Efecto de la administración de anfetamina en edad infantil sobre la morfología neuronal de área del sistema límbico a edades pre-puber, puber y post -puber en la rata

"La anfetamina (ANF) es un psicoestimulante considerado un agonista indirecto dopaminérgico, utilizado ampliamente tanto de manera terapéutica como recreativa (Heal y cols., 2013). En los niños la ANF es una sustancia que se utiliza para el tratamiento de algunas patologías psiquiátricas tales como la narcolepsia y trastorno por déficit de atención e hiperactividad (TDAH), en el cual incluso es el tratamiento de primera elección a pesar de la falta de información pre-clínica y clínica que demuestren sus efectos a largo plazo (Faraone y Wilens, 2003; Tripp y Wickens, 2009; Sharma y Couture, 2014). La controversia en torno al uso de la ANF en niños es debido a que ha demostrado que la exposición a psicoestimulantes durante el neurodesarrollo puede afectar de manera importante este proceso, el cual es indispensable la generación de redes neuronales adecuadas para el correcto funcionamiento del cerebro en el individuo (Kolb y cols., 2012). Además se ha demostrado que la exposición a ANF durante el neurodesarrollo induce cambios anatómicos y fisiológicos en el sistema límbico (Robinson y Kolb, 1999; Flores y cols., 2011.

Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?

Over the past few decades, extensive research has shed light on immune alterations and the significance of dysfunctional biological barriers in psychiatric disorders. The leaky gut phenomenon, intimately linked to the integrity of both brain and intestinal barriers, may play a crucial role in the origin of peripheral and central inflammation in these pathologies. Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates both the immune response and the permeability of biological barriers. Notably, S1P-based drugs, such as fingolimod and ozanimod, have received approval for treating multiple sclerosis, an autoimmune disease of the central nervous system (CNS), and ulcerative colitis, an inflammatory condition of the colon, respectively. Although the precise mechanisms of action are still under investigation, the effectiveness of S1P-based drugs in treating these pathologies sparks a debate on extending their use in psychiatry. This comprehensive review aims to delve into the molecular mechanisms through which S1P modulates the immune system and brain/intestinal barrier functions. Furthermore, it will specifically focus on psychiatric diseases, with the primary objective of uncovering the potential of innovative therapies based on S1P signaling

Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?

Over the past few decades, extensive research has shed light on immune alterations and the significance of dysfunctional biological barriers in psychiatric disorders. The leaky gut phenomenon, intimately linked to the integrity of both brain and intestinal barriers, may play a crucial role in the origin of peripheral and central inflammation in these pathologies. Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates both the immune response and the permeability of biological barriers. Notably, S1P-based drugs, such as fingolimod and ozanimod, have received approval for treating multiple sclerosis, an autoimmune disease of the central nervous system (CNS), and ulcerative colitis, an inflammatory condition of the colon, respectively. Although the precise mechanisms of action are still under investigation, the effectiveness of S1P-based drugs in treating these pathologies sparks a debate on extending their use in psychiatry. This comprehensive review aims to delve into the molecular mechanisms through which S1P modulates the immune system and brain/intestinal barrier functions. Furthermore, it will specifically focus on psychiatric diseases, with the primary objective of uncovering the potential of innovative therapies based on S1P signaling.Ministerio de Ciencia e Innovación (España)Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM)Depto. de Farmacología y ToxicologíaFac. de MedicinaTRUEpubDescuento UC

Neuroplasticity and inflammatory alterations in the nucleus accumbens are corrected after risperidone treatment in a schizophrenia-related developmental model in rats

