Maternal immune activation in rats attenuates the excitability of monoamine-secreting neurons in adult offspring in a sex-specific way

Csatlósová, Kristína; Bögi, Eszter; Durisova, Barbora; Grinchii, Daniil; Paliokha, Ruslan; Moravcikova, Lucia; Lacinová, Ľubica; Ježová, Daniela; Dremencov, Eliyahu

doi:10.1016/j.euroneuro.2020.12.002

Cited by 24 publications

(16 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, animal models of this condition employing exposure to viral or bacterial immunostimulants provide valuable insights into the basis of schizophrenia-like disturbances [ 9 , 10 , 11 ]. One of the widely implemented approaches is maternal immune activation (MIA), produced by the prenatal administration of lipopolysaccharide (LPS) [ 12 , 13 , 14 , 15 , 16 ]. When considering a neurodevelopmental model of schizophrenia, MIA with LPS has been described in terms of various behavioural disturbances, including affected sensorimotor gating [ 12 , 17 , 18 ], anxiety-like behaviour [ 13 , 19 ], social interactions [ 15 ], exploratory or locomotor activity [ 19 , 20 , 21 ] and cognitive deficits [ 22 , 23 ] as well as diverse biochemical alterations in the brains of the offspring, including the CX3CL1-CX3CR1 and CD200-CD200R pairs, which are crucial in neuron–microglia communication [ 13 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Quetiapine Ameliorates MIA-Induced Impairment of Sensorimotor Gating: Focus on Neuron-Microglia Communication and the Inflammatory Response in the Frontal Cortex of Adult Offspring of Wistar Rats

Chamera

Curzytek

Kamińska

et al. 2022

Cells

View full text Add to dashboard Cite

The maternal immune activation produced by the systemic administration of lipopolysaccharide (LPS) in rats provides valuable insights into the basis of behavioural schizophrenia-like disturbances and biochemical changes in the brains of the offspring, such as microglial activation. Regarding therapy, antipsychotics continually constitute the cornerstone of schizophrenia treatment. To their various efficacy and side effects, as well as not fully recognised mechanisms of action, further characteristics have been suggested, including an anti-inflammatory action via the impact on neuron–microglia axes responsible for inhibition of microglial activation. Therefore, in the present study, we sought to determine whether chronic treatment with chlorpromazine, quetiapine or aripiprazole could influence schizophrenia-like behavioural disturbances at the level of sensorimotor gating in male offspring prenatally exposed to LPS. Simultaneously, we wanted to explore if the chosen antipsychotics display a positive impact on the neuroimmunological parameters in the brains of these adult animals with a special focus on the ligand-receptor axes controlling neuron–microglia communication as well as pro- and anti-inflammatory factors related to the microglial activity. The results of our research revealed the beneficial effect of quetiapine on deficits in sensorimotor gating observed in prenatally LPS-exposed offspring. In terms of axes controlling neuron–microglia communication and markers of microglial reactivity, we observed a subtle impact of quetiapine on hippocampal Cx3cl1 and Cx3cr1 levels, as well as cortical Cd68 expression. Hence, further research is required to fully define and explain the involvement of quetiapine and other antipsychotics in Cx3cl1-Cx3cr1 and/or Cd200-Cd200r axes modulation and inflammatory processes in the LPS-based model of schizophrenia-like disturbances.

show abstract

Section: Introductionmentioning

confidence: 99%

Quetiapine Ameliorates MIA-Induced Impairment of Sensorimotor Gating: Focus on Neuron-Microglia Communication and the Inflammatory Response in the Frontal Cortex of Adult Offspring of Wistar Rats

Chamera

Curzytek

Kamińska

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…Further, while there are data to suggest that MIA alone alters reward behaviors in rodents, this work has almost entirely focuses on motor responses to dopamine agonists in male offspring [ 34 – 36 ]. Since dopamine activity is both decreased and increased, depending on brain region, in MIA rats [ 37 , 38 ], it is unclear if these previous data represent an “addiction” phenotype, or are simply reflective of the locomotor deficits induced by dopamine dysfunction. A more recent set of studies indicate that MIA leads to enhanced dopamine firing in the VTA in male offspring [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

“…Since dopamine activity is both decreased and increased, depending on brain region, in MIA rats [ 37 , 38 ], it is unclear if these previous data represent an “addiction” phenotype, or are simply reflective of the locomotor deficits induced by dopamine dysfunction. A more recent set of studies indicate that MIA leads to enhanced dopamine firing in the VTA in male offspring [ 38 ]. Increased VTA dopamine firing has been previously demonstrated in male alcohol-preferring (P) rats, and rodents experiencing alcohol withdrawal [ 39 ], suggesting that MIA might lead to VTA dopamine changes that enhance the risk of alcohol misuse, at least in males.…”

