Elsevier

Neuroscience

Volume 168, Issue 2, 30 June 2010, Pages 416-428
Neuroscience

Cognitive, Behavioral and Systems Neuroscience
Research Paper
Vasopressinergic network abnormalities potentiate conditioned anxious state of rats subjected to maternal hyperthyroidism

https://doi.org/10.1016/j.neuroscience.2010.03.059Get rights and content

Abstract

We have previously reported that a mild maternal hyperthyroidism in rats impairs stress coping of adult offspring. To assess anxiogenesis in this rat model of stress over-reactivity, we used two behavioural tests for unconditional and conditional anxious states: elevated plus maze test (EPM) and Vogel conflict test (VCT). In the latter one, arginine vasopressin (AVP) release was enhanced due to osmotic stress. With the EPM test no differences were observed between maternal hyperthyroid rats (MH) and controls. However, with the VCT, the MH showed increased anxiety-like behaviour. This behavioural difference was abolished by diazepam. Plasma AVP concentration curve as a function of water deprivation (WD) time showed a marked increase, reaching its maximal levels within half the time of controls and another significant difference after VCT. A general increase in Fos expression in hypothalamic supraoptic and paraventricular nuclei (PVN) was observed during WD and after VCT. There was also a significant increase of AVP immunoreactivity in anterior hypothalamic area. A large number of Herring bodies were observed in the AVP containing fibres of MH hypothalamic-neurohypophysial system. Numerous reciprocal synaptic connections between AVP and corticotropin releasing factor containing neurons in MH ventromedial PVN were observed by electron microscopy. These results suggest that a mild maternal hyperthyroidism could induce an aberrant organization in offspring's hypothalamic stress related regions which could mediate the enhanced anxiety seen in this animal model.

Section snippets

Animals

Wistar rats were used in this study. All animal procedures were approved by the local bioethical and biosecurity committees in accordance with the principles exposed in the Handbook for the Use of Animals in Neuroscience Research (Society for Neuroscience. Washington, D.C.1991). Animals were housed on a 12-h light schedule in a room with temperature between 20 and 24 °C with adequate ventilation and given access to standard rat chow and water ad libitum, unless otherwise specified.

The breeding

Significantly potentiated anxious state in MH occurred only after water deprivation

Unconditioned and conditioned anxious states were assessed using two well-validated behavioural tests, the EPM and the VCT. EPM evaluates the exploration versus avoidance state placing the rat in an unconditioned environment with the closed arm representing safety and the open-elevated arm denoting novelty, though risky. Diminished time spent in the open arm and reduced number of entries implies higher unconditioned anxious state. The MH showed no significant differences in these two measured

Discussion

Maternal hyperthyroidism due to Grave's disease and gestational transient thyrotoxicosis is a common endocrine condition during human pregnancy. Besides, inadequate doses for hormone replacement and insufficient monitoring could also put the fetal development under an iatrogenic hyperthyroid environment. In consonance with our previous study reporting that maternal hyperthyroid offspring possess a more reactive neuroendocrinological stress-coping system (Zhang et al., 2008), the results from

Conclusion

In conclusion, the initial EM observation of the reciprocal synaptic connections between AVP and CRF containing neurons in the hypothalamic paraventricular region from this study suggests the existence of synaptic pathways between these two main stress-coping related neuropeptidergic systems in stress over-reactive MH. Hence, our findings open a potential research area for the investigation of the anatomo-functional substrates underlying stress related emotional disturbances in MH offspring.

Acknowledgments

This study was supported by grants: UNAM IN210406, IN224407; CONACYT: 49704, 79641. LZ was on sabbatical leave at MRC Anatomical Neuropharmacology Unit, Oxford University—hospitality from Peter Somogyi and fellowships from DGAPA-UNAM and CONACYT Mexico are greatly acknowledged. MPM, VSH and FSE were supported by DGAPA-UNAM undergraduate scholarships. We would like to thank Paul Bolam (Oxford), Francesco Ferraguti (Innsbruck) and Teresa Morales (INB, UNAM), for critical reading of the

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