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Behavioral, electrophysiological and neuropathological characteristics of the occurrence of hypertension in pregnant rats.

ABSTRACT: Pre-eclampsia (PE) affects approximately 2 to 8% of pregnant women, causing blood pressure above 140?×?90?mmHg and proteinuria, normally after the 20th gestation week. If unsuccessfully treated, PE can lead to self-limited seizures (Eclampsia) that could eventually result in death of the mother and her fetus. The present study reports an experimental model of preeclampsia hypertension in pregnant (HP) and non-pregnant (H) Wistar rats by partially clamping one of their renal arteries. Pregnant (P) and non-pregnant (C) controls were provided. Differently from controls (C and P), H and HP animals presented a steady rise in BP two weeks after renal artery clamping. Injection of pentylenetetrazol (PTZ) induced behavioral and electroencephalographic seizures in all groups, which were increased in number, duration, amplitude and power accompanied by decreased latency in HP animals (p?

SUBMITTER: Oliveira LF

PROVIDER: S-EPMC6412065 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Behavioral, electrophysiological and neuropathological characteristics of the occurrence of hypertension in pregnant rats.

Oliveira Leandro F LF Pinheiro Daniel J L L DJLL Rodrigues Laís D LD Reyes-Garcia Selvin Z SZ Nishi Erika E EE Ormanji Milene S MS Faber Jean J Cavalheiro Esper A EA

Scientific reports 20190311 1

Pre-eclampsia (PE) affects approximately 2 to 8% of pregnant women, causing blood pressure above 140 × 90 mmHg and proteinuria, normally after the 20th gestation week. If unsuccessfully treated, PE can lead to self-limited seizures (Eclampsia) that could eventually result in death of the mother and her fetus. The present study reports an experimental model of preeclampsia hypertension in pregnant (HP) and non-pregnant (H) Wistar rats by partially clamping one of their renal arteries. Pregnant (P ...[more]

PMID: 30858526

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Project description:BackgroundAnti-IgLON5 disease is a rare neurological disorder associated with autoantibodies against the neuronal cell adhesion protein, IgLON5. Cellular investigations with human IgLON5 antibodies have suggested an antibody-mediated pathogenesis, but whether human IgLON5 autoantibodies can induce disease symptoms in mice is yet to be shown. Moreover, the effects of anti-IgLON5 autoantibodies on neurons and the precise molecular mechanisms in vivo remain controversial.MethodsWe investigated the effects of anti-IgLON5 antibodies in vivo and evaluated their long-term effects. We used two independent passive-transfer animal models and evaluated the effects of the antibodies on mouse behaviors at different time points from day 1 until day 30 after IgG infusion. A wide range of behaviors, including tests of locomotion, coordination, memory, anxiety, depression and social interactions were established. At termination, brain tissue was analyzed for human IgG, neuronal markers, glial markers, synaptic markers and RNA sequencing.ResultsThese experiments showed that patient's anti-IgLON5 antibodies induced progressive and irreversible behavioral deficits in vivo. Notably, cognitive abnormality was supported by impaired average gamma power in the CA1 during novel object recognition testing. Accompanying brain tissue studies showed progressive increase of brain-bound human antibodies in the hippocampus of anti-IgLON5 IgG-injected mice, which persisted 30 days after the injection of patient's antibodies was stopped. Microglial and astrocyte density was increased in the hippocampus of anti-IgLON5 IgG-injected mice at Day 30. Whole-cell voltage clamp recordings proved that anti-IgLON5 antibodies affected synaptic homeostasis. Further western blot investigation of synaptic proteins revealed a reduction of presynaptic (synaptophysin) and post-synaptic (PSD95 and NMDAR1) expression in anti-IgLON5 IgG-injected mice.ConclusionsOverall, our findings indicated an irreversible effect of anti-IgLON5 antibodies and supported the pathogenicity of these antibodies in vivo.

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Behavioral, electrophysiological and neuropathological characteristics of the occurrence of hypertension in pregnant rats.

Publications

Behavioral, electrophysiological and neuropathological characteristics of the occurrence of hypertension in pregnant rats.

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