Neonatal stress affects vulnerability of cholinergic neurons and cognition in the rat: involvement of the HPA axis.
Adverse experiences early in life may sensitize specific neurocircuits to subsequent stressors. We have evaluated in maternal separation (MS) rats, an animal paradigm of early-life stress, the effects of a selective cholinergic lesion on cognitive function as well as susceptibility of cholinergic neurons to the lesion. MS rats subjected to a cholinergic lesion by administration of the immunotoxin 192 IgG-saporin, showed significant decreases in both choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity compared to control lesioned rats. Morris water maze results revealed a significant impairment in learning and memory function in MS adult rats and further cognitive deficits after the lesion. The lesion of cholinergic neurons induced a significant decrease in glucocorticoid receptor density in MS rats, accompanied by increases in CRF mRNA expression. Decreases in NGF and increases in NGF-p75NTR expression have also been found in MS rats. Our results suggest that vulnerability of basal forebrain cholinergic nerve cells might be affected by the HPA axis. The present data are discussed not only in terms of conditions that occur during ageing or Alzheimer disease, but also regarding a purported involvement of the cholinergic system in the regulation of HPA axis activity.
Aisa
Bárbara
B
Department of Pharmacology, School of Medicine, University of Navarra, Irunlarrea 1, 31008 Pamplona, Spain.
Gil-Bea
Francisco Javier
FJ
Marcos
Beatriz
B
Tordera
Rosa
R
Lasheras
Berta
B
Del Río
Joaquín
J
Ramírez
Maria J
MJ
D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002540:Cerebral Cortex / Q000378:metabolism; D002799:Cholinergic Fibers / Q000378:metabolism*; D003071:Cognition / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D000922:Immunotoxins / Q000276:immunology*; D008297:Male; D008426:Maternal Deprivation; D020932:Nerve Growth Factor / Q000378:metabolism; D009419:Nerve Tissue Proteins; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D054789:Ribosome Inactivating Proteins, Type 1 / Q000276:immunology*; D000076985:Saporins; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology*
C085696:192 IgG-saporin; D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D009419:Nerve Tissue Proteins; D011965:Receptors, Glucocorticoid; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D054789:Ribosome Inactivating Proteins, Type 1; C068313:Ngfr protein, rat; D003346:Corticotropin-Releasing Hormone; D020932:Nerve Growth Factor; D000076985:Saporins