Mechanisms of Late-Onset Cognitive Decline after Early-Life Stress

Brunson, Kristen L.; Kramár, Enikö A.; Lin, Bin; Chen, Yuncai; Colgin, Laura Lee; Yanagihara, Theodore K.; Lynch, Gary; Baram, Tallie Z.

doi:10.1523/jneurosci.2281-05.2005

Cited by 414 publications

(520 citation statements)

References 78 publications

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“…Nevertheless, the rat does not show the gross changes in white matter that humans undergo with age. On a speculative note, it is possible that the controlled experiences of laboratory rats have eliminated two critical factors that have been shown to impact aging: stress and immune challenges across the lifespan (Lupien et al, 1998;Brunson et al, 2005;Sandi & Touyarot, 2006;Montaron et al, 2006;Godbout & Johnson, 2006). Why the corpus callosum of the laboratory rat does not age as readily as the human may be worth exploring to better understand the course of human aging.…”

Section: Discussionmentioning

confidence: 99%

Increases in size and myelination of the rat corpus callosum during adulthood are maintained into old age

Yates

Juraska

2007

Brain Research

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Although there are indications of growth in the size and myelination of the rat corpus callosum during adulthood, it is not known how long this growth continues. In addition, the potential for age-related changes in these measures to affect the sex differences seen in adulthood has not been examined. Here the size of callosal subregions and area occupied by myelin were examined in the genu and splenium of male and female rats in adulthood, middle-age, and old age. Our findings revealed increases both in size and in the area composed of myelin between adulthood and middle-age that were maintained into old age, with no indications of age-related loss in either the genu or splenium of the rat.

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Section: Discussionmentioning

confidence: 99%

Increases in size and myelination of the rat corpus callosum during adulthood are maintained into old age

Yates

Juraska

2007

Brain Research

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“…Electrophysiological studies suggest that stress alters synaptic plasticity in both CA3 and CA1, but the responsible mechanisms are extremely complex and involve pre-and postsynaptic elements in both regions. 22,30,70 The absence of Fos activation in CA3 in adult neurons is particularly notable, and it is tempting to speculate that this might be a neuroprotective mechanism: Stress 35 as well as large doses of CRH may injure and kill hippocampal CA3 neurons in developing hippocampus. 49,85 The absence of this activation in the adult might prevent hyperexcitability and excitotoxicity of this neuronal population.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, longer psychological stress during the first/second week of life has been shown to abolish long-term potentiation and provoke impaired learning and memory during middle age. 22 This was associated with altered expression of several hippocampal genes, including the gene for CRH itself (Brunson et al 56 and unpublished data). Remarkably, the CRH gene is regulated by CREB, via a CRE in its promoter.…”

Section: Discussionmentioning

confidence: 99%

“…13,14 Finally, during aging, stress-evoked glucocorticoids may provoke more profound loss or dysfunction of neurons. [15][16][17][18][19] Focusing on the effects of stress on the hippocampal formation, age-dependent consequences of 'psychological' stress may be governed by the maturity of stress-responsive hippocampal circuits [20][21][22] as well as by other undefined age-specific vulnerabilities. In addition, the age-related differential effects of stress on hippocampal neurons may be attributable to the fact that stressful signals reach and influence different neuronal populations in immature and adult brain.…”

Section: Introductionmentioning

confidence: 99%

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Cellular and molecular mechanisms of hippocampal activation by acute stress are age-dependent

et al. 2006

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The effects of stress, including their putative contribution to pathological psychiatric conditions, are crucially governed by the age at which the stress takes place. However, the cellular and molecular foundations for the impact of stress on neuronal function, and their change with age, are unknown. For example, it is not known whether 'psychological' stress signals are perceived by similar neuronal populations at different ages, and whether they activate similar or age-specific signaling pathways that might then mediate the spectrum of stress-evoked neuronal changes. We employed restraint and restraint/noise stress to address these issues in juvenile (postnatal day 18, [P18]) and adult rats, and used phosphorylation of the transcription factor CREB (pCREB) and induction of c-fos as markers of hippocampal neuronal responses. Stress-activated neuronal populations were identified both anatomically and biochemically, and selective blockers of the stress-activated hippocampal peptide, corticotropin-releasing hormone (CRH) were used to probe the role of this molecule in stressinduced hippocampal cell activation. Stress evoked strikingly different neuronal response patterns in immature vs adult hippocampus. Expression of pCREB appeared within minutes in hippocampal CA3 pyramidal cells of P18 rats, followed by delayed induction of Fos protein in the same cell population. In contrast, basal pCREB levels were high in adult hippocampus and were not altered at 10-120 min by stress. Whereas Fos induction was elicited by stress in the adult, it was essentially confined to area CA1, with little induction in CA3. At both age groups, central pretreatment with either a nonselective blocker of CRH receptors or the CRF 1 -selective antagonist, NBI 30775, abolished stress-evoked neuronal activation. In conclusion, hippocampal neuronal responses to psychological stress are generally more rapid and robust in juvenile rats, compared to fully mature adults, and at both ages, CRH plays a key role in this process. Enhanced hippocampal response to stress during development, and particularly the activation of the transcription factor CREB, may contribute to the enduring effects of stress during this period on hippocampal function.

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“…Studies in rats reveal that surges of corticosteroids during critical developmental periods produce long-term impairments during postnatal life (Avishai-Eliner et al, 2002;Brunson et al, 2005;Matthews, 2000;. Several different techniques were used and invariably caused detrimental effects on the offspring.…”

Section: Introductionmentioning

confidence: 99%

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

Velı́šek

2006

Neuropsychopharmacol

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Repeated antenatal administration of betamethasone is frequently used as a life-saving treatment in obstetrics. However, limited information is available about the outcome of this therapy in children. The initial prospective studies indicate that there are behavioral impairments in children exposed to repeated courses of prenatal betamethasone during the third trimester of pregnancy. In this study, pregnant rats received two betamethasone injections on day 15 of gestation. Using immunohistochemistry, the expression of a powerful anxiolytic molecule neuropeptide Y (NPY) was determined on postnatal day (PN) 20 in the hippocampus and basolateral amygdala (structures related to anxiety and fear) of the offspring. Prenatal betamethasone exposure induced significant increases in NPY expression in the hippocampus but not in the amygdala. Indeed, behavioral tests in the offspring, between PN20 and PN22 in the open field, on the horizontal bar, and in the elevated plus maze, indicated decreases in anxiety, without impairments in motor performance or total activity. Decreased body weight in betamethasone-exposed rats confirmed long-lasting effects of prenatal exposure. Thus, prenatal betamethasone treatment consistently increases hippocampal NPY, with decreases in anxiety-related behaviors and hippocampal role in anxiety in rats. Animal models may assist in differentiation between pathways of the desired main effect of the antenatal corticosteroid treatment and pathways of unwanted side effects. This differentiation can lead to specific therapeutic interventions directed against the side effects without eliminating the beneficial main effect of the corticosteroid treatment.

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Mechanisms of Late-Onset Cognitive Decline after Early-Life Stress

Cited by 414 publications

References 78 publications

Increases in size and myelination of the rat corpus callosum during adulthood are maintained into old age

Increases in size and myelination of the rat corpus callosum during adulthood are maintained into old age

Cellular and molecular mechanisms of hippocampal activation by acute stress are age-dependent

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

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