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1.
Cell ; 186(17): 3726-3743.e24, 2023 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-37442136

RESUMEN

Elucidating the cellular organization of the cerebral cortex is critical for understanding brain structure and function. Using large-scale single-nucleus RNA sequencing and spatial transcriptomic analysis of 143 macaque cortical regions, we obtained a comprehensive atlas of 264 transcriptome-defined cortical cell types and mapped their spatial distribution across the entire cortex. We characterized the cortical layer and region preferences of glutamatergic, GABAergic, and non-neuronal cell types, as well as regional differences in cell-type composition and neighborhood complexity. Notably, we discovered a relationship between the regional distribution of various cell types and the region's hierarchical level in the visual and somatosensory systems. Cross-species comparison of transcriptomic data from human, macaque, and mouse cortices further revealed primate-specific cell types that are enriched in layer 4, with their marker genes expressed in a region-dependent manner. Our data provide a cellular and molecular basis for understanding the evolution, development, aging, and pathogenesis of the primate brain.


Asunto(s)
Corteza Cerebral , Macaca , Análisis de la Célula Individual , Transcriptoma , Animales , Humanos , Ratones , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Macaca/metabolismo , Transcriptoma/genética
2.
Neurochem Int ; 138: 104774, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32474176

RESUMEN

Olfactory dysfunction is related with various neurodegenerative and neuropsychiatric disorders such as Alzheimer's disease and Parkinson's disease, which show impaired cognitive functions. However, the effects of olfactory dysfunction on hippocampal dependent learning and memory remain elusive. In this study, mice were treated with intranasal zinc sulfate (ZnSO4) infusion which resulted in a complete but reversible loss of olfactory function. Olfaction was totally destroyed even 1 week after zinc sulfate treatment, but partially recovered 4 weeks later. We found learning and memory in Y-maze and fear conditioning were not affected by ZnSO4 1 week after the treatment, but learning and memory were severely destroyed 4 weeks later. Electrophysiology results showed impaired hippocampal long-term potentiation and long-term depression 4 weeks after the olfaction dysfunction, while only long-term depression was impaired 1 week after the treatment. Western blot showed that the expression and phosphorylation of GluA1 in zinc group did not show any increase after fear conditioning as the control mice. Serum corticosterone release was increased in olfactory deficit mice at baseline and after acute stress when tested 3, 10 and 20 days after the olfactory dysfunction. All these results indicated that reversible olfactory dysfunction elicited impaired hippocampal function in mice. The higher corticosterone release after olfactory deficiency might serve as an underling mechanism.


Asunto(s)
Corticosterona , Hipocampo/fisiopatología , Aprendizaje por Laberinto/fisiología , Trastornos de la Memoria/fisiopatología , Plasticidad Neuronal/fisiología , Trastornos del Olfato/fisiopatología , Administración Intranasal , Animales , Corticosterona/sangre , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Trastornos de la Memoria/sangre , Trastornos de la Memoria/inducido químicamente , Ratones , Ratones Endogámicos ICR , Plasticidad Neuronal/efectos de los fármacos , Trastornos del Olfato/sangre , Trastornos del Olfato/inducido químicamente , Sulfato de Zinc/administración & dosificación , Sulfato de Zinc/toxicidad
3.
Neurobiol Learn Mem ; 173: 107224, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32246991

RESUMEN

The internal globus pallidus (GPi) is one part of basal ganglion nucleuses which play fundamental role in motor function. Recent studies indicated that GPi could modulate emotional processing and learning, but the possible mechanism remains still unknown. In this study, the effects of endopeduncular nucleus (EP, a rodent homolog of GPi) on fear conditioning were tested in rats. GABAA receptor agonist muscimol was bilaterally delivered into the EP 15 min before or immediately after fear conditioning in rats. We found that EP inactivation impaired the acquisition but not consolidation of fear memory in rats. Furthermore, the long-term potentiation (LTP) in hippocampal CA1 area was impaired, and the learning related phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit 1 (GluA1) at the Ser845 site in hippocampus was decreased in muscimol treated group. These results demonstrated that dysfunction of EP impaired hippocampal dependent learning and memory in rats.


Asunto(s)
Condicionamiento Clásico/fisiología , Núcleo Entopeduncular/fisiología , Miedo/fisiología , Hipocampo/fisiología , Plasticidad Neuronal/fisiología , Animales , Condicionamiento Clásico/efectos de los fármacos , Núcleo Entopeduncular/efectos de los fármacos , Miedo/efectos de los fármacos , Agonistas de Receptores de GABA-A/farmacología , Hipocampo/efectos de los fármacos , Masculino , Muscimol/farmacología , Plasticidad Neuronal/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
4.
Neurosci Lett ; 692: 143-149, 2019 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-30412751