Section: Discussionmentioning

confidence: 99%

Maternal immune activation and adolescent alcohol exposure increase alcohol drinking and disrupt cortical-striatal-hippocampal oscillations in adult offspring

et al. 2022

View full text Add to dashboard Cite

Maternal immune activation (MIA) is strongly associated with an increased risk of developing mental illness in adulthood, which often co-occurs with alcohol misuse. The current study aimed to begin to determine whether MIA, combined with adolescent alcohol exposure (AE), could be used as a model with which we could study the neurobiological mechanisms behind such co-occurring disorders. Pregnant Sprague-Dawley rats were treated with polyI:C or saline on gestational day 15. Half of the offspring were given continuous access to alcohol during adolescence, leading to four experimental groups: controls, MIA, AE, and Dual (MIA + AE). We then evaluated whether MIA and/or AE alter: (1) alcohol consumption; (2) locomotor behavior; and (3) cortical-striatal-hippocampal local field potentials (LFPs) in adult offspring. Dual rats, particularly females, drank significantly more alcohol in adulthood compared to all other groups. MIA led to reduced locomotor behavior in males only. Using machine learning to build predictive models from LFPs, we were able to differentiate Dual rats from control rats and AE rats in both sexes, and Dual rats from MIA rats in females. These data suggest that Dual “hits” (MIA + AE) increases substance use behavior and disrupts activity in reward-related circuits, and that this may be a valuable heuristic model we can use to study the neurobiological underpinnings of co-occurring disorders. Our future work aims to extend these findings to other addictive substances to enhance the translational relevance of this model, as well as determine whether amelioration of these circuit disruptions can reduce substance use behavior.

show abstract

“…In vivo electrophysiological assessment of the excitability of 5-HT neurons of the DRN was performed as previously described [7,[42][43][44]. Adult male Wistar rats, weighing 300-350 g, were ordered from the Animal Breeding Facility of The Institute of Experimental Pharmacology and Toxicology, Center of Experimental Medicine, Slovak Academy of Sciences in DobráVoda, Slovakia.…”

Section: In Vivo Electrophysiologymentioning

confidence: 99%

Combined in silico, ex vivo, and in vivo Assessment of L-17, a Thiadiazine Derivative With Putative Neuroprotective and Antidepressant-Like Effects

Sarapultsev¹,

Vassiliev²,

Grinchii³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

L-17 is a thiadiazine derivative with putative anti-inflammatory, neuroprotective, and antidepressant-like properties. In this study, we applied combined in silico, ex vivo, and in vivo electrophysiology techniques to reveal the potential mechanism of action of L-17. PASS 10.4 Professional Extended software suggested that L-17 might have pro-cognitive, antidepressant, and antipsychotic effects. Docking energy assessment with AutoDockVina predicted that the binding affinities of L-17 to the serotonin transporter (SERT) and serotonin receptors 3 and 1A (5-HT3 and 5-HT1A) receptors are compatible to the selective serotonin reuptake inhibitor (SSRI) fluoxetine and selective antagonists of 5-HT3 and 5-HT1A receptors, granisetron and WAY100135, respectively. Acute pre-treatment with L-17 robustly increased c-Fos immunoreactivity in the amygdala (central nucleus), suggesting increased neuronal excitability in this brain area after L-17 administration. Acute L-17 also dose-dependently inhibited of 5-HT neurons of the dorsal raphe nucleus (DRN). This inhibition was partially reversed by subsequent administration of WAY100135, suggesting the involvement of extracellular 5-HT. Based on in silico predictions, c-Fos immunohistochemistry, and in vivo electrophysiology, we suggest that L-17 is a potent 5-HT reuptake inhibitor and/or partial 5-HT1A receptor antagonist. Thus, L-17 might be a representative of a new class of antidepressant drugs. Since L-17 also possesses neuro- and cardio-protective properties, it can be useful in post-stroke and post-myocardial infarction (MI) depression. In general, combined in silico predictions and ex vivo neurochemical and in vivo electrophysiological assessment might be a useful strategy for early preclinical assessment of the affectivity and neural mechanism in action of the novel CNS drugs.

show abstract

Maternal immune activation in rats attenuates the excitability of monoamine-secreting neurons in adult offspring in a sex-specific way

Cited by 24 publications

References 50 publications

Quetiapine Ameliorates MIA-Induced Impairment of Sensorimotor Gating: Focus on Neuron-Microglia Communication and the Inflammatory Response in the Frontal Cortex of Adult Offspring of Wistar Rats

Quetiapine Ameliorates MIA-Induced Impairment of Sensorimotor Gating: Focus on Neuron-Microglia Communication and the Inflammatory Response in the Frontal Cortex of Adult Offspring of Wistar Rats

Maternal immune activation and adolescent alcohol exposure increase alcohol drinking and disrupt cortical-striatal-hippocampal oscillations in adult offspring

Combined <em>in silico,</em> <em>ex vivo</em>, and <em>in vivo</em> Assessment of L-17, a Thiadiazine Derivative With Putative Neuroprotective and Antidepressant-Like Effects

Contact Info

Product

Resources

About