Environmental enrichment: dissociated effects between physical activity and changing environmental complexity on anxiety and neurogenesis in adult male Balb/C mice.

Several factors, including environmental modifications, stimulate neuroplasticity. One type of neuroplasticity consists in the generation of new neurons in the dentate gyrus of the hippocampus. Neurogenesis is modulated by environmental enrichment (ENR, tunnels plus running wheel) and affected by the time of exposure to ENR. Despite the wide use of ENR to stimulate neuroplasticity, the degree to which ENR variations modeled by temporally changing the level of environmental complexity affect hippocampal neurogenesis and anxiety is still unclear. Thus, we investigated the effects of five housing conditions on young adult male Balb/C mice exposed for 42 days. The groups were as follows: standard conditions without ENR, constant ENR complexity, gradual increase of ENR complexity followed by a gradual decrease of ENR complexity, gradual increase of ENR complexity followed by constant ENR complexity, and constant ENR complexity followed by a gradual decrease of ENR complexity. On day 44, mice were exposed to the elevated plus-maze to evaluate anxiety. Further, we analyzed neurogenesis and quantified corticosterone levels. In an additional experiment, we explored the effect of voluntary physical activity on anxiety, neurogenesis, and corticosterone during the variations in ENR complexity. Our results showed that any change in ENR complexity over time reduced anxiety. Also, voluntary physical activity alone or in the context of a complex environment increased doublecortin cell maturation in the granular cell layer of the hippocampus. Finally, our study supports that physical activity acts proneurogenic, whereas any change in environmental complexity decreases anxiety-like behavior. However, the decrease in corticosterone levels elicited by physical activity was lower than the decrease produced by the decrement in environmental complexity.

[Oral squamous cell carcinoma. Case report and review of literature]. / Carcinoma escamocelular bucal. Caso clínico y revisión de la literatura.

Background: Squamous cell cancer (SCC) represents 90-95% of all types of cancer. In Mexico, the frequency of oral SCC (OSCC) has increased, with an incidence between 1 and 5%. OSCC is associated with subjects in the 5th and 7th decade of life, males, positive for smoking, alcoholism, genetic factors, immunosuppression, human papillomavirus (HPV) infection, and unhealthy lifestyles, among others. The objective of this work was to present a clinical case as an example of the emerging characteristics in a patient with OSCC. Clinical case: 38-year-old female patient, with indurated ulcer, partially adhered to deep planes and painful, associated with an increase in volume, located on the belly and lateral edge of the tongue. A biopsy was performed and with the histopathological diagnosis of well differentiated invasive squamous cell carcinoma, the presence of HPV was determined, resulting positive for HPV-16. Combined cancer treatment was performed (surgical-radiation-chemotherapy), with good results for the patient regarding aesthetics and function. Conclusions: We analyzed several studies evaluating the presence of HPV in lesions of OSCC, as a risk factor that involves more frequently cases of young patients, with location in tongue, and negative antecedents for smoking and alcoholism compared to cases of OSCC not associated with HPV. Data are required to help elucidate various still unknown aspects of oral HPV infection and its relationship with OSCC.

Introducción: el cáncer escamocelular (CEC) representa el 90-95% de todos los tipos de cáncer. En México, la frecuencia de CEC bucal (CECB) se ha incrementado y presenta una incidencia entre el 1 y el 5%. El CECB se asocia con sujetos en la quinta y séptima década de la vida, el sexo masculino, positivos a tabaquismo, alcoholismo, factores genéticos, inmunosupresión, infección por virus del papiloma humano (VPH) y estilos de vida poco saludables, entre otros. El objetivo de este trabajo fue presentar un caso clínico como ejemplo de las características emergentes en un paciente con CECB. Caso clínico: mujer de 38 años, con úlcera indurada, parcialmente adherida a planos profundos y dolorosa, asociada con un aumento de volumen, ubicada en vientre y borde lateral de lengua. Se realizó biopsia y con el diagnóstico histopatológico de carcinoma escamocelular invasor bien diferenciado, se procedió a determinar la presencia del VPH y resultó positivo a VPH-16. Se realizó tratamiento oncológico combinado (quirúrgico-radiación-quimioterapia), con buenos resultados para la paciente respecto a la estética y función. Conclusiones: se analizaron varios estudios que evalúan la presencia del VPH en lesiones de CECB, como un factor de riesgo que involucra con mayor frecuencia casos de pacientes jóvenes, la localización en lengua y antecedentes negativos para tabaquismo y alcoholismo frente a casos de CECB no asociados al VPH. Se requieren datos que contribuyan a dilucidar diversos aspectos aún desconocidos sobre la infección bucal por VPH y su relación con el CECB.