RESUMEN

There is a close relationship between olfactory dysfunction and depression, but the underlying mechanism remains unknown. Studies have shown that olfactory deprived animal experience a higher level of stress compared with controls. In the present study, we aimed to investigate whether olfactory deprived mice would be more vulnerable to develop cognitive and emotional impairments under chronic stresses. Mice were treated with intranasal zinc sulfate infusion which resulted in a complete but reversible loss of olfactory function, and then they were treated with either chronic restraint stress (CRS) or chronic unpredictable mild stress (CUMS) for three consecutive weeks. After that, anxiety- and depressive-like behavior, as well as spatial learning and memory were measured. We found that olfactory deficit induced depressive-like behavior and impaired spatial learning and memory in mice, and the olfactory scores were significantly correlated with depressive-like behavior or the spatial learning. After CRS, olfactory deprived mice showed less anxiety- and depressive- like behaviors and better olfactory recovery than non-stressed anosmia mice. In contrast, CUMS led to increased anxiety- and depressive-like behavior and deterred the olfactory recovery. These results indicated that transient olfactory deprivation induces emotional and cognitive impairment in mice, which could be modulated by chronic stresses with a stressor intensity dependent way.


Asunto(s)
Ansiedad/etiología , Depresión/etiología , Olfato , Estrés Psicológico/etiología , Animales , Conducta Animal , Masculino , Ratones Endogámicos ICR , Olfato/efectos de los fármacos , Aprendizaje Espacial/efectos de los fármacos , Memoria Espacial/efectos de los fármacos , Sulfato de Zinc/administración & dosificación
5.
New Phytol ; 218(1): 167-182, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29417579

RESUMEN

RNA editing is a post-transcriptional maturation process affecting organelle transcripts in land plants. However, the molecular functions and physiological roles of RNA editing are still poorly understood. Using high-throughput sequencing, we identified 692 RNA editing sites in the Gossypium hirsutum mitochondrial genome. A total of 422 editing sites were found in the coding regions and all the edits are cytidine (C) to uridine (U) conversions. Comparative analysis showed that two editing sites in Ghatp1, C1292 and C1415, had a prominent difference in editing efficiency between fiber and ovule. Biochemical and genetic analyses revealed that the two vital editing sites were important for the interaction between the α and ß subunits of ATP synthase, which resulted in ATP accumulation and promoted cell growth in yeast. Ectopic expression of C1292, C1415, or doubly edited Ghatp1 in Arabidopsis caused a significant increase in the number of trichomes in leaves and root length. Our results indicate that editing at C1292 and C1415 sites in Ghatp1 is crucial for ATP synthase to produce sufficient ATP for cotton fiber cell elongation. This work extends our understanding of RNA editing in atp1 and ATP synthesis, and provides insights into the function of mitochondrial edited Atp1 protein in higher plants.


Asunto(s)
Adenosina Trifosfato/metabolismo , Fibra de Algodón , Mitocondrias/metabolismo , ATPasas de Translocación de Protón Mitocondriales/genética , Proteínas de Plantas/genética , Edición de ARN/genética , ARN de Planta/genética , Adenosina Difosfato/metabolismo , Secuencia de Aminoácidos , Arabidopsis/genética , ATPasas de Translocación de Protón Mitocondriales/química , ATPasas de Translocación de Protón Mitocondriales/metabolismo , Mutación/genética , Fenotipo , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Raíces de Plantas/metabolismo , Plantas Modificadas Genéticamente , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN de Planta/metabolismo , Saccharomyces cerevisiae/metabolismo , Tricomas/metabolismo
6.
Clin Exp Pharmacol Physiol ; 45(4): 335-343, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29112770

RESUMEN

Both opiates and dopamine play important roles in learning and memory. Although synergistic action between these two neurotransmitters has been found, their functional roles remain unclear. Here, low dose morphine (2.5 mg/kg) and low dose dopamine receptor agonists (apomorphine 0.05 mg/kg; SKF38393 0.01 mg/kg; bromocriptine 0.05 mg/kg), which have no effects on spatial recognition memory, were injected intraperitoneally into mice 30 minutes before a memory test in a two-trial recognition Y-maze. The Y-maze is based on the innate tendency of rodents to explore novel environments and is therefore suitable for exploring the effects of morphine on learning and memory. Our results showed that both D1-like and D2-like dopamine receptor agonists dose-dependently impaired the retrieval of spatial recognition memory in the Y-maze, and co-administration of memory ineffective doses of apomorphine (0.05 mg/kg), SKF38393 (0.01 mg/kg), or bromocriptine (0.05 mg/kg) and of morphine (2.5 mg/kg) resulted in impaired spatial recognition memory retrieval in mice. These findings suggest the existence of interactions between morphine and dopamine receptor agonists in memory processing and that activation of the dopamine system might contribute to morphine-induced impairment of memory, which could provide insight into human addiction.


Asunto(s)
Agonistas de Dopamina/farmacología , Morfina/farmacología , Reconocimiento en Psicología/efectos de los fármacos , Memoria Espacial/efectos de los fármacos , 2,3,4,5-Tetrahidro-7,8-dihidroxi-1-fenil-1H-3-benzazepina/farmacología , Animales , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Memoria Espacial/fisiología , Factores de Tiempo
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