Retinoid-Related Receptor (ROR) alpha mRNA Expression Is Altered in the Brain of Male Mice Lacking All Ligand-Binding Thyroid Hormone Receptor (TR) Isoforms

In the vertebrate brain, the thalamus serves as a relay and integration station for diverse neuronal information en route from the periphery to the cortex. Deficiency of TH during development results in severe cerebral abnormalities similar to those seen in the mouse when the retinoic acid receptor (ROR)α gene is disrupted. To investigate the effect of the thyroid hormone recep-tors (TRs) on RORalpha gene expression, we used intact male mice, in which the genes encoding the α and beta TRs have been deleted. In situ hybridization for RORalpha mRNA revealed that this gene is expressed in specific areas of the brain including the thalamus, pons, cerebellum, cortex, and hippocampus. Our quantitative data showed differences in RORalpha mRNA expression in different subthalamic nuclei between wild-type and knock-out mice. For example, the centromedial nucleus of the thalamus, which plays a role in mediating nociceptive and visceral information from the brainstem to the basal ganglia and cortical regions, has less expression of RORalpha mRNA in the knockout mice (-37%) compared to the wild-type controls. Also, in the dorsal geniculate (+72%) and lateral posterior nuclei (+58%) we found more RORalpha mRNA in dKO as compared to dWT animals. Such differences in RORalpha mRNA expression may play a role in the behavioral alterations resulting from congenital hypothyroidism.

Heart rate variability is associated with amygdala functional connectivity with MPFC across younger and older adults

The ability to regulate emotion is crucial to promote well-being. Evidence suggests that the medial prefrontal cortex (mPFC) and adjacent anterior cingulate (ACC) modulate amygdala activity during emotion regulation. Yet less is known about whether the amygdala-mPFC circuit is linked with regulation of the autonomic nervous system and whether the relationship differs across the adult lifespan. The current study tested the hypothesis that heart rate variability (HRV) reflects the strength of mPFC-amygdala interaction across younger and older adults. We recorded participants’ heart rates at baseline and examined whether baseline HRV was associated with amygdala-mPFC functional connectivity during rest. We found that higher HRV was associated with stronger functional connectivity between the amygdala and the mPFC during rest across younger and older adults. In addition to this age-invariant pattern, there was an age-related change, such that greater HRV was linked with stronger functional connectivity between amygdala and ventrolateral PFC (vlPFC) in younger than in older adults. These results are in line with past evidence that vlPFC is involved in emotion regulation especially in younger adults. Taken together, our results support the neurovisceral integration model and suggest that higher heart rate variability is associated with neural mechanisms that support successful emotional regulation across the adult lifespan.

An Alternative Section Method for Casting and Posterior Laser Welding of Metallic Frameworks for an Implant-Supported Prosthesis

Purpose: The aim of this study was to compare the accuracy of fit of three types of implant-supported frameworks cast in Ni-Cr alloy: specifically, a framework cast as one piece compared to frameworks cast separately in sections to the transverse or the diagonal axis, and later laser welded. Materials and Methods: Three sets of similar implant-supported frameworks were constructed. The first group of six 3-unit implant-supported frameworks were cast as one piece, the second group of six were sectioned in the transverse axis of the pontic region prior to casting, and the last group of six were sectioned in the diagonal axis of the pontic region prior to casting. The sectioned frameworks were positioned in the matrix (10 N(.)cm torque) and laser welded. To evaluate passive fit, readings were made with an optical microscope with both screws tightened and with only one-screw tightened. Data were submitted to ANOVA and Tukey-Kramer`s test (p < 0.05). Results: When both screws were tightened, no differences were found between the three groups (p > 0.05). In the single-screw-tightened test, with readings made opposite to the tightened side, the group cast as one piece (57.02 +/- 33.48 mu m) was significantly different (p < 0.05) from the group sectioned diagonally (18.92 +/- 4.75 mu m) but no different (p > 0.05) from the group transversally sectioned (31.42 +/- 20.68 mu m). On the tightened side, no significant differences were found between the groups (p > 0.05). Conclusions: Results of this study showed that casting diagonally sectioned frameworks lowers misfit levels of prosthetic implant-supported frameworks and also improves the levels of passivity to the same frameworks when compared to structures cast as one piece.

