Chronic restraint stress produces sex-specific behavioral and molecular outcomes in the dorsal and ventral rat hippocampus.

Stress-related disorders display differences at multiple levels according to sex. While most studies have been conducted in male rodents, less is known about comparable outcomes in females. In this study, we found that the chronic restraint stress model (2.5 h/day for 14 days) triggers different somatic responses in male and female adult rats. Chronic restraint produced a loss in sucrose preference and novel location preference in male rats. However, chronic restraint failed to produce loss of sucrose preference in females, while it improved spatial performance. We then characterized the molecular responses associated with these behaviors in the hippocampus, comparing the dorsal and ventral poles. Notably, sex- and hippocampal pole-specific transcriptional signatures were observed, along with a significant concordance between the female ventral and male dorsal profiles. Functional enrichment analysis revealed both shared and specific terms associated with each pole and sex. By looking into signaling pathways that were associated with these terms, we found an ample array of sex differences in the dorsal and, to a lesser extent, in the ventral hippocampus. These differences were mainly present in synaptic TrkB signaling, Akt pathway, and glutamatergic receptors. Unexpectedly, the effects of stress on these pathways were rather minimal and mostly dissociated from the sex-specific behavioral outcomes. Our study suggests that female rats are resilient and males susceptible to the restraint stress exposure in the sucrose preference and object location tests, while the activity of canonical signaling pathways is primarily determined by sex rather than stress in the dorsal and ventral hippocampus.

Static compression regulates OPG expression in periodontal ligament cells via the CAMK II pathway

ABSTRACT Objective This study aimed to investigate the potential role of CAMK II pathway in the compression-regulated OPG expression in periodontal ligament cells (PDLCs). Material and Methods The PDL tissue model was developed by 3-D culturing human PDLCs in a thin sheet of poly lactic-co-glycolic acid (PLGA) scaffolds, which was subjected to static compression of 25 g/cm2 for 3, 6 and 12 h, with or without treatment of KN-93. After that, the expression of OPG, RANKL and NFATC2 was investigated through real-time PCR and western blot analysis. Results After static compression, the NFATC2 and RANKL expression was significantly up-regulated, while partially suppressed by KN-93 for 6 and 12 h respectively. The OPG expression was significantly down-regulated by compression in 3 h, started to elevate in 6 h, and significantly up-regulated in 12 h. The up-regulation after 12 h was significantly suppressed by KN-93. Conclusions Long-term static compression increases OPG expression in PDLCs, at least partially, via the CAMK II pathway.

Pedunculopontine Nucleus Gamma Band Activity-Preconscious Awareness, Waking, and REM Sleep.

The pedunculopontine nucleus (PPN) is a major component of the reticular activating system (RAS) that regulates waking and REM sleep, states of high-frequency EEG activity. Recently, we described the presence of high threshold, voltage-dependent N- and P/Q-type calcium channels in RAS nuclei that subserve gamma band oscillations in the mesopontine PPN, intralaminar parafascicular nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD). Cortical gamma band activity participates in sensory perception, problem solving, and memory. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions. That is, the RAS may play an early permissive role in volition. Our latest results suggest that (1) the manifestation of gamma band activity during waking may employ a separate intracellular pathway compared to that during REM sleep, (2) neuronal calcium sensor (NCS-1) protein, which is over expressed in schizophrenia and bipolar disorder, modulates gamma band oscillations in the PPN in a concentration-dependent manner, (3) leptin, which undergoes resistance in obesity resulting in sleep dysregulation, decreases sodium currents in PPN neurons, accounting for its normal attenuation of waking, and (4) following our discovery of electrical coupling in the RAS, we hypothesize that there are cell clusters within the PPN that may act in concert. These results provide novel information on the mechanisms controlling high-frequency activity related to waking and REM sleep by elements of the RAS.

AMP-activated protein kinase (AMPK): the key role in metabolic regulation and control of food intake: [review] / Proteína quinase ativada por AMP (AMPK): o papel-chave na regulação metabólica e controle da ingestão alimentar: [revisão]

