| Title: |
Neuroprotection provided by dietary restriction in rats is further enhanced by reducing glucocortocoids |
| Authors: |
Qiu, G; Spangler, EL; Wan, RQ; Miller, M; Mattson, MP; So, KF; Cabo, R; Zou, S; Ingram, DK |
| Publisher Information: |
//www.elsevier.com/locate/neuaging; United States |
| Publication Year: |
2012 |
| Collection: |
University of Hong Kong: HKU Scholars Hub |
| Subject Terms: |
Brain-Derived Neurotrophic Factor - analysis; Caloric Restriction; Corticosterone - blood - deficiency; Hippocampus - cytology - drug effects; Memory Disorders - chemically induced - diet therapy |
| Description: |
Glucocorticoids (GC)--corticosterone (CORT) in rodents and cortisol in primates--are stress-induced hormones secreted by adrenal glands that interact with the hypothalamic pituitary axis. High levels of cortisol in humans are observed in neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), as well as in diabetes, post-traumatic stress syndrome, and major depression. Experimental models of diabetes in rats and mice have demonstrated that reduction of CORT reduces learning and memory deficits and attenuates loss of neuronal viability and plasticity. In contrast to the negative associations of elevated GC levels, CORT is moderately elevated in dietary restriction (DR) paradigms which are associated with many healthy anti-aging effects including neuroprotection. We demonstrate here in rats that ablating CORT by adrenalectomy (ADX) with replenishment to relatively low levels (30% below that of controls) prior to the onset of a DR regimen (ADX-DR) followed by central administration of the neurotoxin, kainic acid (KA), significantly attenuates learning deficits in a 14-unit T-maze task. The performance of the ADX-DR KA group did not differ from a control group (CON) that did not receive KA and was fed ad libitum (AL). By contrast, the sham-operated DR (SHAM-DR KA) group, SHAM-AL KA group, and ADX-AL KA group demonstrated poorer learning behavior in this task compared to the CON group. Stereological analysis revealed equivalent DR-induced neuroprotection in the SH-DR KA and ADX-DR KA groups, as measured by cell loss in the CA2/CA3 region of the hippocampus, while substantial cell loss was observed in SH-AL and ADX-AL rats. A separate set of experiments was conducted with similar dietary and surgical treatment conditions but without KA administration to examine markers of neurotrophic activity, brain-derived neurotrophic factor (BDNF), transcriptions factors (pCREB), and chaperone proteins (HSP-70). Under these conditions, we noted elevations in both BDNF and pCREB in ADX DR rats ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Neurobiology of Aging; Neurobiology of Aging, 2012, v. 33 n. 10, p. 2398–2410; 2398–2410; 213062; WOS:000308088500016; 10; PMC3374050; https://hub.hku.hk/handle/10722/180133; 33 |
| DOI: |
10.1016/j.neurobiolaging.2011.11.025 |
| Availability: |
https://hub.hku.hk/handle/10722/180133; https://doi.org/10.1016/j.neurobiolaging.2011.11.025; http://library.hku.hk:4550/resserv?sid=HKU:IR&issn=2398-2410&volume=33&spage=&epage=&date=2011&atitle=Neuroprotection+provided+by+dietary+restriction+in+rats+is+further+enhanced+by+reducing+glucocortocoids |
| Accession Number: |
edsbas.C6283D41 |
| Database: |
BASE |