Prenatal lipopolysaccharide induces hypothalamic dopaminergic hypoactivity and autistic-like behaviors: Repetitive self-grooming and stereotypies

Kirsten, Thiago Berti; Bernardi, Maria Martha

doi:10.1016/j.bbr.2017.05.013

Cited by 49 publications

(40 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…After repeated restraint stress, the grooming behaviour of the HI mice was increased, and a decreased hypothalamic dopaminergic activity was observed when compared to the LI mice. Similar results were obtained when repetitive grooming was examined in an animal model of autism, where a hypoactivity hypothalamic dopaminergic activity parallel to increased repetitive grooming was observed (Kirsten & Bernardi, 2017). In addition to our results, the levels of corticosterone was increased in HI relative to LI group immediately after stress and not 1 hr after, similarly to the results observed by Kruk et al (1998).…”

Section: Without Stresssupporting

confidence: 91%

“…Finally, as the catecholamine dopamine play an important role in grooming behaviour (Hartgraves & Randall, 1986;Taylor et al, 2010;Kirsten & Bernardi, 2017), we collected the prefrontal cortex, the hypothalamus and the midbrain for neurotransmitter measures (a) without stress, (b) after 3 days of restraint stress, and (c) 1 hr after the 3 days protocol of restraint stress.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Stress resilience evidenced by grooming behaviour and dopamine levels in male mice selected for high and low immobility using the tail suspension test

Reis-Silva

Sandini

Calefi

et al. 2019

Eur J of Neuroscience

View full text Add to dashboard Cite

Grooming behaviour has different functions on many species during development and can be observed and affected during periods of stress. By selecting male mice with high (HI) and low (LI) immobility traits in the tail suspension test, a screening for antidepressant drugs, we investigate how these phenotypes associated with grooming behaviour may be influenced by the effects of repeated restraint stress. For this we used the sucrose preference test and the splash test in a novel and a familiar cage performed before and after exposure to 2 days of restraint stress. Animals were submitted to an additional day of restraint stress before the hypothalamus, prefrontal cortex and midbrain extraction for dopamine activity analysis. Corticosterone analysis was made in three distinct moments: without stress (prior first restraint session), immediately after the last restrain, and 1 hr after the last restrain episode. Compared to LI group, HI animals exhibited an increased frequency and decreased time of grooming in the familiar cage. In the novel cage, stress increased frequency and time of grooming of HI animals compared to LI. Corticosterone levels were increased in HI animals after 3 days of stress. Lower hypothalamic dopaminergic activity without stress and decreased hypothalamic dopaminergic activity immediately after stress in HI group were observed. The HI group displayed decreased prefrontal cortex dopaminergic activity and increased activity in the mesolimbic area. We proposed that through the influence of stress the two phenotypes manifested as a resilient (LI) and a not resilient (HI) trait in response to restraint stress.

show abstract

Section: Without Stresssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Stress resilience evidenced by grooming behaviour and dopamine levels in male mice selected for high and low immobility using the tail suspension test

Reis-Silva

Sandini

Calefi

et al. 2019

Eur J of Neuroscience

View full text Add to dashboard Cite

show abstract

“…33 Additionally, male fetuses have been shown to possess lower mesencephalic TH immunoreactivity, 34 and greater midbrain DA uptake 35 showed that prenatal lipopolysaccharide (LPS) exposure induced sex-dependent behavioral abnormalities (males are more affected than females) and reduced in a sex-dependent manner hypothalamic dopaminergic metabolite levels (homovanillic acid, HVA) and the hypothalamic dopaminergic turnover rate (HVA/dopamine). 38 Consistently, hypothalamus of Poly I:C-treated mice displays significant global DNA hypomethylation. 39 The hypothalamus displays developmental sex dimorphism and is involved in sexual differentiation and gonadal hormone synthesis 40 ; thus, a contribution to sex-related MIA-induced deficits is likely.…”

Section: Discussionmentioning

confidence: 93%

“…Studies have highlighted that dysfunctions in dopamine transmission are not restricted to the meso‐corticolimbic pathway but might involve the hypothalamus as well. Hence, Kirsten et al showed that prenatal lipopolysaccharide (LPS) exposure induced sex‐dependent behavioral abnormalities (males are more affected than females) and reduced in a sex‐dependent manner hypothalamic dopaminergic metabolite levels (homovanillic acid, HVA) and the hypothalamic dopaminergic turnover rate (HVA/dopamine) . Consistently, hypothalamus of Poly I:C‐treated mice displays significant global DNA hypomethylation .…”