Histomorphometric Evaluation of Bioceramic Molecular Impregnated and Dual Acid-Etched Implant Surfaces in the Human Posterior Maxilla

Background: Physical and bioceramic incorporation surface treatments at the nanometer scale showed higher means of bone-to-implant contact (BIC) and torque values compared with surface topography at the micrometer scale; however, the literature concerning the effect of nanometer scale parameters is sparse. Purpose: The aim of this study was to evaluate the influence of two different implant surfaces on the percentage bone-to-implant contact (BIC%) and bone osteocyte density in the human posterior maxilla after 2 months of unloaded healing. Materials and Methods: The implants utilized presented dual acid-etched (DAE) surface and a bioceramic molecular impregnated treatment (Ossean(R), Intra-Lock International, Boca Raton, FL, USA) serving as control and test, respectively. Ten subjects (59 1 9 years of age) received two implants (one of each surface) during conventional implant surgery in the posterior maxilla. After the non-loaded period of 2 months, the implants and the surrounding tissue were removed by means of a trephine and were non-decalcified processed for ground sectioning and analysis of BIC%, bone density in threaded area (BA%), and osteocyte index (Oi). Results: Two DAE implants were found to be clinically unstable at time of retrieval. Histometric evaluation showed significantly higher BIC% and Oi for the test compared to the control surface (p < .05), and that BA% was not significantly different between groups. Wilcoxon matched pairs test was used to compare the differences of histomorphometric variables between implant surfaces. The significance test was conducted at a 5% level of significance. Conclusion: The histological data suggest that the bioceramic molecular impregnated surface-treated implants positively modulated bone healing at early implantation times compared to the DAE surface.

Synthetic modified N-POMC(1-28) controls in vivo proliferation and blocks apoptosis in rat adrenal cortex

The identity of the pro-opiomelanocortin (POMC)-derived mitogen in the adrenal cortex has been historically controversial. We have used well-established in vivo models, viz., hypophysectomized (Hyp) or dexamethasone (Dex)-treated rats, to study the effect of the synthetic modified peptide N-terminal POMC (N-POMC(1-28)) on DNA synthesis in the adrenal cortex, as assessed by BrdU incorporation and compared with adrenocorticotropic hormone (ACTH). We evaluated the importance of disulfide bridges on proliferation by employing N-POMC(1-28) without disulfide bridges and with methionines replacing cysteines. Acute administration of synthetic modified N-POMC(1-28) distinctly increased DNA synthesis in the zona glomerulosa and zona fasciculata, but not in the zona reticularis in Hyp rats, whereas in Dex-treated rats, this peptide was effective in all adrenal zones. ACTH administration led to an increase of BrdU-positive cells in all adrenal zones irrespective of the depletion of Hyp or Dex-POMC peptides. The use of the ACTH antagonist, ACTH(7-38), confirmed the direct participation of ACTH in proliferation. Two different approaches to measure apoptosis revealed that both peptides similarly exerted a protective effect on all adrenocortical zones, blocking the apoptotic cell death induced by hypophysectomy. Thus, ACTH(1-39) and N-POMC(1-28) have similar actions suggesting that the disulfide bridges are important but not essential. Both peptides seem to be important factors determining adrenocortical cell survival throughout the adrenal cortex, reinforcing the idea that each zone can be renewed from within itself.

Architectonic subdivisions of the amygdalar complex of a primitive marsupial (Didelphis aurita)

The architecture of the amygdaloid complex of a marsupial, the opossum Didelphis aurita, was analyzed using classical stains like Nissl staining and myelin (Gallyas) staining, and enzyme histochemistry for acetylcholinesterase and NADPH-diaphorase. Most of the subdivisions of the amygdaloid complex described in eutherian mammals were identified in the opossum brain. NADPH-diaphorase revealed reactivity in the neuropil of nearly all amygdaloid subdivisions with different intensities, allowing the identification of the medial and lateral subdivisions of the cortical posterior nucleus and the lateral subdivision of the lateral nucleus. The lateral, central, basolateral and basomedial nuclei exhibited acetylcholinesterase positivity, which provided a useful chemoarchitectural criterion for the identification of the anterior basolateral nucleus. Myelin stain allowed the identification of the medial subdivision of the lateral nucleus, and resulted in intense staining of the medial subdivisions of the central nucleus. The medial, posterior, and cortical nuclei, as well as the amygdalopiriform area did not exhibit positivity for myelin staining. On the basis of cyto- and chemoarchitectural criteria, the present study highlights that the opossum amygdaloid complex shares similarities with that of other species, thus supporting the idea that the organization of the amygdala is part of a basic plan conserved through mammalian evolution. (C) 2008 Elsevier Inc. All rights reserved.

