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1.
Front Psychiatry ; 15: 1320650, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38645418

RESUMEN

Aim: Schizophrenia involves complex interactions between biological and environmental factors, including childhood trauma, cognitive impairments, and premorbid adjustment. Predicting its severity and progression remains challenging. Biomarkers like glial cell line-derived neurotrophic factor (GDNF) and miRNA-29a may bridge biological and environmental aspects. The goal was to explore the connections between miRNAs and neural proteins and cognitive functioning, childhood trauma, and premorbid adjustment in the first episode of psychosis (FEP). Method: This study included 19 FEP patients who underwent clinical evaluation with: the Childhood Trauma Questionnaire (CTQ), the Premorbid Adjustment Scale (PAS), the Positive and Negative Syndrome Scale (PANSS), and the Montreal Cognitive Assessment Scale (MoCA). Multiplex assays for plasma proteins were conducted with Luminex xMAP technology. Additionally, miRNA levels were quantitatively determined through RNA extraction, cDNA synthesis, and RT-qPCR on a 7500 Fast Real-Time PCR System. Results: Among miRNAs, only miR-29a-3p exhibited a significant correlation with PAS-C scores (r = -0.513, p = 0.025) and cognitive improvement (r = -0.505, p = 0.033). Among the analyzed proteins, only GDNF showed correlations with MoCA scores at the baseline and after 3 months (r = 0.533, p = 0.0189 and r = 0.598, p = 0.007), cognitive improvement (r = 0.511, p = 0.025), and CTQ subtests. MIF concentrations correlated with the PAS-C subscale (r = -0.5670, p = 0.011). Conclusion: GDNF and miR-29a-3p are promising as biomarkers for understanding and addressing cognitive deficits in psychosis. This study links miRNA and MIF to premorbid adjustment and reveals GDNF's unique role in connection with childhood trauma.

2.
Pharmacol Rep ; 76(3): 452-462, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38649593

RESUMEN

The global prevalence of overweight and obesity is a significant public health concern that also largely affects women of childbearing age. Human epidemiological studies indicate that prenatal exposure to excessive maternal weight or excessive gestational weight gain is linked to various neurodevelopmental disorders in children, including attention deficit hyperactivity disorder, autism spectrum disorder, internalizing and externalizing problems, schizophrenia, and cognitive/intellectual impairment. Considering that inadequate maternal body mass can induce serious disorders in offspring, it is important to increase efforts to prevent such outcomes. In this paper, we review human studies linking excessive maternal weight and the occurrence of mental disorders in children.


Asunto(s)
Efectos Tardíos de la Exposición Prenatal , Humanos , Embarazo , Femenino , Trastornos Mentales/epidemiología , Trastornos Mentales/etiología , Niño , Trastornos del Neurodesarrollo/epidemiología , Trastornos del Neurodesarrollo/etiología , Ganancia de Peso Gestacional , Obesidad/epidemiología
3.
Nutrients ; 14(11)2022 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-35683984

RESUMEN

A high-calorie diet has contributed greatly to the prevalence of overweight and obesity worldwide for decades. These conditions also affect pregnant women and have a negative impact on the health of both the woman and the fetus. Numerous studies indicate that an unbalanced maternal diet, rich in sugars and fats, can influence the in utero environment and, therefore, the future health of the child. It has also been shown that prenatal exposure to an unbalanced diet might permanently alter neurotransmission in offspring. In this study, using a rat model, we evaluated the effects of a maternal high-sugar diet on the level of extracellular glutamate and the expression of key transporters crucial for maintaining glutamate homeostasis in offspring. Glutamate concentration was assessed in extracellular fluid samples collected from the medial prefrontal cortex and hippocampus of male and female offspring. Analysis showed significantly increased glutamate levels in both brain structures analyzed, regardless of the sex of the offspring. These changes were accompanied by altered expression of the EAAT1, VGLUT1, and xc- proteins in these brain structures. This animal study further confirms our previous findings that a maternal high-sugar diet has a detrimental effect on the glutamatergic system.


