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1.
J Chem Neuroanat ; 118: 102035, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34597812

RESUMEN

Early-life viral infections critically influence the brain development and have been variously reported to cause neuropsychiatric diseases such as Schizophrenia, Parkinson's diseases, demyelinating diseases, etc. To investigate the alterations in the dopaminergic system, myelination and associated behavioral impairments following neonatal viral infection, the viral immune activation model was created by an intraperitoneal injection of Poly I:C (5 mg/kg bw/ip) to neonatal rat pups on PND-7. The DA-D2 receptor binding was assessed in corpus striatum by using 3H-Spiperone at 3, 6 and 12 weeks of age. MOG immunolabelling was performed to check myelination stature and myelin integrity, while corpus callosum calibre was assessed by Luxol fast blue staining. Relative behavioral tasks i.e., motor activity, motor coordination and neuromuscular strength were assessed by open field, rotarod and grip strength meter respectively at 3, 6 and 12 weeks of age. Following Poly I:C exposure, a significant decrease in DA-D2 receptor binding, reduction in corpus callosum calibre and MOG immunolabelling indicating demyelination and a significant decrease in locomotor activity, neuromuscular strength and motor coordination signify motor deficits and hypokinetic influence of early life viral infection. Thus, the findings suggest that early life poly I:C exposure may cause demyelination and motor deficits by decreasing DA-D2 receptor binding affinity.


Asunto(s)
Conducta Animal/efectos de los fármacos , Vaina de Mielina/efectos de los fármacos , Neostriado/efectos de los fármacos , Neostriado/metabolismo , Poli I-C/toxicidad , Receptores de Dopamina D2/efectos de los fármacos , Animales , Animales Recién Nacidos , Cuerpo Calloso/citología , Cuerpo Calloso/efectos de los fármacos , Masculino , Actividad Motora/efectos de los fármacos , Fuerza Muscular/efectos de los fármacos , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Wistar , Espiperona/farmacología
2.
J Mol Neurosci ; 70(11): 1684-1701, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32504405

RESUMEN

Stimuli from stressful events, attention in the classroom, and many other experiences affect the functionality of the brain by changing the structure or reorganizing the connections between neurons and their communication. Modification of the synaptic transmission is a vital mechanism for generating neural activity via internal or external stimuli. Neuronal plasticity is an important driving force in neuroscience research, as it is the basic process underlying learning and memory and is involved in many other functions including brain development and homeostasis, sensorial training, and recovery from brain injury. Indeed, neuronal plasticity has been explored in numerous studies, but it is still not clear how neuronal plasticity affects the physiology and morphology of the brain. Thus, unraveling the molecular mechanisms of neuronal plasticity is essential for understanding the operation of brain functions. In this timeline review, we discuss the molecular mechanisms underlying different forms of synaptic plasticity and their association with neurodegenerative/neurological disorders as a consequence of alterations in neuronal plasticity.


Asunto(s)
Enfermedades del Sistema Nervioso/fisiopatología , Plasticidad Neuronal , Animales , Humanos , Enfermedades del Sistema Nervioso/metabolismo , Transmisión Sináptica
3.
Int J Biol Macromol ; 138: 492-503, 2019 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-31330212

RESUMEN

Apoptosis, a well-characterized and regulated cell death programme in eukaryotes plays a fundamental role in developing or later-life periods to dispose of unwanted cells to maintain typical tissue architecture, homeostasis in a spatiotemporal manner. This silent cellular death occurs without affecting any neighboring cells/tissue and avoids triggering of immunological response. Furthermore, diminished forms of apoptosis result in cancer and autoimmune diseases, whereas unregulated apoptosis may also lead to the development of a myriad of neurodegenerative diseases. Unraveling the mechanistic events in depth will provide new insights into understanding physiological control of apoptosis, pathological consequences of abnormal apoptosis and development of novel therapeutics for diseases. Here we provide a brief overview of molecular players of programmed cell death with discussion on the role of caspases, modifications, ubiquitylation in apoptosis, removal of the apoptotic body and its relevance to diseases.


