Different protocols of physical exercise produce different effects on synaptic and structural proteins in motor areas of the rat brain

The plastic brain responses generated by the training with acrobatic exercise (AE) and with treadmill exercise (TE) may be different. We evaluated the protein expression of synapsin I (SYS), synaptophysin (SYP), microtubule-associated protein 2 (MAP2) and neurofilaments (NF) by immunohistochemistry and Western blotting in the motor cortex, striatum and cerebellum of rats subjected to TE and AE. Young adult male Wistar rats were divided into 3 groups: sedentary (Sed) (n=15), TE (n=20) and AE (n=20). The rats were trained 3 days/week for 4 weeks on a treadmill at 0.6 km/h, 40 min/day (TE), or moved through a circuit of obstacles 5 times/day (AE). The rats from the TE group exhibited a significant increase of SYS and SYP in the motor cortex, of NF68, SYS and SYP in the striatum, and of MAP2, NF and SYS in the cerebellum, whereas NF was decreased in the motor cortex and the molecular layer of the cerebellar cortex. On the other hand, the rats from the AE group showed a significant increase of MAP2 and SYP in the motor cortex, of all four proteins in the striatum, and of SYS in the cerebellum. In conclusion, AE induced changes in the expression of synaptic and structural proteins mainly in the motor cortex and striatum, which may underlie part of the learning of complex motor tasks. TE, on the other hand, promoted more robust changes of structural proteins in all three regions, especially in the cerebellum, which is involved in learned and automatic tasks. (C) 2012 Elsevier B.V. All rights reserved.

The endocannabinoid and endovanilloid systems interact in the rat prelimbic medial prefrontal cortex to control anxiety-like behavior

Cannabinoid receptor 1 (CB1) agonists usually induce dose-dependent biphasic effects on anxiety-related responses. Low doses induce anxiolytic-like effects, whereas high doses are ineffective or anxiogenic, probably due to activation of Transient Receptor Potential Vanilloid Type 1 (TRPV1) channels. In this study we have investigated this hypothesis by verifying the effects of the CB1/TRPV1 agonist ACEA injected into the prelimbic medial prefrontal cortex (PL) and the participation of endocannabinoids in the anxiolytic-like responses induced by TRPV1 antagonism, using the elevated plus-maze (EPM) and the Vogel conflict test (VCT). Moreover, we verified the expression of these receptors in the PL by double labeling immunofluorescence. ACEA induced anxiolytic-like effect in the intermediate dose, which was attenuated by previous injection of AM251, a CB1 receptor antagonist. The higher and ineffective ACEA dose caused anxiogenic- and anxiolytic-like effects, when injected after AM251 or the TRPV1 antagonist 6-iodonordihydrocapsaicin (6-I-CPS), respectively. Higher dose of 6-I-CPS induced anxiolytic-like effects both in the EPM and the VCT, which were prevented by previous administration of AM251. In addition, immunofluorescence showed that CB1 and TRPV1 receptors are closely located in the PL These results indicate that the endocannabinoid and endovanilloid systems interact in the PL to control anxiety-like behavior. (C) 2012 Elsevier Ltd. All rights reserved.

Experimental hyperprolinemia induces mild oxidative stress, metabolic changes, and tissue adaptation in rat liver

The present study investigated the effects of chronic hyperprolinemia on oxidative and metabolic status in liver and serum of rats. Wistar rats received daily subcutaneous injections of proline from their 6th to 28th day of life. Twelve hours after the last injection the rats were sacrificed and liver and serum were collected. Results showed that hyperprolinemia induced a significant reduction in total antioxidant potential and thiobarbituric acid-reactive substances. The activities of the antioxidant enzymes catalase and superoxide dismutase were significantly increased after chronic proline administration, while glutathione (GSH) peroxidase activity, dichlorofluorescin oxidation, GSH, sulfhydryl, and carbonyl content remained unaltered. Histological analyses of the liver revealed that proline treatment induced changes of the hepatic microarchitecture and increased the number of inflammatory cells and the glycogen content. Biochemical determination also demonstrated an increase in glycogen concentration, as well as a higher synthesis of glycogen in liver of hyperprolinemic rats. Regarding to hepatic metabolism, it was observed an increase on glucose oxidation and a decrease on lipid synthesis from glucose. However, hepatic lipid content and serum glucose levels were not changed. Proline administration did not alter the aminotransferases activities and serum markers of hepatic injury. Our findings suggest that hyperprolinemia alters the liver homeostasis possibly by induction of a mild degree of oxidative stress and metabolic changes. The hepatic alterations caused by proline probably do not implicate in substantial hepatic tissue damage, but rather demonstrate a process of adaptation of this tissue to oxidative stress. However, the biological significance of these findings requires additional investigation. J. Cell. Biochem. 113: 174183, 2012. (C) 2011 Wiley Periodicals, Inc.

mu(1)- and 5-HT1-dependent mechanisms in the anterior pretectal nucleus mediate the antinociceptive effects of retrosplenial cortex stimulation in rats