Asunto(s)
Ácido Glutámico , Efectos Tardíos de la Exposición Prenatal , Animales , Encéfalo/metabolismo , Dieta , Dieta Alta en Grasa , Femenino , Ácido Glutámico/metabolismo , Homeostasis , Humanos , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratas , Azúcares
4.
Mol Neurobiol ; 59(9): 5695-5721, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35773600

RESUMEN

The problem of an unbalanced diet, overly rich in fats, affects a significant proportion of the population, including women of childbearing age. Negative metabolic and endocrine outcomes for offspring associated with maternal high-fat diet during pregnancy and/or lactation are well documented in the literature. In this paper, we present our findings on the little-studied effects of this diet on NMDA receptors and cognitive functions in offspring. The subject of the study was the rat offspring born from dams fed a high-fat diet before mating and throughout pregnancy and lactation. Using a novel object location test, spatial memory impairment was detected in adolescent offspring as well as in young adult female offspring. The recognition memory of the adolescent and young adult offspring remained unaltered. We also found multiple alterations in the expression of the NMDA receptor subunits, NMDA receptor-associated scaffolding proteins, and selected microRNAs that regulate the activity of the NMDA receptor in the medial prefrontal cortex and the hippocampus of the offspring. Sex-dependent changes in glutamate levels were identified in extracellular fluid obtained from the medial prefrontal cortex and the hippocampus of the offspring. The obtained results indicate that a maternal high-fat diet during pregnancy and lactation can induce in the offspring memory disturbances accompanied by alterations in NMDA receptor expression.


Asunto(s)
Dieta Alta en Grasa , Efectos Tardíos de la Exposición Prenatal , Animales , Dieta Alta en Grasa/efectos adversos , Femenino , Lactancia/metabolismo , Trastornos de la Memoria , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratas , Receptores de N-Metil-D-Aspartato , Memoria Espacial
5.
FASEB J ; 35(5): e21547, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33855764

RESUMEN

Cognitive impairment affects patients suffering from various neuropsychiatric diseases, which are often accompanied by changes in the glutamatergic system. Epidemiological studies indicate that predispositions to the development of neuropsychiatric diseases may be programmed prenatally. Mother's improper diet during pregnancy and lactation may cause fetal abnormalities and, consequently, predispose to diseases in childhood and even adulthood. Considering the prevalence of obesity in developed countries, it seems important to examine the effects of diet on the behavior and physiology of future generations. We hypothesized that exposure to sugar excess in a maternal diet during pregnancy and lactation would affect memory as the NMDA receptor-related processes. Through the manipulation of the sugar amount in the maternal diet in rats, we assessed its effect on offspring's memory. Then, we evaluated if memory alterations were paralleled by molecular changes in NMDA receptors and related modulatory pathways in the prefrontal cortex and the hippocampus of adolescent and young adult female and male offspring. Behavioral studies have shown sex-related changes like impaired recognition memory in adolescent males and spatial memory in females. Molecular results confirmed an NMDA receptor hypofunction along with subunit composition abnormalities in the medial prefrontal cortex of adolescent offspring. In young adults, GluN2A-containing receptors were dominant in the medial prefrontal cortex, while in the hippocampus the GluN2B subunit contribution was elevated. In conclusion, we demonstrated that a maternal high-sugar diet can affect the memory processes in the offspring by disrupting the NMDA receptor composition and regulation in the medial prefrontal cortex and the hippocampus.


Asunto(s)
Disfunción Cognitiva/patología , Azúcares de la Dieta/efectos adversos , Regulación de la Expresión Génica/efectos de los fármacos , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/patología , Receptores de N-Metil-D-Aspartato/metabolismo , Memoria Espacial/efectos de los fármacos , Animales , Disfunción Cognitiva/inducido químicamente , Femenino , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/genética
6.
Behav Brain Res ; 370: 111945, 2019 09 16.
Artículo en Inglés | MEDLINE | ID: mdl-31100299