Obesity is a clinical condition which has been viewed as a serious and growing public health problem. Excessive body weight has been shown to predispose to several diseases, mainly cardiovascular diseases, type 2 diabetes, and metabolic syndrome. AMP-activated protein kinase (AMPK) plays a potential role in food intake control in the hypothalamus and peripheral tissues. In vivo administration of leptin, which leads to a reduction of food intake, decreases hypothalamic AMPK activity. In peripheral tissues, AMPK regulates a variety of metabolic pathways that result in the suppression of ATP consumption (anabolic pathway) and the induction of ATP production (catabolic pathway). These include stimulating fatty acid uptake and oxidation and glucose uptake in multiple tissues: stimulating mitochondrial biogenesis in the skeletal muscle, stimulating glycolysis in the heart, inhibiting fatty acid synthesis in the liver and adipocyte, inhibiting cholesterol synthesis and glucogenesis in the liver, and inhibiting insulin secretion from pancreatic β-cells. AMPK is activated in response to environmental or nutritional stress factors, including thermal shock, hypoxia, glucose deprivation, calorie restriction, fasting, epigallocatechin-3-gallate consumption, resveratrol, exercising, ethanol consumption, n-3 (PUFA), statins, or troglitazone. These outcomes demonstrate that AMPK plays a key role in the regulation of feeding, indicating AMPK as a new target in the study of the anti-metabolic syndrome. Particularly, this review with recent findings show how AMPK activation coordinates the metabolic regulations and food intake control under different metabolic and nutritional circumstances.

La obesidad es una condición clínica vista como un serio y creciente problema de salud pública. Está demostrado que el exceso de peso corporal es un factor que predispone para muchas enfermedades, particularmente las cardiovasculares, diabetes mellitus y síndrome metabólico. La proteína quinasa AMP-activada (AMPK) en los tejidos periféricos y el hipotálamo tiene un papel importante sobre el control de la ingestión de alimentos. La administración de leptina in vivo conduce a la reducción de la ingestión energética, disminuyendo la actividad hipotalámica de la AMPK. En los tejidos periféricos, la AMPK regula una variedad de vías metabólicas provocando supresión del consumo de ATP (vía anabólica) e inducción de la producción de ATP (vía catabólica). Incluyendo estimulo a la captación de ácidos grasos y oxidación y captación de glucosa en diversos tejidos: estimulación de la glucosa en el corazón, inhibición de la síntesis de ácidos grasos en hígado y en los adipocitos, inhibición de la síntesis de colesterol y de la glicogénesis en el hígado e inhibición de la secreción de insulina por las células beta del páncreas. La AMPK es activada en repuesta a factores de stress ambiental o nutricional, incluyendo: choque térmico, hipoxia, pr ivación de glucosa, restricción calórica, ayuno, epigalocatequina-3-galato, estatinas o troglitazona. Eses datos demuestran la AMPK como nuevo objeto de estudio anti-síndrome metabólico. En especial, esta revisión sobre pesquisas recientes muestra como la activación de la AMPK coordina las regulaciones metabólicas y el control de la ingestión alimentar en diferentes circunstancias metabólicas y nutricionales.

A obesidade é uma condição clínica que é vista como um sério e crescente problema de saúde pública. O excesso de peso corporal tem demonstrado ser fator predisponente para várias doenças, particularmente as doenças cardiovasculares, diabetes tipo 2 e síndrome metabólica. A proteína quinase AMP-ativada (AMPK) nos tecidos periféricos e hipotálamo tem um papel importante no controle do consumo alimentar. A administração de leptina in vivo conduz à redução da ingestão energética, diminuindo a atividade hipotalâmica da AMPK. Nos tecidos periféricos, a AMPK regula uma variedade de rotas metabólicas que resultam na supressão do consumo de ATP (rota anabólica) e na indução da produção de ATP (rota catabólica). Estas rotas incluem estimulação da captação de ácidos graxos e oxidação e captação de glicose em diversos tecidos: estimulação da biogênese mitocondrial no músculo esquelético, estimulação da glicólise no coração, inibição da síntese de ácidos graxos no fígado e nos adipócitos, inibição da síntese de colesterol e da glicogênese no fígado, e inibição da secreção de insulina pelas células β-pancreática. A AMPK é ativada em resposta a fatores de estresse ambiental ou nutricional, incluindo: choque térmico, hipóxia, privação de glicose, restrição calórica, jejum, epigalocatequina-3-galato, resveratrol, exercício físico, consumo de etanol/álcool, n-3 (PUFA), estatinas ou troglitazona. Esses dados demonstram que a AMPK tem um papel chave na regulação da alimentação, indicando a AMPK como um novo alvo no estudo da antissíndrome metabólica. Em especial, esta revisão com recentes pesquisas mostra como a ativação da AMPK coordena as regulações metabólicas e o controle da ingestão alimentar em diferentes circunstâncias metabólicas e nutricionais.