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1.
Cereb Cortex ; 34(6)2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38863113

RESUMEN

Neuropsychological and neuroimaging studies provide evidence for a degree of category-related organization of conceptual knowledge in the brain. Some of this evidence indicates that body part concepts are distinctly represented from other categories; yet, the neural correlates and mechanisms underlying these dissociations are unclear. We expand on the limited prior data by measuring functional magnetic resonance imaging responses induced by body part words and performing a series of analyses investigating the cortical representation of this semantic category. Across voxel-level contrasts, pattern classification, representational similarity analysis, and vertex-wise encoding analyses, we find converging evidence that the posterior middle temporal gyrus, the supramarginal gyrus, and the ventral premotor cortex in the left hemisphere play important roles in the preferential representation of this category compared to other concrete objects.


Asunto(s)
Mapeo Encefálico , Imagen por Resonancia Magnética , Humanos , Femenino , Masculino , Mapeo Encefálico/métodos , Adulto , Adulto Joven , Formación de Concepto/fisiología , Encéfalo/fisiología , Encéfalo/diagnóstico por imagen , Semántica
2.
Proc Natl Acad Sci U S A ; 119(6)2022 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35115397

RESUMEN

The nature of the representational code underlying conceptual knowledge remains a major unsolved problem in cognitive neuroscience. We assessed the extent to which different representational systems contribute to the instantiation of lexical concepts in high-level, heteromodal cortical areas previously associated with semantic cognition. We found that lexical semantic information can be reliably decoded from a wide range of heteromodal cortical areas in the frontal, parietal, and temporal cortex. In most of these areas, we found a striking advantage for experience-based representational structures (i.e., encoding information about sensory-motor, affective, and other features of phenomenal experience), with little evidence for independent taxonomic or distributional organization. These results were found independently for object and event concepts. Our findings indicate that concept representations in the heteromodal cortex are based, at least in part, on experiential information. They also reveal that, in most heteromodal areas, event concepts have more heterogeneous representations (i.e., they are more easily decodable) than object concepts and that other areas beyond the traditional "semantic hubs" contribute to semantic cognition, particularly the posterior cingulate gyrus and the precuneus.


Asunto(s)
Formación de Concepto/fisiología , Lóbulo Temporal/fisiología , Adulto , Mapeo Encefálico/métodos , Cognición/fisiología , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Lóbulo Parietal/fisiología , Semántica , Adulto Joven
3.
Epilepsia ; 61(9): 1939-1948, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32780878

RESUMEN

OBJECTIVE: To define left temporal lobe regions where surgical resection produces a persistent postoperative decline in naming visual objects. METHODS: Pre- and postoperative brain magnetic resonance imaging data and picture naming (Boston Naming Test) scores were obtained prospectively from 59 people with drug-resistant left temporal lobe epilepsy. All patients had left hemisphere language dominance at baseline and underwent surgical resection or ablation in the left temporal lobe. Postoperative naming assessment occurred approximately 7 months after surgery. Surgical lesions were mapped to a standard template, and the relationship between presence or absence of a lesion and the degree of naming decline was tested at each template voxel while controlling for effects of overall lesion size. RESULTS: Patients declined by an average of 15% in their naming score, with wide variation across individuals. Decline was significantly related to damage in a cluster of voxels in the ventral temporal lobe, located mainly in the fusiform gyrus approximately 4-6 cm posterior to the temporal tip. Extent of damage to this region explained roughly 50% of the variance in outcome. Picture naming decline was not related to hippocampal or temporal pole damage. SIGNIFICANCE: The results provide the first statistical map relating lesion location in left temporal lobe epilepsy surgery to picture naming decline, and they support previous observations of transient naming deficits from electrical stimulation in the basal temporal cortex. The critical lesion is relatively posterior and could be avoided in many patients undergoing left temporal lobe surgery for intractable epilepsy.