Carcinoma escamocelular bucal. Caso clínico y revisión de la literatura / Oral squamous cell carcinoma. Case report and review of literature

Introducción: el cáncer escamocelular (CEC) representa el 90-95% de todos los tipos de cáncer. En México, la frecuencia de CEC bucal (CECB) se ha incrementado y presenta una incidencia entre el 1 y el 5%. El CECB se asocia con sujetos en la quinta y séptima década de la vida, el sexo masculino, positivos a tabaquismo, alcoholismo, factores genéticos, inmunosupresión, infección por virus del papiloma humano (VPH) y estilos de vida poco saludables, entre otros. El objetivo de este trabajo fue presentar un caso clínico como ejemplo de las características emergentes en un paciente con CECB. Caso clínico: mujer de 38 años, con úlcera indurada, parcialmente adherida a planos profundos y dolorosa, asociada con un aumento de volumen, ubicada en vientre y borde lateral de lengua. Se realizó biopsia y con el diagnóstico histopatológico de carcinoma escamocelular invasor bien diferenciado, se procedió a determinar la presencia delVPH y resultó positivo a VPH 16. Se realizó tratamiento oncológico combinado (quirúrgico-radiación-quimioterapia), con buenos resultados para la paciente respecto a la estética y función. Conclusiones: se analizaron varios estudios que evalúan la presencia del VPH en lesiones de CECB, como un factor de riesgo que involucra con mayor frecuencia casos de pacientes jóvenes, la localización en lengua y antecedentes negativospara tabaquismo y alcoholismo frente a casos de CECB no asociados al VPH. Se requieren datos que contribuyan a dilucidar diversos aspectos aún desconocidos sobre la infección bucal por VPH y su relación con el CECB.

Background: Squamous cell cancer (SCC) represents 90-95% of all types of cancer. In Mexico, the frequency of oral SCC (OSCC) has increased, with an incidence between 1 and 5%. OSCC is associated with subjects in the 5 and 7th decade of life, males, positive for smoking, alcoholism, genetic factors, immunosuppression, human papillomavirus (HPV) infection, and unhealthy lifestyles, among others. Theobjectiveof thisworkwas to presenta clinical case as an example of the emerging characteristics in a patient with OSCC. Clinical case: 38-year-old female patient, with indurated ulcer, partially adhered to deep planes and painful, associated with an increase in volume, located on the belly and lateral edge of the tongue. A biopsy was performed and with the histopathological diagnosis of well differentiated invasive squamous cell carcinoma, the presence of HPV was determined, resulting positive for HPV-16. Combined cancer treatment was performed (surgical radiation-chemotherapy), with good results for the patient regarding aesthetics and function. Conclusions: We analyzed several studies evaluating the presence of HPV in lesions of OSCC, as a risk factor that involves more frequently cases of young patients, with location in tongue, and negative antecedents for smoking and alcoholism compared to cases of OSCC not associated with HPV. Data are required to help elucidate various still unknown aspects of oral HPV infection and its relationship with OSCC.

Piper auritum Kunth (Piperaceae) improves the sexual performance of sluggish male rats through enhancing ejaculation.