Aim: This study examines if injection of cobalt chloride (CoCl2) or antagonists of muscarinic cholinergic (atropine), mu(1)-opioid (naloxonazine) or 5-HT1 serotonergic (methiothepin) receptors into the dorsal or ventral portions of the anterior pretectal nucleus (APtN) alters the antinociceptive effects of stimulating the retrosplenial cortex (RSC) in rats. Main method: Changes in the nociceptive threshold were evaluated using the tail flick or incision pain tests in rats that were electrically stimulated at the RSC after the injection of saline, CoCl2 (1 mM, 0.10 mu L) or antagonists into the dorsal or ventral APtN. Key findings: The injection of CoCl2, naloxonazine (5 mu g/0.10 mu L) or methiothepin (3 mu g/0.10 mu L) into the dorsal APtN reduced the stimulation-produced antinociception from the RSC in the rat tail flick test. Reduction of incision pain was observed following stimulation of the RSC after the injection of the same substances into the ventral APtN. The injection of atropine (10 ng/0.10 mu L) or ketanserine (5 mu g/0.10 mu L) into the dorsal or ventral APtN was ineffective against the antinociception resulting from RSC stimulation. Significance: mu(1)-opioid- and 5-HT1-expressing neurons and cell processes in dorsal and ventral APtN are both implicated in the mediation of stimulation-produced antinociception from the RSC in the rat tail flick and incision pain tests, respectively. (c) 2012 Elsevier Inc. All rights reserved.

PARAVENTRICULAR AND SUPRAOPTIC NUCLEI OF THE HYPOTHALAMUS MEDIATE CARDIOVASCULAR RESPONSES EVOKED BY THE MICROINJECTION OF NORADRENALINE INTO THE MEDIAL AMYGDALOID NUCLEUS OF THE RAT BRAIN

The medial amygdaloid nucleus (MeA) is a part of the limbic system and is involved in cardiovascular modulation. We previously reported that microinjection of noradrenaline (NA) into the MeA of unanesthetized rats caused pressor and bradycardiac responses, which were mediated by acute vasopressin release into the systemic circulation. In the present study, we tested the possible involvement of magnocellular neurons of the paraventricular (PVN) and/or supraoptic (SON) of the hypothalamus that synthesize vasopressin in the cardiovascular pathway activated by the microinjection of NA into the MeA. Pressor and bradycardiac responses to the microinjection of NA (27 nmol/100 nL) into the MeA were blocked by pretreatment of either the PVN or the SON with cobalt chloride (CoCl2, 1 mM/100 nL), thus indicating that both hypothalamic nuclei mediate the cardiovascular responses evoked by microinjection of NA Into the MeA. Our results suggest that the pressor and bradycardiac response caused by the microinjection of NA into the MeA is mediated by magnocellular neurons in both the PVN and SON. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Acute cocaine treatment increases thimet oligopeptidase in the striatum of rat brain

Many studies indicate that thimet oligopeptidase (EC3.4.24.15; TOP) can be implicated in the metabolism of bioactive peptides, including dynorphin 1-8, alpha-neoendorphin, beta-neoendorphin and GnRH. Furthermore, the higher levels of this peptidase are found in neuroendocrine tissue and testis. In the present study, we have evaluated the effect of acute cocaine administration in male rats on TOP specific activity and mRNA levels in prosencephalic brain areas related with the reward circuitry; ventral striatum, hippocampus, and frontal cortex. No significant differences on TOP specific activity were detected in the hippocampus and frontal cortex of cocaine treated animals compared to control vehicle group. However, a significant increase in activity was observed in the ventral striatum of cocaine treated-rats. The increase occurred in both, TOP specific activity and TOP relative mRNA amount determined by real time RT-PCR. As TOP can be implicated in the processing of many neuropeptides, and previous studies have shown that cocaine also alters the gene expression of proenkephalin and prodynorphin in the striatum, the present findings suggest that TOP changes in the brain could play important role in the balance of neuropeptide level correlated with cocaine effects. (C) 2012 Elsevier Inc. All rights reserved.

Chronic infusion of amyloid-β peptide and sustained attention altered α7 nicotinic receptor density in the rat brain

It is already known that progressive degeneration of cholinergic neurons in brain areas such as the hippocampus and the cortex leads to memory deficits, as observed in Alzheimer's disease. This work verified the effects of the infusion of amyloid-beta (A beta) peptide associated to an attentional rehearsal on the density of alpha 7 nicotinic cholinergic receptor (nAChR) in the brain of male Wistar rats. Animals received intracerebroventricular infusion of A beta or vehicle (control - C) and their attention was stimulated weekly (Stimulated A beta group: S-A beta and Stimulated Control group: SC) or not (Non-Stimulated A beta group: N-SA beta and Non-Stimulated Control group: N-SC), using an active avoidance apparatus. Conditioned avoidance responses (CAR) were registered. Chronic infusion of A beta caused a 37% reduction in CAR for N-SA beta. In S-A beta, this reduction was not observed. At the end, brains were extracted and autoradiography for alpha 7 nAChR was conducted using [I-125]-alpha-bungarotoxin. There was an increase in alpha 7 density in hippocampus, cortex and amygdala of SA beta animals, together with the memory preservation. In recent findings from our lab using mice infused with A beta and the alpha 7 antagonist methyllycaconitine, and stimulated weekly in the same apparatus, it was observed that memory maintenance was abolished. So, the increase in alpha 7 density in brain areas related to memory might be related to a participation of this receptor in the long-lasting change in synaptic plasticity, which is important to improve and maintain memory consolidation.