Asunto(s)
Anomia/fisiopatología , Lobectomía Temporal Anterior/métodos , Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/cirugía , Hipocampo/cirugía , Complicaciones Posoperatorias/fisiopatología , Lóbulo Temporal/cirugía , Adulto , Anomia/etiología , Lobectomía Temporal Anterior/efectos adversos , Mapeo Encefálico , Femenino , Neuroimagen Funcional , Hipocampo/diagnóstico por imagen , Hipocampo/fisiología , Humanos , Pruebas del Lenguaje , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/fisiología , Adulto Joven
4.
Hippocampus ; 28(5): 358-372, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29473979

RESUMEN

Type 2 diabetes mellitus (T2DM) is an important risk factor for Alzheimer's disease (AD). Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been identified to be effective in T2DM treatment and neuroprotection. In this study, we further explored the effects of a novel unimolecular GLP-1/GIP/Gcg triagonist on the cognitive behavior and cerebral pathology in the 7-month-old triple transgenic mouse model of AD (3xTg-AD), and investigated its possible electrophysiological and molecular mechanisms. After chronic administration of the GLP-1/GIP/Gcg triagonist (10 nmol/kg bodyweight, once daily, i.p.) for 30 days, open field, Y maze and Morris water maze tests were performed, followed by in vivo electrophysiological recording, immunofluorescence and Western blotting experiments. We found that the chronic treatment with the triagonist could improve long-term spatial memory of 3xTg-AD mice in Morris water maze, as well as the working memory in Y maze task. The triagonist also alleviated the suppression of long-term potentiation (LTP) in the CA1 region of hippocampus. In addition, the triagonist significantly reduced hippocampal pathological damages, including amyloid-ß (Aß) and phosphorylated tau aggregates, and upregulated the expression levels of S133 p-CREB, T286 p-CAMKII and S9 p-GSK3ß in the hippocampus of the 3xTg-AD mice. These results demonstrate for the first time that the novel GLP-1/GIP/Gcg triagonist is efficacious in ameliorating cognitive deficits and pathological damages of 3xTg-AD mice, suggesting that the triagonist might be potentially beneficial in the treatment of AD.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Trastornos del Conocimiento/tratamiento farmacológico , Péptido 1 Similar al Glucagón/agonistas , Fármacos Neuroprotectores/farmacología , Receptores de la Hormona Gastrointestinal/agonistas , Receptores de Glucagón/agonistas , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/psicología , Animales , Glucemia/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Modelos Animales de Enfermedad , Femenino , Expresión Génica/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/patología , Potenciación a Largo Plazo/efectos de los fármacos , Masculino , Memoria/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones Transgénicos , Nootrópicos/farmacología
5.
Horm Behav ; 83: 83-92, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27222435

RESUMEN

Alzheimer's disease (AD) is an age-related mental disorder characterized by progressive loss of memory and multiple cognitive impairments. The overproduction and aggregation of Amyloid ß protein (Aß) in the brain, especially in the hippocampus, are closely involved in the memory loss in the patients with AD. Accumulating evidence indicates that the Aß-induced imbalance of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) in the brain plays an important role in the AD pathogenesis and progression. The level of DHEA is elevated, while DHEAS is dramatically decreased in the AD brain. The present study tried to restore the balance between DHEA and DHEAS by using a non-steroidal sulfatase inhibitor DU-14, which increases endogenous DHEAS through preventing DHEAS converted back into DHEA. We found that: (1) DU-14 effectively attenuated the Aß1-42-induced cognitive deficits in spatial learning and memory of rats in Morris water maze test; (2) DU-14 prevented Aß1-42-induced decrease in the cholinergic theta rhythm of hippocampal local field potential (LFP) in the CA1 region; (3) DU-14 protected hippocampal synaptic plasticity against Aß1-42-induced suppression of long term potentiation (LTP). These results provide evidence for the neuroprotective action of DU-14 against neurotoxic Aß, suggesting that up-regulation of endogenous DHEAS by DU-14 could be beneficial to the alleviation of Aß-induced impairments in spatial memory and synaptic plasticity.


Asunto(s)
Péptidos beta-Amiloides/toxicidad , Plasticidad Neuronal/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Memoria Espacial/efectos de los fármacos , Esteril-Sulfatasa/antagonistas & inhibidores , Tiramina/análogos & derivados , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Animales , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/prevención & control , Hipocampo/efectos de los fármacos , Potenciación a Largo Plazo/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/prevención & control , Ratas , Ratas Sprague-Dawley , Tiramina/farmacología , Regulación hacia Arriba/efectos de los fármacos
6.
Sheng Li Xue Bao ; 68(3): 265-75, 2016 Jun 25.
Artículo en Zh | MEDLINE | ID: mdl-27350199