ETHNOPHARMACOLOGICAL RELEVANCE: Piper auritum Kunth is employed as an aphrodisiac in the traditional medicine, but corroborative evidence for such effect is scarce. AIM OF THE STUDY: The pro-sexual effect of an aqueous extract of P. auritum and its possible mechanisms were analyzed in two paradigms of male sexual function. MATERIAL AND METHODS: Effects of an aqueous extract of P. auritum (PA, single administration) were investigated in the fictive ejaculation, and copulatory behavior paradigms in sexually sluggish male rats. WAY 100635 (antagonist of 5-HT1A receptors), atosiban (antagonist of oxytocinergic receptors), L-NAME (inhibitor of the nitric oxide synthase) and baclofen (antagonist of GABAB receptors) were used as pre-treatments in order to investigate the role of different neurotransmitter systems in PA actions. Chemical profile of PA was determined by Gases Chromatography and Ultra Performance Chromatography-Electrospray Ionization-Masses Spectrometry (UPLC-ESI-MS). RESULTS: In males with retarded ejaculation, PA stimulated ejaculatory behavior and recovered electromyographic activity of pelvic musculature participating in seminal emission and ejaculation. All pre-treatments blocked stimulating effects of PA on the fictive ejaculation; additionally WAY 100635 interfered with PA actions on ejaculatory behavior. Safrol, apigenin dimethylether, myristicin, vaccihein A, sakuranin and sakuranetin flavonoids, were main constituents of PA, with possible participation in its pro-sexual effects. CONCLUSIONS: Pro-sexual effects of P. auritum elicited at level of ejaculation were mediated by several neurotransmitter systems, among which serotonin and its 5-HT1A receptors play an important role. Present findings support P. auritum reputation as an aphrodisiac, with potential use in delayed ejaculation disorder.

Resveratrol Enhances Neuroplastic Changes, Including Hippocampal Neurogenesis, and Memory in Balb/C Mice at Six Months of Age.

Resveratrol (RVTL) is a flavonoid found in red wine and has been publicized heavily as an anti-aging compound. Indeed, basic research confirms that although there is much hype in the promotion of RVTL, flavonoids such as RVTL have a wide range of biological effects. We here investigated the effects of RVTL treatment on hippocampal plasticity and memory performance in female Balb/C mice, a strain with low baseline levels of adult neurogenesis. Two weeks of treatment with RVTL (40 mg/kg) induced the production of new neurons in vivo by increasing cell survival and possibly precursor cell proliferation. In addition, RVTL decreased the number of apoptotic cells. The number of doublecortin (DCX)-expressing intermediate cells was increased. RVTL stimulated neuronal differentiation in vitro without effects on proliferation. In the dentate gyrus, RVTL promoted the formation and maturation of spines on granule cell dendrites. RVTL also improved performance in the step down passive avoidance test. The RVTL-treated mice showed increase in the levels of two key signaling proteins, phospho-Akt and phospho-PKC, suggesting the involvement of these signaling pathways. Our results support the vision that flavonoids such as resveratrol deserve further examination as plasticity-inducing compounds in the context of successful cognitive aging.

Participation of GABAA, GABA(B) receptors and neurosteroids in toluene-induced hypothermia: evidence of concentration-dependent differences in the mechanism of action.

Toluene is a misused substance that modifies γ-aminobutyric acid (GABA) release and shares behavioral and molecular effects with GABA(A) and GABA(B) receptor agonists. GABAergic compounds are involved in thermoregulation processes and volatile substance users have reported that one of the reasons to inhale is to avoid feeling cold. At present, no studies have analyzed the effects of inhalants on body temperature and the mechanism of action involved. Thus, the main purpose of this study was to evaluate the effects of a (60 min) acute toluene inhalation (2000, 4000 and 6000 ppm) in core temperature. In addition, we tried to prevent the changes of temperature induced by toluene with the specific GABA(A) receptor blockers picrotoxin (0.01-0.1mg/kg), bicuculline (0.1-0.3mg/kg), and flumazenil (3-30 mg/kg); the GABA(B) receptor antagonist phaclofen (10-30 mg/kg) and the neurosteroid synthesis inhibitor finasteride (10-30 mg/kg). Results show that toluene reduced core temperature in mice in a concentration-dependent manner. The hypothermia produced by 4000 ppm toluene was prevented by picrotoxin, bicuculline, phaclofen and finasteride but not by flumazenil. In contrast none of these antagonists tested blocked the effects of 6000 ppm toluene. In conclusion, toluene decreases core temperature, GABA receptors and neurosteroids participate in toluene's action at 4000 ppm; but other mechanisms of action are involved in the hypothermic effects of 6000 ppm toluene.