RESUMEN

Literature data show diverse vulnerability to the rewarding effects of cocaine in human as well as in laboratory animals. The molecular mechanisms of these differences have not been discovered yet. While the initial effects of cocaine depend primarily on the dopamine system, numerous studies have shown that adaptation within the glutamatergic system is responsible for the development of addiction. In this paper, we used the unbiased conditioned place preference (CPP) to identify rats showing a vulnerable or resistant phenotype to the rewarding effects of cocaine. Next, we investigated the expression of membrane glutamate transporter proteins: GLT-1 and xCT in selected brain structures in the above-mentioned groups of rats. Moreover, we determined the nuclear level of NF-κB and Nrf2 to verify whether changes in GLT-1 and xCT expression correlate with NF-κB and Nrf2 levels, respectively. In addition, we determined GLT-1, NF-κB, xCT and Nrf2 mRNA levels to verify the involvement of transcriptional mechanisms. We also analyzed the ability of the ß-lactam antibiotic, ceftriaxone, to attenuate the persistence of CPP after a cocaine-free period in animals showing vulnerability to cocaine rewarding effects, and furthermore we determined GLT-1, xCT, NF-κB and Nrf2 protein expression. Our findings demonstrated molecular and neurochemical differences in the response to cocaine administration that are characteristic of the phenotype vulnerable or resistant to the rewarding effects of cocaine. Moreover, repeated administrations of ceftriaxone during cocaine-free perios attenuated CPP persistence and normalized GLT-1 level in the NAc. The results suggest the a lack of NF-κB involvement in the regulation of GLT-1 expression by ceftriaxone in the NAc. Additionally, we are the first to report that ceftriaxone strongly upregulates the GLT-1 in the HIP in a transcriptional mechanism involving the Nf-κB transcription factor. Future experiments may resolve the question concerning whether modulation exclusively of the GLT-1 expression in the HIP may attenuate cocaine-induced place preference or relapse.


Asunto(s)
Ceftriaxona/farmacología , Cocaína/metabolismo , Transportador 2 de Aminoácidos Excitadores/genética , Sistemas de Transporte de Aminoácidos Acídicos/metabolismo , Animales , Biomarcadores Farmacológicos/metabolismo , Encéfalo/efectos de los fármacos , Ceftriaxona/metabolismo , Cocaína/farmacología , Trastornos Relacionados con Cocaína/metabolismo , Comportamiento de Búsqueda de Drogas/efectos de los fármacos , Transportador 2 de Aminoácidos Excitadores/metabolismo , Regulación de la Expresión Génica/genética , Ácido Glutámico/genética , Ácido Glutámico/metabolismo , Masculino , Factor 2 Relacionado con NF-E2/genética , FN-kappa B/genética , Núcleo Accumbens/efectos de los fármacos , Ratas , Ratas Wistar , Recompensa , Autoadministración
7.
Pharmacol Rep ; 69(5): 1073-1081, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28988614

RESUMEN

BACKGROUND: In the cocaine addiction the development from transient into persistent neuroplastic changes strongly involves the glutamatergic system. In this respect, among glutamatergic receptors special attention is paid to the group II of metabotropic glutamatergic receptors (mGlu2/3R) which are involved in the transition from drug use to drug addiction including the relapse mechanisms. METHODS: The present study employed radioligand binding and Western blot assays to study mGlu2/3R density, affinity and protein expression in selected rat brain areas after cocaine self-administration, extinction training and cocaine-induced reinstatement. Rats were randomly assigned in triads to one of three conditions: contingent cocaine intravenous self-administration, non-contingent injections of cocaine (yoked cocaine), or saline yoked to the intake of the self-administering subject. RESULTS: Cocaine self-administration and yoked cocaine delivery resulted in a significant increase in the mGlu2/3R density in the prefrontal cortex and the dorsal striatum, while 10-day extinction training provoked a reduction in the prefrontal cortex and the nucleus accumbens. Cocaine abstinence also enhanced an increase in the [3H]ligand binding to mGlu2/3R in the prefrontal cortex. During reinstatement the cocaine challenge dose (10mg/kg, ip) led to important elevation in the mGlu2/3R density in the prefrontal cortex. CONCLUSIONS: Our study demonstrated the role of mGlu2/3R localized in the prefrontal cortex-striatum pathways to cocaine repeated exposure.


Asunto(s)
Trastornos Relacionados con Cocaína/metabolismo , Cocaína/administración & dosificación , Plasticidad Neuronal/efectos de los fármacos , Receptores de Glutamato Metabotrópico/metabolismo , Animales , Membrana Celular , Extinción Psicológica/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Glutamatos , Masculino , Ratas , Ratas Wistar , Receptores de Glutamato Metabotrópico/genética
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