RESUMEN

The accumulation and neurotoxicity of amyloid ß protein (Aß) in the brain is one of major pathological hallmarks of Alzheimer's disease (AD). The effective drugs against Aß have been still deficient up to now. According to a most recent study, (D-Ser2) Oxm, a new antidiabetic drug, not only improves the disorders in plasma glucose and insulin in type 2 diabetes mellitus (T2DM) rats, but also exerts positive effects on hippocampal neurogenesis and synaptogenesis. However, it is still unclear whether (D-Ser2)Oxm can directly protect cultured neurons against Aß1-42-induced cytotoxicity. In the present study, we investigated the neuroprotective effects of (D-Ser2)Oxm on the cultured primary hippocampal neurons by testing the cell viability, neuronal apoptosis, mitochondrial membrane potential and intracellular calcium concentration. The results showed that treatment with (D-Ser2)Oxm effectively reversed Aß1-42-induced decline in cell viability (P < 0.001), and this protective effect could be inhibited by the pretreatment with exendin(9-39), a GLP-1 receptor blocker. (D-Ser2)Oxm treatment also decreased Aß1-42-induced neuronal early apoptosis and down-regulated apoptotic protein caspase3. Meantime, (D-Ser2)Oxm treatment inhibited Aß1-42-induced [Ca(2+)]i elevation, mitochondrial membrane potential depolarization, and glycogen synthase kinase-3ß (GSK3ß) activation. These results suggest that (D-Ser2)Oxm can protect hippocampal neurons against Aß1-42-induced cytotoxicity and this effect may be related to activation of GLP-1 receptors, regulation of intracellular calcium homeostasis and stabilization of mitochondrial membrane potential.


Asunto(s)
Diabetes Mellitus Tipo 2 , Péptidos beta-Amiloides , Animales , Calcio , Supervivencia Celular , Receptor del Péptido 1 Similar al Glucagón , Hipocampo , Hipoglucemiantes , Insulina , Potencial de la Membrana Mitocondrial , Neurogénesis , Neuronas , Fármacos Neuroprotectores , Ratas
7.
Hippocampus ; 25(3): 363-72, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25332198

RESUMEN

Amyloid ß peptide (Aß) has been thought to be neurotoxic and responsible for the impairment of learning and memory in Alzheimer's disease (AD). Humanin (HN), a 24 amino acid polypeptide first identified from the unaffected occipital lobe of an AD patient, is believed to be neuroprotective against the AD-related neurotoxicity. In this study, we investigated the neuroprotective effects of Colivelin (CLN), a novel HN derivative, against Aß by using behavioral test, in vivo electrophysiological recording, and intracellular calcium imaging. Our results showed that intrahippocampal injection of CLN (0.2 nmol) effectively prevented Aß25-35 (4 nmol)-induced deficits in spatial learning and memory of rats in Morris water maze test; the suppression of in vivo hippocampal long term potentiation (LTP) by Aß25-35 was nearly completely prevented by CLN; in addition, CLN pretreatment also effectively inhibited Aß25-35-induced calcium overload in primary cultured hippocampal neurons. These results indicate that CLN has significant neuroprotective properties against Aß, and CLN may holds great promise for the treatment and prevention of AD.


Asunto(s)
Calcio/metabolismo , Homeostasis/efectos de los fármacos , Péptidos y Proteínas de Señalización Intracelular/uso terapéutico , Trastornos de la Memoria/tratamiento farmacológico , Plasticidad Neuronal/efectos de los fármacos , Péptidos beta-Amiloides/toxicidad , Animales , Células Cultivadas , Hipocampo/citología , Potenciación a Largo Plazo/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/inducido químicamente , Neuronas/efectos de los fármacos , Fragmentos de Péptidos/toxicidad , Ratas , Ratas Sprague-Dawley
8.
Horm Behav ; 73: 125-30, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-26135065