Regulación de la neurogénesis hipocámpica por los estrógenos: su relación con la depresión / Regulation of adult hippocampal neurogenesis by estrogens: relationship to depression

Estrogens produce a wide range of biological effects throughout the body, including the Central Nervous System (CNS). In the brain, besides acting as neuroprotective agents, estrogens play an important role in many neuronal processes and certain psychiatric disorders such as depression. The precise mechanism by which estrogens induce their positive effects on depressive disorders has not been elucidated; however, it is known that estrogens act on the CNS through the activation of specific receptors. These actions occur in genomic and non-genomics mechanisms through the modulation of synthesis and metabolism of neurotransmitters, neuropeptides, neurosteroids and influencing the morphological features of neurons and synaptic function. In addition, it is known that estrogens can act as modulators of processes related to neuroplasticity and neurogenesis. Adult hippocampal neurogenesis is a neuroplastic process that is affected by antidepressant drugs. These drugs increase the number of new neurons following a temporal course that correlates within the time in which antidepressants cause a behavioral improvement in rodents and in humans. Interestingly, whereas the behavioral antidepressant effects require 2-4 weeks to appear, after treatment initiation, estrogen reduce the depressive-like behavior and induce cell proliferation in terms of days. Thus, antidepressant drugs and the estrogens replacement during the adulthood could influence in a similar manner the new neuron formation. Furthermore, recent works have indicated that the combination of antidepressants plus estrogens could exert beneficial actions at lower doses of estrogens (physiological range). This evidence is important due to the combination of non-effective doses of antidepressants plus estrogens could decrease the side-effects of both compounds, and facilitate the behavioral action of antidepressant drugs shortening the latency to onset their action. The present review discusses recent information about the implication of estrogens in depression, and on their effects as positive regulators of new neuron formation in the adult hippocampus. In addition, we will review the possible implication of last effect of estrogens on their antidepressant effects.

Los estrógenos producen una amplia gama de efectos biológicos en todo el cuerpo, incluyendo el Sistema Nervioso Central (SNC). En el cerebro, además de actuar como agentes neuroprotectores, los estrógenos desempeñan un papel importante en la regulación de procesos neuronales constituyéndose así como posibles factores relacionados con la etiología de algunos trastornos neuropsiquiátricos, tales como la depresión. Durante los últimos años se ha generado evidencia de la relación existente entre los niveles fisiológicos de los estrógenos y el desarrollo de episodios depresivos. Por otra parte, los estrógenos tienen un papel importante en la inducción de cambios a nivel de la plasticidad neuronal y de la neurogénesis en el hipocampo adulto. A este respecto se ha observado que los estrógenos regulan el desarrollo, la maduración y la sobrevivencia de las nuevas neuronas en el cerebro adulto, de la misma manera que lo hacen los tratamientos antidepresivos. Los efectos de los estrógenos sobre la neurogénesis y la plasticidad neuronal podrían estar regulados por los receptores a estrógenos, tanto el receptor alfa (REα), como el receptor beta (REβ). Ambos subtipos de receptores se expresan en el hipocampo del cerebro adulto. Así mismo, el hipocampo es una estructura que participa en procesos cognitivos y de memoria y existe evidencia que muestra su participación en la etiología de la depresión y sobre el efecto de los fármacos antidepresivos. La neurogénesis ha sido considerada como un proceso dinámico por medio del cual se forman neuronas funcionales. De tal modo que este proceso también involucra los eventos de sobrevivencia, maduración dendrítica y axonal, así como el establecimiento de conexiones sinápticas para la integración final de las nuevas neuronas en los circuitos neuronales existentes, eventos que son modulados por los fármacos antidepresivos. En el presente artículo se revisa información reciente acerca de los efectos de los estrógenos sobre la depresión y sobre su relación con la neurogénesis hipocámpica.

Melatonin supplementation delays the decline of adult hippocampal neurogenesis during normal aging of mice.

Melatonin modulates adult hippocampal neurogenesis in adult mice. Also, plasma melatonin levels and new neuron formation decline during aging probably causing cognitive alterations. In this study, we analyzed the impact of exogenous supplementation with melatonin in three key events of hippocampal neurogenesis during normal aging of mice. The analysis was performed in rodents treated with melatonin during 3, 6, 9 or 12 months. We found an increase in cell proliferation in the dentate gyrus of the hippocampus after 3, 6 and 9 months of treatment (>90%). Additionally, exogenous melatonin promoted survival of new cells in the dentate gyrus (>50%). Moreover, melatonin increased the number of doublecortin-labeled cells after 6 and 9 months of treatment (>150%). In contrast, melatonin administered during 12 months did not induce changes in hippocampal neurogenesis. Our results indicate that melatonin also modulates the neurogenic process in the hippocampus during normal aging of mice. Together, the data support melatonin as one of the positive endogenous regulators of neurogenesis during aging.