Abstract
Early-life experience, including maternal care, influences hippocampus-dependent learning and memory throughout life. Handling of pups during postnatal days (P)2-9 stimulates maternal care and leads to improved memory function and stress-coping. The underlying molecular mechanisms may involve early (by P9) and enduring reduction of hypothalamic corticotropin-releasing factor (CRF) expression and subsequent (by P45) increase of hippocampal glucocorticoid receptor (GR) expression. However, whether hypothalamic CRF levels influence changes in hippocampal GR expression (and memory function), via reduced CRF-receptor activation and consequent lower plasma glucocorticoid levels, is unclear. Here, we administered selective antagonist for the type-1 CRF receptor, NBI 30775, to nonhandled rats post hoc from P10 to P17 and examined hippocampus-dependent learning and memory later (on P50-P70) using two independent paradigms, compared with naive & vehicle-treated nonhandled, and naive and antagonist-treated handled rats. Hippocampal GR and hypothalamic CRF mRNA levels and stress-induced plasma corticosterone levels were also examined. Transient, partial selective blockade of CRF1 in nonhandled rats improved memory functions on both the Morris watermaze and object recognition tests to levels significantly better than naive and vehicle-treated controls, and were indistinguishable from those of handled (naive, vehicle- and antagonist-treated) rats. GR mRNA expression was increased in hippocampal CA1 and the dentate gyrus of CRF1- antagonist treated nonhandled rats to levels commensurate with those of handled cohorts. Thus, the extent of CRF1 activation, likely involving changes of hypothalamic CRF levels and release, contributes to the changes in hippocampal GR expression and learning and memory function.
| Original language | English |
|---|---|
| Pages (from-to) | 4090-4096 |
| Number of pages | 7 |
| Journal | Endocrinology |
| Volume | 146 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 2005 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Endocrinology
- Endocrinology, Diabetes and Metabolism
Cite this
Enduring, handling-evoked enhancement of hippocampal memory function and GR expression involves activation of the CRF type-1 receptor. / Simeone, Kristina A.; Brunson, Kristen L.; Avishai-Eliner, Sarit; Stone, Blake A.; Kapadia, Bhumika J.; Baram, Tallie Z.
In: Endocrinology, Vol. 146, No. 9, 09.2005, p. 4090-4096.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enduring, handling-evoked enhancement of hippocampal memory function and GR expression involves activation of the CRF type-1 receptor
AU - Simeone, Kristina A.
AU - Brunson, Kristen L.
AU - Avishai-Eliner, Sarit
AU - Stone, Blake A.
AU - Kapadia, Bhumika J.
AU - Baram, Tallie Z.
PY - 2005/9
Y1 - 2005/9
N2 - Early-life experience, including maternal care, influences hippocampus-dependent learning and memory throughout life. Handling of pups during postnatal days (P)2-9 stimulates maternal care and leads to improved memory function and stress-coping. The underlying molecular mechanisms may involve early (by P9) and enduring reduction of hypothalamic corticotropin-releasing factor (CRF) expression and subsequent (by P45) increase of hippocampal glucocorticoid receptor (GR) expression. However, whether hypothalamic CRF levels influence changes in hippocampal GR expression (and memory function), via reduced CRF-receptor activation and consequent lower plasma glucocorticoid levels, is unclear. Here, we administered selective antagonist for the type-1 CRF receptor, NBI 30775, to nonhandled rats post hoc from P10 to P17 and examined hippocampus-dependent learning and memory later (on P50-P70) using two independent paradigms, compared with naive & vehicle-treated nonhandled, and naive and antagonist-treated handled rats. Hippocampal GR and hypothalamic CRF mRNA levels and stress-induced plasma corticosterone levels were also examined. Transient, partial selective blockade of CRF1 in nonhandled rats improved memory functions on both the Morris watermaze and object recognition tests to levels significantly better than naive and vehicle-treated controls, and were indistinguishable from those of handled (naive, vehicle- and antagonist-treated) rats. GR mRNA expression was increased in hippocampal CA1 and the dentate gyrus of CRF1- antagonist treated nonhandled rats to levels commensurate with those of handled cohorts. Thus, the extent of CRF1 activation, likely involving changes of hypothalamic CRF levels and release, contributes to the changes in hippocampal GR expression and learning and memory function.
AB - Early-life experience, including maternal care, influences hippocampus-dependent learning and memory throughout life. Handling of pups during postnatal days (P)2-9 stimulates maternal care and leads to improved memory function and stress-coping. The underlying molecular mechanisms may involve early (by P9) and enduring reduction of hypothalamic corticotropin-releasing factor (CRF) expression and subsequent (by P45) increase of hippocampal glucocorticoid receptor (GR) expression. However, whether hypothalamic CRF levels influence changes in hippocampal GR expression (and memory function), via reduced CRF-receptor activation and consequent lower plasma glucocorticoid levels, is unclear. Here, we administered selective antagonist for the type-1 CRF receptor, NBI 30775, to nonhandled rats post hoc from P10 to P17 and examined hippocampus-dependent learning and memory later (on P50-P70) using two independent paradigms, compared with naive & vehicle-treated nonhandled, and naive and antagonist-treated handled rats. Hippocampal GR and hypothalamic CRF mRNA levels and stress-induced plasma corticosterone levels were also examined. Transient, partial selective blockade of CRF1 in nonhandled rats improved memory functions on both the Morris watermaze and object recognition tests to levels significantly better than naive and vehicle-treated controls, and were indistinguishable from those of handled (naive, vehicle- and antagonist-treated) rats. GR mRNA expression was increased in hippocampal CA1 and the dentate gyrus of CRF1- antagonist treated nonhandled rats to levels commensurate with those of handled cohorts. Thus, the extent of CRF1 activation, likely involving changes of hypothalamic CRF levels and release, contributes to the changes in hippocampal GR expression and learning and memory function.
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U2 - 10.1210/en.2004-1285
DO - 10.1210/en.2004-1285
M3 - Article
VL - 146
SP - 4090
EP - 4096
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 9
ER -