RESUMEN

ß-Amyloid (Aß) is the main component of amyloid plaques developed in the brain of patients with Alzheimer's disease (AD). The increasing burden of Aß in the cortex and hippocampus is closely correlated with memory loss and cognition deficits in AD. Recently, leptin, a 16kD peptide derived mainly from white adipocyte tissue, has been appreciated for its neuroprotective function, although less is known about the effects of leptin on spatial memory and synaptic plasticity. The present study investigated the neuroprotective effects of leptin against Aß-induced deficits in spatial memory and in vivo hippocampal late-phase long-term potentiation (L-LTP) in rats. Y maze spontaneous alternation was used to assess short term working memory, and the Morris water maze task was used to assess long term reference memory. Hippocampal field potential recordings were performed to observe changes in L-LTP. We found that chronically intracerebroventricular injection of leptin (1µg) effectively alleviated Aß1-42 (20µg)-induced spatial memory impairments of Y maze spontaneous alternation and Morris water maze. In addition, chronic administration of leptin also reversed Aß1-42-induced suppression of in vivo hippocampal L-LTP in rats. Together, these results suggest that chronic leptin treatments reversed Aß-induced deficits in learning and memory and the maintenance of L-LTP.


Asunto(s)
Péptidos beta-Amiloides/antagonistas & inhibidores , Hipocampo/efectos de los fármacos , Leptina/farmacología , Potenciación a Largo Plazo/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Memoria Espacial/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Animales , Hipocampo/fisiología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/fisiopatología , Trastornos de la Memoria/prevención & control , Memoria a Corto Plazo/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Ratas , Ratas Sprague-Dawley
9.
bioRxiv ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39005307

RESUMEN

Much is known regarding the major white matter pathways connecting the right and left temporal lobes, which project through the posterior corpus callosum, the anterior commissure, and the dorsal hippocampal commissure. However, details about the spatial location of these tracts are unclear, including their exact course and proximity to cortical and subcortical structures, the spatial relations between corpus callosum and anterior commissure projections, and the caudal extent of transcallosal connections within the splenium. We present an atlas of these tracts derived from high angular resolution diffusion tractography maps, providing improved visualization of the spatial relationships of these tracts. The data show several new details, including branching of the transcallosal pathway into medial and lateral divisions, projections of the transcallosal pathway into the external capsule and claustrum, complex patterns of overlap and interdigitation of the transcallosal and anterior commissure tracts, distinct dorsal and ventral regions of the splenium with high tract densities, and absence of temporal lobe projections in the caudal third of the splenium. Intersection of individual tract probability maps with individual cortical surfaces were used to identify likely regions with relatively higher cortical termination densities. These data should be useful for planning surgical approaches involving the temporal lobe and for developing functional-anatomical models of processes that depend on interhemispheric temporal lobe integration, including speech perception, semantic memory, and social cognition. Highlights: Interhemispheric connections of the human temporal lobes were visualized using high angular resolution diffusion tensor imaging tractography.Results are displayed on serial orthogonal sections to reveal detailed spatial relationships.Corpus callosum projections through the splenium form distinct dorsal and ventral bundles and are absent from the caudal splenium.The transcallosal pathway consists of distinct medial and lateral divisions.The results reveal projections to the external capsule and claustrum not previously described.Transcallosal and anterior commissural pathways show complex patterns of overlap and interdigitation.Surface mapping revealed areas with relatively high density of projections to the cortical surface.

10.
Artículo en Zh | MEDLINE | ID: mdl-27255034

RESUMEN

OBJECTIVE: The present study investigated the effects of rapamycin on Aß1-42-induced deficits in working memory and synaptic plasticity. METHODS: After bilateral hippocampal injection of Aß1-42 and rapamycinin rats, spontaneous alternation in Y-maze and in vivo hippocampal long-term potentiation (LTP) of rats were recorded. All data were analized by two-way repeated measures analysis of variance (ANOVA). RESULTS: (Hippocampal injection of Aß1-42 alone impaired working memory of rats; (2) Rapamycin did not affect working memory of rats, but alleviated Aß1-42-induced working memory deficits, compared with Aß1-42 alone group; (Aß1-42 remarkably suppressed in vivo hippocampal LTP of fEPSPs in the CA1 region; (4) Pretreatment with rapamycin prevented Aß1-42-induced suppression of LTP. CONCLUSION: These data indicates that rapamycin could protect against Aß1-42-induced impairments in working memory and synaptic plasticity in rats.


Asunto(s)
Péptidos beta-Amiloides/efectos adversos , Hipocampo/efectos de los fármacos , Memoria a Corto Plazo/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Fragmentos de Péptidos/efectos adversos , Sirolimus/farmacología , Animales , Potenciación a Largo Plazo , Aprendizaje por Laberinto , Ratas
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