TY - JOUR
T1 - Effects on hippocampus of lifelong absence of glucocorticoids in the pro-opiomelanocortin null mutant mouse reveal complex relationship between glucocorticoids and hippocampal structure and function
AU - Ostwald, Dirk
AU - Karpac, Jason
AU - Hochgeschwender, Ute
N1 - Funding Information:
Molecular, Cell, and Developmental Biology Program, Oklahoma Medical Research Foundation (OMRF), Oklahoma City, OK 73104
Funding Information:
POMC wild-type and mutant mice in the 129SvEv background (Yaswen et al., 1999) were housed under a 12-h light/12-h dark cycle, with standard laboratory diet (PMI5053, Purina Mills, Richmond, IN), provided ad libitum unless otherwise stated. Mice were genotyped by PCR analysis of tail DNA (Yaswen et al., 1999). All procedures described below follow NIH guidelines and were approved by the Institutional Animal Care and Use Committee of the Oklahoma Medical Research Foundation.
PY - 2006
Y1 - 2006
N2 - In humans changes in serum cortisol levels have been observed with aging, stress, and with affective disorders such as major depression and post-traumatic stress disorder. Corticosteroids are known to influence hippocampal structure and function; specifically, plasma corticosteroid levels have been inversely correlated with hippocampal cell proliferation, cell death, and impaired memory function. The relationship between corticosteroids and structure and function of the hippocampus has been studied in experimental systems in adult animals by increasing or decreasing corticosterone levels through pharmacological supplementation and through surgical removal of the adrenal gland. Here, we utilized the genetically engineered pro-opiomelanocortin (POMC) null mutant mouse, which because of the lack of all POMC peptides has no corticosterone from birth throughout life. The effect of this lifelong absence of corticosterone on the dentate gyrus of the hippocampus is a decrease in granule cell density, which correlated with a decrease in cell proliferation but not an increase in cell degeneration. Fine morphology of granule cells was unaltered. Analyses of gene expression revealed no changes in POMC null mutant vs wild-type hippocampus with respect to levels of expression of corticoid receptor genes or genes known to be regulated by corticosterone. Spatial learning as tested by the Morris water maze was not altered in the POMC null mutant mouse. Taken together with findings from other studies of the effects of altered levels of corticosteroids on the hippocampus, our results argue for a complex homeostasis in which disturbances of any one factor can offset the system in varying ways.
AB - In humans changes in serum cortisol levels have been observed with aging, stress, and with affective disorders such as major depression and post-traumatic stress disorder. Corticosteroids are known to influence hippocampal structure and function; specifically, plasma corticosteroid levels have been inversely correlated with hippocampal cell proliferation, cell death, and impaired memory function. The relationship between corticosteroids and structure and function of the hippocampus has been studied in experimental systems in adult animals by increasing or decreasing corticosterone levels through pharmacological supplementation and through surgical removal of the adrenal gland. Here, we utilized the genetically engineered pro-opiomelanocortin (POMC) null mutant mouse, which because of the lack of all POMC peptides has no corticosterone from birth throughout life. The effect of this lifelong absence of corticosterone on the dentate gyrus of the hippocampus is a decrease in granule cell density, which correlated with a decrease in cell proliferation but not an increase in cell degeneration. Fine morphology of granule cells was unaltered. Analyses of gene expression revealed no changes in POMC null mutant vs wild-type hippocampus with respect to levels of expression of corticoid receptor genes or genes known to be regulated by corticosterone. Spatial learning as tested by the Morris water maze was not altered in the POMC null mutant mouse. Taken together with findings from other studies of the effects of altered levels of corticosteroids on the hippocampus, our results argue for a complex homeostasis in which disturbances of any one factor can offset the system in varying ways.
KW - Adrenal
KW - Aldosterone
KW - Corticoid receptor
KW - Dentate gyrus
KW - Glucocorticoids
KW - Hippocampus
KW - Homeostasis
KW - Morris water maze
KW - Pro-opiomelanocortin
UR - http://www.scopus.com/inward/record.url?scp=33646861621&partnerID=8YFLogxK
U2 - 10.1385/JMN:28:3:291
DO - 10.1385/JMN:28:3:291
M3 - Article
C2 - 16691017
AN - SCOPUS:33646861621
VL - 28
SP - 291
EP - 302
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
SN - 0895-8696
IS - 3
ER -