Paliperidone Reversion of Maternal Immune Activation-Induced Changes on Brain Serotonin and Kynurenine Pathways

MacDowell, Karina S.; Munarriz-Cuezva, Eva; Meana, J. Javier; Leza, Juan C.; Ortega, Jorge E.

doi:10.3389/fphar.2021.682602

Cited by 11 publications

(4 citation statements)

References 92 publications

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“…Additionally, the effects observed in the offspring of Poly: IC-treated mothers regarding the DA system dysfunctions have a transgenerational impact, showing altered methylation patterns on the TH and nuclear receptor-related 1 protein (Nurr1) genes relevant for the DA functions [62]. Regarding the 5-HT signaling in the offspring of Poly: IC-treated mothers, reports showed decreased levels of this neurotransmitter in the frontal cortex and that the expression of 5-HT receptor 2A (5-HT 2A R) was increased, while no difference was found in the expression of 5-HT 1A R, 5-HT 1B R, 5-HT 2B R and 5-HT 7 R [63]. As described for the DA system, the alteration of 5-HT is related to SCZ.…”

Section: Hrsv Infection During Gestation: Possible Impairment Of Fetal Neurodevelopment?mentioning

confidence: 99%

Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

2021

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Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations. Here, we will review the potential effect of hRSV in brain development and the potential long-term neurological sequelae.

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Section: Hrsv Infection During Gestation: Possible Impairment Of Fetal Neurodevelopment?mentioning

confidence: 99%

Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

2021

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“…Furthermore, in experimental animal models, it is shown that MIA or maternal stress during pregnancy altered maternal and fetal KP metabolites [ 3 , 234 , 235 ]. Recent evidence has been accumulated on the impact of long-lasting changes of KP metabolites in the offspring involved in neuropathological and behavioral deficits ( Table 2 ) [ 3 , 5 , 23 , 130 , 138 , 139 , 165 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 , 245 , 246 , 247 , 248 , 249 , 250 , 251 , 252 ].…”

Section: Experimental Animal Models With Pre- and Postnatal Kp Confus...mentioning

confidence: 99%

Maternal Inflammation with Elevated Kynurenine Metabolites Is Related to the Risk of Abnormal Brain Development and Behavioral Changes in Autism Spectrum Disorder

Murakami

Imamura

Kasahara

et al. 2023

Cells

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Several studies show that genetic and environmental factors contribute to the onset and progression of neurodevelopmental disorders. Maternal immune activation (MIA) during gestation is considered one of the major environmental factors driving this process. The kynurenine pathway (KP) is a major route of the essential amino acid L-tryptophan (Trp) catabolism in mammalian cells. Activation of the KP following neuro-inflammation can generate various endogenous neuroactive metabolites that may impact brain functions and behaviors. Additionally, neurotoxic metabolites and excitotoxicity cause long-term changes in the trophic support, glutamatergic system, and synaptic function following KP activation. Therefore, investigating the role of KP metabolites during neurodevelopment will likely promote further understanding of additional pathophysiology of neurodevelopmental disorders, including autism spectrum disorder (ASD). In this review, we describe the changes in KP metabolism in the brain during pregnancy and represent how maternal inflammation and genetic factors influence the KP during development. We overview the patients with ASD clinical data and animal models designed to verify the role of perinatal KP elevation in long-lasting biochemical, neuropathological, and behavioral deficits later in life. Our review will help shed light on new therapeutic strategies and interventions targeting the KP for neurodevelopmental disorders.

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“…Moreover, altered 5-HT-ergic axonal circuit formation in fetal brains was found in [ 237 ]. MacDowell and coworkers [ 238 ] reported increased protein expression of the serotonin transporter (SERT) and 5-HT 2A and decreased levels of 5-HT 2C receptors with changed levels of kynurenic pathway compounds.…”

Section: Neurodevelopmental Modelsmentioning

confidence: 99%

Advantages and Limitations of Animal Schizophrenia Models

Białoń

Wąsik

2022

IJMS

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Mental illness modeling is still a major challenge for scientists. Animal models of schizophrenia are essential to gain a better understanding of the disease etiopathology and mechanism of action of currently used antipsychotic drugs and help in the search for new and more effective therapies. We can distinguish among pharmacological, genetic, and neurodevelopmental models offering various neuroanatomical disorders and a different spectrum of symptoms of schizophrenia. Modeling schizophrenia is based on inducing damage or changes in the activity of relevant regions in the rodent brain (mainly the prefrontal cortex and hippocampus). Such artificially induced dysfunctions approximately correspond to the lesions found in patients with schizophrenia. However, notably, animal models of mental illness have numerous limitations and never fully reflect the disease state observed in humans.

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Paliperidone Reversion of Maternal Immune Activation-Induced Changes on Brain Serotonin and Kynurenine Pathways

Cited by 11 publications

References 92 publications

Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection

Maternal Inflammation with Elevated Kynurenine Metabolites Is Related to the Risk of Abnormal Brain Development and Behavioral Changes in Autism Spectrum Disorder

Advantages and Limitations of Animal Schizophrenia Models

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