The proliferative effect of synthetic N-POMC(1-28) peptides in rat adrenal cortex: A possible role for cyclin E

Modified synthetic N-POMC(1-28) without disulfide bridges has been shown to act as an adrenal mitogen. Cyclins and their inhibitors are the major cell cycle controls, but in the adrenal cortex the effect of ACTH and N-POMC on the expression of these proteins remains unclear. In this work, we evaluate the effect of different synthetic N-POMC peptides on the S-phase of the cell cycle. In addition, we examine the cyclin E expression in rat adrenal cortex. Rats treated with dexamethasone were injected with ACTH and/or synthetic modified N-POMC and/or synthetic N-POMC with disulfide bridges. DNA synthesis was determined by BrdU incorporation and protein expression was analyzed by immunoblotting and immunohistochemistry. The results showed that similarly to modified N-POMC without disulfide bridges, administration of synthetic N-POMC with disulfide bridges and the combination of ACTH and N-POMC promoted an increase of BrdU-positive nuclei in adrenal cortex. However, the proliferative effect of N-POMC was comparable to that of ACTH only in the zona glomerulosa. An increase in cyclin E expression was observed 6 h after N-POMC treatment in the outer fraction of the adrenal cortex, in agreement with immunohistochemical findings in the zona glomerulosa. In summary, the effect of synthetic N-POMC with disulfide bridges was similar to modified synthetic N-POMC, increasing proliferation in the adrenal cortex, confirming previous evidence that disulfide bridges are not essential to the N-POMC mitogenic effect. Moreover, cyclin E appears to be involved in the N-POMC- and ACTH-stimulated proliferation in the zona glomerulosa of the adrenal cortex. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Glucocorticoids Exacerbate Lipopolysaccharide-Induced Signaling in the Frontal Cortex and Hippocampus in a Dose-Dependent Manner

Although the anti-inflammatory actions of glucocorticoids (GCs) are well established, evidence has accumulated showing that proinflammatory GC effects can occur in the brain, in a poorly understood manner. Using electrophoretic mobility shift assay, real-time PCR, and immunoblotting, we investigated the ability of varying concentrations of corticosterone (CORT, the GC of rats) to modulate lipopolysaccharide (LPS)-induced activation of NF-kappa B (nuclear factor kappa B), expression of anti- and proinflammatory factors and of the MAP (mitogen-activated protein) kinase family [ERK (extracellular signal-regulated kinase), p38, and JNK/ SAPK (c-Jun N-terminal protein kinase/ stress-activated protein kinase)], and AKT. In the frontal cortex, elevated CORT levels were proinflammatory, exacerbating LPS effects on NF-kappa B, MAP kinases, and proinflammatory gene expression. Milder proinflammatory GCs effects occurred in the hippocampus. In the absence of LPS, elevated CORT levels increased basal activation of ERK1/ 2, p38, SAPK/ JNK, and AKT in both regions. These findings suggest that GCs do not uniformly suppress neuroinflammation and can even enhance it at multiple levels in the pathway linking LPS exposure to inflammation.

Anabolic-androgenic steroid treatment induces behavioral disinhibition and downregulation of serotonin receptor messenger RNA in the prefrontal cortex and amygdala of male mice

Nandrolone is an anabolic-androgenic steroid (AAS) that is highly abused by individuals seeking enhanced physical strength or body appearance. Supraphysiological doses of this synthetic testosterone derivative have been associated with many physical and psychiatric adverse effects, particularly episodes of impulsiveness and overt aggressive behavior. As the neural mechanisms underlying AAS-induced behavioral disinhibition are unknown, we investigated the status of serotonergic system-related transcripts in several brain areas of mice receiving prolonged nandrolone administration. Male C57BL/6J mice received 15 mg/kg of nandrolone decanoate subcutaneously once daily for 28 days, and different sets of animals were used to investigate motor-related and emotion-related behaviors or 5-HT-related messenger RNA (mRNA) levels by real-time quantitative polymerase chain reaction. AAS-injected mice had increased body weight, were more active and displayed anxious-like behaviors in novel environments. They exhibited reduced immobility in the forced swim test, a higher probability of being aggressive and more readily attacked opponents. AAS treatment substantially reduced mRNA levels of most investigated postsynaptic 5-HT receptors in the amygdala and prefrontal cortex. Interestingly, the 5-HT(1B) mRNA level was further reduced in the hippocampus and hypothalamus. There was no alteration of 5-HT system transcript levels in the midbrain. In conclusion, high doses of AAS nandrolone in male mice recapitulate the behavioral disinhibition observed in abusers. Furthermore, these high doses downregulate 5-HT receptor mRNA levels in the amygdala and prefrontal cortex. Our combined findings suggest these areas as critical sites for AAS-induced effects and a possible role for the 5-HT(1B) receptor in the observed behavioral disinhibition.