Prenatal stress alters Fos protein expression in hippocampus and locus coeruleus stress-related brain structures.
Prenatal stress (PS) durably influences responses of rats from birth throughout life by inducing deficits of the hypothalamo-pituitary-adrenal (HPA) axis feedback. The neuronal mechanisms sustaining such alterations are still unknown. The purpose of the present study was to determine whether in PS and control rats, the exposure to a mild stressor differentially induces Fos protein in hippocampus and locus coeruleus, brain areas involved in the feedback control of the HPA axis. Moreover, Fos protein expression was also evaluated in the hypothalamic paraventricular nucleus (PVN) that reflect the magnitude of the hormonal response to stress. Basal plasma corticosterone levels were not different between the groups, while, PS rats exhibited higher number of Fos-immunoreactive neurons than controls, in the hippocampus and locus coeruleus in basal condition. A higher basal expression of a marker of GABAergic synapses, the vGAT, was also observed in the hypothalamus of PS rats. Fifteen minutes after the end of the exposure to the open arm of the elevated plus-maze (mild stress) a similar increased plasma corticosterone levels was observed in both groups in parallel with an increased number of Fos-immunoreactive neurons in the PVN. Return to basal plasma corticosterone values was delayed only in the PS rats. On the contrary, after stress, no changes in Fos-immunoreactivity were observed in the hippocampus and locus coeruleus of PS rats compared to basal condition. After stress, only PS rats presented an elevation of the number of activated catecholaminergic neurons in the locus coeruleus. In conclusion, these results suggest for the first time that PS alters the neuronal activation of hippocampus and locus coeruleus implicated in the feedback mechanism of the HPA axis. These data give anatomical substrates to sustain the HPA axis hyperactivity classically described in PS rats after stress exposure.
Viltart
Odile
O
Laboratory of Perinatal Stress, JE2365, University of Lille 1, 59655 Villeneuve d'Ascq, France.
Mairesse
Jérôme
J
Darnaudéry
Muriel
M
Louvart
Hélène
H
Vanbesien-Mailliot
Christel
C
Catalani
Assia
A
Maccari
Stefania
S
D000818:Animals; D003345:Corticosterone / Q000097:blood; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000166:cytology / Q000378:metabolism; D008125:Locus Coeruleus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D013315:Stress, Psychological / Q000378:metabolism*; D014018:Tissue Distribution; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
D016760:Proto-Oncogene Proteins c-fos; C118623:Slc32a1 protein, rat; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D003345:Corticosterone