RESUMEN
BACKGROUND: Screening for Alzheimer's disease and related disorders (ADRD) and mild cognitive impairment (MCI) could increase case identification, enhance clinical trial enrollment, and enable early intervention. MCI and ADRD screening would be most beneficial if detection measures reflect neurodegenerative changes. Optical coherence tomography (OCT) could be a marker of neurodegeneration (part of the amyloid-tau-neurodegeneration (ATN) framework). OBJECTIVE: To determine whether OCT measurements can be used as a screening measure to detect individuals with MCI and ADRD. METHODS: A retrospective cross-sectional study was performed on 136 participants with comprehensive clinical, cognitive, functional, and behavioral evaluations including OCT with a subset (nâ=â76) completing volumetric MRI. Pearson correlation coefficients tested strength of association between OCT and outcome measures. Receiver operator characteristic curves assessed the ability of OCT, patient-reported outcomes, and cognitive performance measures to discriminate between individuals with and without cognitive impairment. RESULTS: After controlling for age, of the 6 OCT measurements collected, granular cell layer-inner plexiform layer (GCLâ+âIPL) thickness best correlated with memory, global cognitive performance, Clinical Dementia Rating, and hippocampal atrophy. GCLâ+âIPL thickness provided good discrimination in cognitive status with a cut-off score of 75µm. Combining GCLâ+âIPL thickness as a proxy marker for hippocampal atrophy with a brief patient-reported outcome and performance measure correctly classified 87%of MCI and ADRD participants. CONCLUSION: Multimodal approaches may improve recognition of MCI and ADRD. OCT has the potential to be a practical, non-invasive biomarker for ADRD providing a screening platform to quickly identify at-risk individuals for further clinical evaluation or research enrollment.
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Disfunción Cognitiva/diagnóstico , Demencia/diagnóstico , Tamizaje Masivo , Evaluación de Resultado en la Atención de Salud , Tomografía de Coherencia Óptica , Anciano , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas/estadística & datos numéricos , Estudios RetrospectivosRESUMEN
Toll-like receptors (TLRs) participate in the response to infection, stress, and injury by initiating an innate immune response. In addition, these receptors are expressed in many neural cell types and under physiological conditions are implicated in modulating cognitive function and neural plasticity in the adult and aged brain. Knockout of the Toll-like receptor 4 (TLR4) subtype enhances spatial memory and adult hippocampal neurogenesis through increasing proliferation and neuronal differentiation. Currently unknown is whether pharmacological inhibition of TLR4 produces similar enhancements in cognitive function and cell proliferation. The present study evaluated water maze performance, cytokine expression, and cell proliferation in the hippocampus of young and aged male and female C57BL6/J mice following treatment with the TLR4 antagonist, TAK-242. Further, alterations in the response to an acute stressor were evaluated in TAK-242-treated mice. Results showed that TAK-242 selectively enhanced spatial learning and memory in young females. Additionally, TAK-242 treatment reduced thigmotaxis in the water maze and lowered corticosterone levels following acute stress in females. TAK-242 decreased hippocampal interleukin (IL)-1ß expression but had no effect on IL-6 or tumor necrosis factor-α (TNFα). Aged mice showed decreased cell proliferation compared to young mice, but TAK-242 administration had minimal effects on estimated Ki67 positive cell numbers. Findings indicate that pharmacological inhibition of TLR4 improves cognitive function in young females likely through attenuating stress reactivity.
Asunto(s)
Memoria Espacial , Receptor Toll-Like 4 , Animales , Proliferación Celular , Femenino , Hipocampo/metabolismo , Masculino , Ratones , Ratones Noqueados , Receptor Toll-Like 4/metabolismoRESUMEN
The onset of puberty is associated with the psychophysiological maturation of the adolescent to an adult capable of reproduction when olfactory signals play an important role. This period begins with the secretion of the gonadotropin-releasing hormone (GnRH) from GnRH neurons within the hypothalamus. This is regulated by kisspeptin neurons that express high levels of transmembrane prolactin receptors (PRLR) that bind to and are activated by prolactin (PRL). The elevated levels of serum PRL found during lactation, or caused by chronic PRL infusion, decreases the secretion of gonadotropins and kisspeptin and compromised the estrous cyclicity and the ovulation. In the present work, we aimed to evaluate the effects of either increased or decreased PRL circulating levels within the peripubertal murine brain by administration of PRL or treatment with cabergoline (Cab) respectively. We showed that either treatment delayed the onset of puberty in females, but not in males. This was associated with the augmentation of the PRL receptor (Prlr) mRNA expression in the arcuate nucleus and decreased Kiss1 expression in the anteroventral periventricular zone. Then, during adulthood, we assessed the activation of the mitral and granular cells of the main (MOB) and accessory olfactory bulb (AOB) by cFos immunoreactivity (ir) after the exposure to soiled bedding of the opposite sex. In the MOB, the PRL treatment promoted an increased cFos-ir of the mitral cells of males and females. In the granular cells of male of either treatment an augmented activation was observed. In the AOB, an impaired cFos-ir was observed in PRL and Cab treated females after exposure to male soiled bedding. However, in males, only Cab impaired its activation. No effects were observed in the AOB-mitral cells. In conclusion, our results demonstrate that PRL contributes to pubertal development and maturation of the MOB-AOB during the murine juvenile period in a sex-dependent way.