Asunto(s)
Apoptosis , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Biomarcadores , Caspasas/metabolismo , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/etiología , Neoplasias/metabolismo , Procesamiento Proteico-Postraduccional , Transducción de Señal , Ubiquitinación
4.
Neurobiol Learn Mem ; 155: 379-389, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30195050

RESUMEN

Viral infection during early stage of life influences brain development and results in several neurodevelopmental disorders such as schizophrenia, autism and behavioral abnormalities. However, the mechanism through which infection causes long-term behavioral defects is not well known. To elucidate this, we have used synthetic polyinosinic-polycytidylic acid [poly (I:C)] which acts as a dsRNA molecule and interacts with toll-like receptor-3 (TLR-3) of microglia cells to evoke the immune system, thus mimicking the viral infection. Rat pups of postnatal day (PND) 7 were infused with a single dose of poly (I:C) (5 mg/kg BW) and vehicle alone to controls. When these pups grew to 3, 6 and 12 weeks, their spatial and fear conditioning memory were impaired as assessed by Morris water maze and passive avoidance test, respectively. We checked the immune activation by staining of TNF-α in the hippocampus and observed that poly (I:C) exposure elevated the number of TNF-α positive cells immediately after 12 h of infusion in one week rat and it persisted up to postnatal age of 3 and 12 weeks. Moreover, poly (I:C) significantly decreased the binding of 3H-QNB to the cholinergic receptors in the frontal cortex and hippocampus of 3 and 6 weeks rats as compared to control but did not change significantly in 12 weeks rats. RT-PCR and immunoblotting results showed that poly (I:C) exposure upregulated the expression of memory associated genes (BDNF, Arc, EGR1) at mRNA and protein level in frontal cortex and hippocampus of 3 weeks rats as compared to control. However, long-time persistence of poly (I:C) effects significantly decreased the expression of these genes in both brain regions of 12 weeks rats. Taken together, it is evident that early life exposure to poly (I:C) has a long-term effect and impairs learning and memory, probably through TNF-α mediated neuroinflammation and alteration in the expression of memory associated genes in frontal cortex and hippocampus of rats.


Asunto(s)
Encéfalo/crecimiento & desarrollo , Encéfalo/inmunología , Memoria/fisiología , Plasticidad Neuronal/genética , Plasticidad Neuronal/inmunología , Aprendizaje Espacial/fisiología , Animales , Encéfalo/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Condicionamiento Clásico/fisiología , Femenino , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/inmunología , Expresión Génica , Hipocampo/efectos de los fármacos , Hipocampo/inmunología , Masculino , Memoria/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Poli I-C/administración & dosificación , Ratas Wistar , Receptores Muscarínicos/metabolismo , Aprendizaje Espacial/efectos de los fármacos , Factor de Necrosis Tumoral alfa/metabolismo
5.
Artículo en Inglés | MEDLINE | ID: mdl-24321757

RESUMEN

A novel analytical approach based on molecularly imprinted solid phase extraction (MISPE) coupled with dispersive liquid-liquid microextraction (DLLME), and injector port silylation (IPS) has been developed for the selective preconcentration, derivatization and analysis of 3-phenoxybenzoic acid (3-PBA) using gas chromatography-tandem mass spectrometry (GC-MS/MS) in complex biological samples such as rat blood and liver. Factors affecting the synthesis of MIP were evaluated and the best monomer and cross-linker were selected based on binding affinity studies. Various parameters of MISPE, DLLME and IPS were optimized for the selective preconcentration and derivatization of 3-PBA. The developed method offers a good linearity over the calibration range of 0.02-2.5ngmg(-1) and 7.5-2000ngmL(-1) for liver and blood respectively. Under optimized conditions, the recovery of 3-PBA in liver and blood samples were found to be in the range of 83-91%. The detection limit was found to be 0.0045ngmg(-1) and 1.82ngmL(-1) in liver and blood respectively. SRM transition of 271→227 and 271→197 has been selected as quantifier and qualifier transition for 3-PBA derivative. Intra and inter-day precision for five replicates in a day and for five, successive days was found to be less than 8%. The method developed was successfully applied to real samples, i.e. rat blood and tissue for quantitative evaluation of 3-PBA. The analytical approach developed is rapid, economic, simple, eco-friendly and possess immense utility for the analysis of analytes with polar functional groups in complex biological samples by GC-MS/MS.


Asunto(s)
Benzoatos/análisis , Benzoatos/sangre , Cromatografía de Gases y Espectrometría de Masas/métodos , Microextracción en Fase Líquida/métodos , Hígado/química , Impresión Molecular , Animales , Cromatografía de Gases y Espectrometría de Masas/economía , Límite de Detección , Microextracción en Fase Líquida/economía , Ratas , Ratas Wistar , Espectrometría de Masas en Tándem/economía , Espectrometría de Masas en Tándem/métodos
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