CRUE-CSIC (Acuerdos Transformativos 2021)Increased dopaminergic activity in the striatum underlies the neurobiology of psychotic symptoms in schizophrenia (SZ). Beyond the impaired connectivity among the limbic system, the excess of dopamine could lead to inflammation and oxidative/nitrosative stress. It has been suggested that atypical antipsychotic drugs attenuate psychosis not only due to their modulatory activity on the dopaminergic/serotonergic neurotransmission but also due to their anti-inflammatory/antioxidant effects. In such a manner, we assessed the effects of the atypical antipsychotic risperidone (RISP) on the structural neuroplasticity and biochemistry of the striatum in adult rats with neonatal ventral hippocampus lesion (NVHL), which is a developmental SZ-related model. RISP administration (0.25 mg/kg, i.p.) ameliorated the neuronal atrophy and the impairments in the morphology of the dendritic spines in the spiny projection neurons (SPNs) of the ventral striatum (nucleus accumbens: NAcc) in the NVHL rats. Also, RISP treatment normalized the pro-inflammatory pathways and induced the antioxidant activity of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in this model. Our results point to the neurotrophic, antiinflammatory, and antioxidant effects of RISP, together with its canonical antipsychotic mechanism, to enhance striatum function in animals with NVHL.Ministerio de Economía y Competitividad (MINECO)/FEDERCONACYTDepto. de Farmacología y ToxicologíaFac. de MedicinaTRUEpu

Increased suicide rates in Mexico City during the COVID-19 pandemic outbreak: An analysis spanning from 2016 to 2021

Objective: Coronavirus disease 2019 (COVID-19) has impacted mental health worldwide, and suicide can be a serious outcome of this. Thus, suicide characteristics were examined before and during the COVID-19 pandemic in Mexico City. Methods: This is a retrospective study including all Mexico City residents who had a coroner's record with a cause of death of intentional self-harm (ICD-10) from January 2016 to December 2021. Results: From 2016 to 2021, 3636 people committed suicide, of which 2869 were males (78.9%) and 767 females (21.1%). From 2016 to 2019 the suicide rate remained constant (∼6 per 100000) and dramatically increased in 2020 (10.45 per 100,000), to return to the levels of the previous year in 2021 (6.95 per 100000). The suicide rate in 2020 specifically increased from January to June (COVID-19 outbreak) in all age groups. Moreover, every year young people (15–24 years) have the maximum suicide rate and depression was the main suicide etiology. Conclusion: The COVID-19 pandemic outbreak increased the suicide rate, regardless of age, but suicide prevalence was higher in males and young people, regardless of the COVID-19 pandemic. These findings confirm that suicide is a complex and multifactorial problem and will allow the establishment of new guidelines for prevention and care strategies

Effects of amphetamine exposure during adolescence on behavior and prelimbic cortex neuron activity in adulthood

Repeated exposure to psychostimulants during adolescence produces long-lasting changes in behavior that may be mediated by disrupted development of the mesocorticolimbic dopamine system. Here, we tested this hypothesis by assessing the effects of amphetamine (AMPH) and dopamine receptor-selective drugs on behavior and neuron activity in the prelimbic region of the medial prefrontal cortex (PFC). Adolescent male, Sprague-Dawley rats were given saline or 3 mg/kg AMPH between postnatal day (P) 27 and P45. In Experiment 1, locomotor behavior was assessed during adulthood following challenges with a dopamine D1 (SKF 82958) or D2 (quinpirole) receptor-selective agonist. In Experiment 2, pre-exposed rats were challenged during adulthood with AMPH and a D1 (SKF 83566) or D2 (eticlopride) receptor-selective antagonist. In Experiment 3, the activity of putative pyramidal cells in the prelimbic cortex was recorded as rats behaved in an open-field arena before and after challenge injections with AMPH and one of the antagonists. We found that compared to controls, adolescent pre-exposed rats were more sensitive to the stimulant effects of AMPH and the dopamine receptor agonists, as well as to the ability of the antagonists to reverse AMPH-induced stereotypy. Prelimbic neurons from AMPH pre-exposed rats were also more likely to respond to an AMPH challenge in adulthood, primarily by reducing their activity, and the antagonists reversed these effects. Our results suggest that exposure to AMPH during adolescence leads to enduring adaptations in the mesocorticolimbic dopamine system that likely mediate heightened response to the drug during adulthood