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Maduración Sexual , Animales , Núcleo Arqueado del Hipotálamo/metabolismo , Femenino , Hormona Liberadora de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Kisspeptinas/genética , Kisspeptinas/metabolismo , Masculino , Ratones , Corteza Olfatoria , Prolactina , PubertadRESUMEN
Hippocampus is one of the brain regions in which neuroplastic changes occur. Paradigms such as environmental enrichment (ENR) have been used to prevent or delay the neuroplastic changes of the hippocampus during aging. Here, we investigated the beneficial effects of ENR on dendritic spines and hippocampal neurogenesis in middle age Balb/c mice. ENR increased the number of dendritic spines, cell survival, and intermediate stages of the hippocampal neurodevelopment process. Also, ENR alters the distribution of cells involved in the neurogenic process along the dorsal-ventral dentate gyrus. In addition, ENR increased the proportion of cells with more mature dendritic morphology and net hippocampal neurogenesis. Whole-hippocampus protein extracts revealed that ENR increases the levels of BDNF, phospho-Akt and phospho-MAPK1/2, suggesting that the positive effects of ENR on neuroplasticity in middle age Balb/c mice involve the participation of these key-signaling proteins. Our results suggest that ENR is a relevant strategy to prevent neuroplastic decline by increasing the formation of both dendritic spines and new neurons in the hippocampus during middle age.
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Espinas Dendríticas/ultraestructura , Ambiente , Hipocampo/metabolismo , Hipocampo/ultraestructura , Neurogénesis/fisiología , Plasticidad Neuronal , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteína Doblecortina , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Ratones , Ratones Endogámicos BALB C , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Garlic and garlic extracts are used as seasonings and are generally considered beneficial to human health, which include antioxidant and neuroprotective properties in neurological disorders. In the present study, we examined the effects of garlic sulfur components on the proliferation of neural progenitor cells (NPCs) and hippocampal neurogenesis. Of the sulfur compounds extracted, diallyl disulfide (DADS) significantly suppressed the proliferation of NPCs, whereas other sulfur containing components had no effect. In order to investigate the effect of DADS on adult hippocampal neurogenesis, DADS was administered orally to young (6 week-old) male C57BL/6 mice for 2 weeks. It was found that 10 mg/kg of DADS significantly decreased the proliferation of NPCs in the dentate gyrus without affecting the survival of newly generated cells. Furthermore, DADS decreased levels of hippocampal BDNF, phosphorylated CREB signaling, and phosphorylated ERKs, which are known to be related to hippocampal neurogenesis and NPCs proliferation. In addition, DADS induced significant memory defects as compared with controls. We report that DADS may have adverse effects on hippocampal neurogenesis and neurocognitive functions by modulating ERK and BDNF-CREB signaling, and suggest that the advisability of consuming large amounts of garlic products should be considered, particularly during the period of neural growth.
Asunto(s)
Compuestos Alílicos/toxicidad , Giro Dentado/efectos de los fármacos , Disulfuros/toxicidad , Células-Madre Neurales/efectos de los fármacos , Neurogénesis/efectos de los fármacos , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteína de Unión a CREB/metabolismo , Proliferación Celular/efectos de los fármacos , Cognición/efectos de los fármacos , Giro Dentado/metabolismo , Giro Dentado/patología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Ajo/química , Masculino , Memoria/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Ratones , Ratones Endogámicos C57BL , Células-Madre Neurales/metabolismo , Células-Madre Neurales/patología , Fosforilación , Extractos Vegetales/toxicidad , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Hormones influence various normal biological processes in the skin and hairs. OBJECTIVE: This study was undertaken to investigate the presence of estrogen receptors(ER) and progesterone receptors (PR) in the skin and to assess differences in sex and age. METHODS: We examined seven normal volunteers' skin. The mouse monoclonal antibodies against human ER and PR were used to identify the localization of ER and PR in the frozen tissue sections by using a standard two stage indirect immunoperoxidase technique. RESULTS: The granular layer of epidermis and infundibulum of hair follicle in all the samples showed strong positivity of PR. Although each skin section did not contain all skin appendages, most of the samples showed that eccrine gland duct, inner root sheath of hair follicle stained weakly positive of PR. ER was not demonstrate in all samples epidermis. CONCLUSION: PR was presented in the granular layer of epidermis, infundibulum of hair follicle, eccrine gland duct, and inner root sheath of hair follicle. Therefore, we might suspect that the progesterone probably contributes to the keratinization of the skin because these positively staining sites are prior to complete keratinization layers.