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Cited by 250Stress Responses and CortisolMemory and Neural MechanismsNeuroendocrine regulation and behavior

Postnatal handling attenuates certain neuroendocrine, anatomical, and cognitive dysfunctions associated with aging in female rats

Meaney, Michael J., Aitken, David H., Bhatnagar, Seema, Sapolsky, Robert M.·1991·Neurobiology of Aging
DOI 10.1016/0197-4580(91)90036-j
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Abstract

Hippocampal degeneration with aging is associated with increased hypothalamic-pituitary-adrenal (HPA) activity and, in male rats, both are attenuated by postnatal handling. Considering the important sex differences in the effects of handling and in HPA responses to stress in older rats, we have examined the effects of postnatal handling on aging in females. Female, Long-Evans rats were handled (H) during the first 3 weeks of life and later compared with nonhandled (NH) controls at various ages. Handling resulted in permanently increased hippocampal type II, glucocorticoid receptor binding. Relative to H females, NH females showed increased basal corticosterone levels in later life and hypersecreted corticosterone following stress at all ages examined. Both effects are similar to those reported in males. However, unlike males, H and NH females did not differ in corticosterone levels achieved during stress, a finding that may be related to sex-dependent effects of handling on pituitary transcortin receptors. There were no differences in hippocampal neuron density in 6-month-old animals. However, the older NH animals showed considerable neuron loss in the CA1 and CA3 hippocampal cellfields. There was little or no neuron loss in the H animals. Finally, the NH animals exhibited age-related spatial memory impairments, such that by 24 months of age the performance of the NH females was profoundly worse than that of the younger NHs and same-aged H animals. These data suggest that early handling permanently alters CNS systems that regulate hypothalamic-pituitary-adrenal (HPA) function, although the effect may depend on the gender of the animal. In both males and females, however, handling appears to prevent (or minimize) increased adrenal secretion in later life and to attenuate hippocampal cell loss and spatial memory impairments.

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  • Rodent studies show brain morphology changes after manipulation of the early postnatal environment.

    “Therefore, it is interesting to note that there is an impressive body of evidence from rodent studies showing changes in brain morphology in association with manipulation of the early postnatal environment (e.g. Meaney et al., 1991; Pham et al., 1999; Helmeke et al., 2001; Huot et al., 2002; Roceri et al., 2002; Bredy et al., 2003; Ovtscharoff et al., 2006; Fabricius et al., 2008).”

    From High pregnancy anxiety during mid-gestation is associated with decreased gray matter density in 6-9-year-old children. (2010) · cites this paper as Meaney et al., 1991

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Authors
Meaney, M. J., Aitken, D. H., Bhatnagar, S., & Sapolsky, R. M.
Affiliations
  • Douglas Mental Health University Institute (CA)
  • Stanford University (US)
Corresponding author
Meaney, Michael J.
ORCID
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
1991-01
Volume
12
Issue
1
Pages
31-38
ISSN
0197-4580 (ISSN-L)
DOI
10.1016/0197-4580(91)90036-j
OpenAlex
W2036587591
Cited by
250
References
72
Citations by year
2026: 1 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 8 · 2013: 3 · 2012: 10
FWCI
6.11
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ag006633-08)
  • National Institute on Aging (AG-06633)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords
postnatal handling, aging, female rats, hippocampal neurodegeneration, hypothalamic-pituitary-adrenal axis, glucocorticoid receptor binding, corticosterone, stress response, sex differences, hippocampal neuronal loss, CA1 and CA3, spatial memory impairment, neuroendocrine dysfunction
MeSH terms
Aging, Analysis of Variance, Animals, Animals, Newborn, Cell Count, Cognition, Corticosterone, Female, Handling, Psychological, Hippocampus, Memory, Neurons, Rats, Inbred Strains, Receptors, Glucocorticoid, Receptors, Steroid, Restraint, Physical, Rats

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