Developmentally-induced hypothyroidism alters the expression of Egr-1 and Arc genes and the sensitivity to cannabinoid agonists in the hippocampus. Possible implications for memory and learning.
We analyzed the role of the cannabinoid system in the cognitive deficits caused by developmentally-induced hypothyroidism. We studied in control and hypothyroid rats the effect of a cannabinoid agonist on spatial memory, hippocampal phosphorylation of CREB and expression of early genes. Our results show that, 1-basal hippocampal expression of early genes and spatial learning are decreased in hypothyroid rats; 2-hypothyroid rats are very sensitive to cannabinoid agonists. Low dose of cannabinoid agonist ineffective in controls altered spatial memory, CREB's phosphorylation and early gene expression in hypothyroids. These effects are not due a change in CB1 receptor (CB1R) content. 3-Treatment of hypothyroid rats with thyroid hormones normalized the biochemical and behavioral responses to cannabinoid agonists but did not correct the low basal levels of early gene transcripts and the deficits in spatial learning. All these data suggest that the hippocampal deregulation of early genes expression could play an important role in the basal cognitive deficits of hypothyroid rats.
Departamento de Biología Celular, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain.
Elena
E
Giné
Victor
V
Echeverry-Alzate
Jose Antonio
JA
López-Moreno
Alejandro
A
López-Jimenez
Daniel
D
Torres-Romero
Ana
A
Perez-Castillo
Angel
A
Santos
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D063386:Cannabinoid Receptor Agonists / Q000009:adverse effects; D003409:Congenital Hypothyroidism / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D004351:Drug Resistance / Q000187:drug effects; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D063388:Endocannabinoids / Q000819:agonists*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020249:Hormone Replacement Therapy; D007859:Learning Disabilities / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013037:Spatial Behavior / Q000187:drug effects; D013963:Thyroid Hormones / Q000627:therapeutic use
D063386:Cannabinoid Receptor Agonists; D003598:Cytoskeletal Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D063388:Endocannabinoids; D009419:Nerve Tissue Proteins; D013963:Thyroid Hormones; C092069:activity regulated cytoskeletal-associated protein