of 88-90% of [3H]-QNB binding and 50-60% ulterior binding recuperation was also found. The modulator appeared to have a molecular weight less than 10,000 Daltons and was heat and trypsin resistant. These results point out the existence of an endogenous factor, which could be heterogeneous in regard to its molecular nature or to its action sites.

Allopregnanolone-induced modification of presynaptic basal and K+-induced [3H]-norepinephrine efflux from rat cortical slices during the estrous cycle.

Superfused frontal slices of cerebral cortex were preloaded with [3H]-norepinephrine ([3H]NE). Basal [3H]NE efflux and K+-induced [3H]NE release were studied during the estrous cycle and in the presence of neurosteroids. Basal [3H]NE efflux showed estrous cycle-related variations, with lowest values found during estrus and diestrus II. Allopregnanolone (10(-9) M) potentiated basal [3H]NE efflux from the 1st minute of its application; the effect of the steroid was still present after 20 min. This effect was also dependent upon the estrous cycle, since basal [3H]NE efflux was mainly increased during estrus diestrus I, and to a lesser degree only during proestrus. During diestrus II and after ovariectomy, basal [3H]NE efflux was no longer affected by the neurosteroid. In the presence of yohimbine (10(-6) M), the effect of allopregnanolone on basal efflux was potentiated only during the first 3 min but vanished thereafter. Allopregnanolone (10(-9) M) potentiated the K+-induced [3H]NE release during estrus, but pregnenolone (10(-9) M) was ineffective, suggesting specificity of the neurosteroid. Yohimbine (10(-6) M) also potentiated K+-induced [3H]NE release. When applied simultaneously with allopregnanolone (10(-9) M), a potentiating effect on [3H]NE release was observed. The present results suggest that allopregnanolone is a neurosteroid able to modulate norepinephrine release in the cerebral cortex in an estrous cycle-dependent manner, and that the effect could involve noradrenergic alpha-2 receptors.

Brain thyrotropin-releasing hormone content varies through amygdaloid kindling development according to afterdischarge frequency and propagation.

PURPOSE: Thyrotropin-releasing hormone (TRH), present in extra hypothalamic brain areas, has been proposed to have neuromodulatory functions and to be susceptible to change by electrical stimulation paradigms. We measured TRH concentrations of several brain areas during kindling development before its establishment and determined whether the changes detected in TRH levels were related to the behavioral stages of kindling, the number of stimulations required to reach these stages and, with the electrophysiological parameters characteristic of this paradigm (amygdaloid afterdischarge (AD) frequency, duration, and propagation). METHODS: Male Wistar rats were implanted stereotaxically with indwelling bipolar electrodes in the basolateral nucleus of the amygdala and with two stainless-steel electrodes epidurally in frontal cortex. Amygdaloid kindling was induced by daily electrical stimulation; AD frequency and duration were recorded and analyzed throughout the development of kindling. TRH was extracted from several regions and quantified by radioimmunoassay (RIA). RESULTS: Modifications in TRH concentrations were detected, depending on the region assayed, from stage II of kindling. A positive correlation was noted between the levels of TRH and the frequency and propagation of AD, but not with the number of stimulations. The rate of change in TRH concentration in relation to AD frequency or duration was highest in frontal cortex followed by hippocampus and amygdala. CONCLUSIONS: A graded response was noted in the increase in TRH concentration dependent on the increase of AD frequency and propagation. The rate of response correlated with the region's epileptogenic susceptibility.

Similar effects of glycine, zinc and an oxidizing agent on [3H]dizocilpine binding to the N-methyl-D-aspartate receptor in neocortical tissue from suicide victims and controls.

This study used [3H]dizocilpine (MK-801) binding to the N-methyl-D-aspartate (NMDA) receptor to examine glycine, redox and zinc modulatory sites in membranes derived from the frontal and parietal cortex of control subjects (n = 8) and suicide victims (n = 6). [3H]dizocilpine binding in the presence of glutamate and glutamate plus glycine was similar in control and suicide subjects. The sulphydryl redox site was assessed using the oxidizing agent 5,5'-dithio-bis (2-nitrobenzoic acid), which inhibited binding in a dose-dependent fashion. Both redox and zinc sites were unaffected in the frontal and parietal cortex of suicide victims. These data indicate that the NMDA receptor and its glycine, redox and zinc subsites are preserved in the neocortex of suicide victims.