Section: Discussionmentioning

confidence: 99%

The PPARα agonist fenofibrate attenuates disruption of dopamine function in a maternal immune activation rat model of schizophrenia

et al. 2018

View full text Add to dashboard Cite

Summary Aims Prenatal maternal immune activation (MIA) is associated with a risk to develop schizophrenia and affects dopamine systems in the ventral tegmental area (VTA), key region in the neurobiology of psychoses. Considering the well‐described sex differences in schizophrenia, we investigated whether sex affects MIA impact on dopamine system and on schizophrenia‐related behavioral phenotype. Furthermore, considering peroxisome proliferator‐activated receptor‐α (PPARα) expression in the CNS as well as its anti‐inflammatory and neuroprotective properties, we tested if PPARα activation by prenatal treatment with a clinically available fibrate (fenofibrate) may mitigate MIA‐related effects. Methods We induced MIA in rat dams with polyriboinosinic‐polyribocytidylic acid (Poly I:C) and assessed prepulse inhibition and dopamine neuron activity in the VTA by means of electrophysiological recordings in male and female preweaned and adult offspring. Results Poly I:C‐treated males displayed prepulse inhibition deficits, reduced number and firing rate of VTA dopamine neurons, and paired‐pulse facilitation of inhibitory and excitatory synapses. Prenatal fenofibrate administration attenuated detrimental effects induced by MIA on both the schizophrenia‐like behavioral phenotype and dopamine transmission in male offspring. Conclusion Our study confirms previous evidence that females are less susceptible to MIA and highlights PPARα as a potential target for treatments in schizophrenia .

show abstract

“…To investigate the effects of in utero exposure of the fetus to a maternal immune activation (MIA), various animal models have been designed (Dean et al 2015;Giovanoli, Notter, et al 2015;Solek et al 2018;Bilbo et al 2018). Injection in pregnant rodents of cytokines (Smith et al 2007), bacterial cell wall endotoxin lipopolysaccharide (LPS) (Custódio et al 2018;Kirsten and Bernardi 2017), or the viral mimic double-stranded RNA polyinosinic-polycytidylic acid (Poly(I:C)) generate offspring with a variety of autistic-like behavioral impairments (Smith et al 2007;Meyer et al 2008;Hsiao and Patterson 2011). Indeed, pregnant mice exposed to Poly(I:C) on embryonic day 12.5 (E12.5) deliver offspring that in adulthood display the 3 core symptoms of autism: reduced sociability, impaired communication skills, and stereotypic behaviors (Malkova et al 2012).…”

Section: Introductionmentioning

confidence: 99%

The GABA Developmental Shift Is Abolished by Maternal Immune Activation Already at Birth

et al. 2018

View full text Add to dashboard Cite

Epidemiological and experimental studies suggest that maternal immune activation (MIA) leads to developmental brain disorders, but whether the pathogenic mechanism impacts neurons already at birth is not known. We now report that MIA abolishes in mice the oxytocin-mediated delivery γ-aminobutyric acid (GABA) shift from depolarizing to hyperpolarizing in CA3 pyramidal neurons, and this is restored by the NKCC1 chloride importer antagonist bumetanide. Furthermore, MIA hippocampal pyramidal neurons at birth have a more exuberant apical arbor organization and increased apical dendritic length than age-matched controls. The frequency of spontaneous glutamatergic postsynaptic currents is also increased in MIA offspring, as well as the pairwise correlation of the synchronized firing of active cells in CA3. These alterations produced by MIA persist, since at P14–15 GABA action remains depolarizing, produces excitatory action, and network activity remains elevated with a higher frequency of spontaneous glutamatergic postsynaptic currents. Therefore, the pathogenic actions of MIA lead to important morphophysiological and network alterations in the hippocampus already at birth.

show abstract

Prenatal lipopolysaccharide induces hypothalamic dopaminergic hypoactivity and autistic-like behaviors: Repetitive self-grooming and stereotypies

Cited by 49 publications

References 55 publications

Stress resilience evidenced by grooming behaviour and dopamine levels in male mice selected for high and low immobility using the tail suspension test

Stress resilience evidenced by grooming behaviour and dopamine levels in male mice selected for high and low immobility using the tail suspension test

The PPARα agonist fenofibrate attenuates disruption of dopamine function in a maternal immune activation rat model of schizophrenia

The GABA Developmental Shift Is Abolished by Maternal Immune Activation Already at Birth

Contact Info

Product

Resources

About