Memory Scores in Middle-Aged Rats Predict Later Deficits in Memory, Paradoxical Sleep, and Blood Glucose Regulation in Old Age

Stone, William S.; Rudd, Rebecca J.; Parsons, Michael; Gold, Paul E.

doi:10.1080/03610739708254285

Cited by 21 publications

(12 citation statements)

References 35 publications

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“…Mild cognitive deficits occur as early as middle-age and are predictive of progressive deficits in humans and in rodents (Larrabee and Crook, 1994;Stone et al, 1997). Visuospatial ability shows a strong association with age, in both humans and in rodent models (Aenlle et al, 2009;Ennaceur et al, 2008;Hoogendam et al, 2014).…”

Section: Discussionmentioning

confidence: 97%

Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice

Abdourahman

Tamm

et al. 2015

Pharmacology Biochemistry and Behavior

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Cognitive decline occurs during healthy aging, even in middle-aged subjects, via mechanisms that could include reduced stem cell proliferation, changed growth factor expression and/or reduced expression of synaptic plasticity genes. Although antidepressants alter these mechanisms in young rodents, their effects in older animals are unclear. In middle-aged mice, we examined the effects of a selective serotonin reuptake inhibitor (fluoxetine) and a multimodal antidepressant (vortioxetine) on cognitive and affective behaviors, brain stem cell proliferation, growth factor and gene expression. Twelve-month-old female C57BL/6 mice exhibited impaired visuospatial memory in the novel object placement (location) task associated with reduced expression of several plasticity-related genes. Chronic treatment with vortioxetine, but not fluoxetine, improved visuospatial memory and reduced depression-like behavior in the forced swim test in middle-aged mice. Vortioxetine, but not fluoxetine, increased hippocampal expression of several neuroplasticity-related genes in middle-aged mice (e.g., Nfkb1, Fos, Fmr1, Camk2a, Arc, Shank1, Nlgn2, and Rab3a). Neither drug reversed the age-associated decrease in stem cell proliferation. Hippocampal growth factor levels were not consistent with behavioral outcomes. Thus, a change in the expression of multiple genes involved in neuronal plasticity by antidepressant treatment was associated with improved cognitive function and a reduction in depression-like behavior in middle-aged mice.

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Section: Discussionmentioning

confidence: 97%

Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice

Abdourahman

Tamm

et al. 2015

Pharmacology Biochemistry and Behavior

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“…Rats were tested in the dark in the T-Maze with no visual cues provided to minimize the influence of cataracts in HIV-1 Tg rats, as done by others [33]. In this regard it should be noted that spontaneous alternation behavior (SAB) has been used in aged rats with visual impairments [34] and to compare anophthalmic mutant mice to wild-type controls [35]. It has been previously shown that HIV transgenic rats exhibit impairment in a spatial reversal learning task [36] without any deficit in spatial memory or motor activity [37].…”

Section: Discussionmentioning

confidence: 99%

Gene expression changes consistent with neuroAIDS and impaired working memory in HIV-1 transgenic rats

Repunte‐Canonigo

Lefèbvre

George

et al. 2014

Mol Neurodegeneration

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BackgroundA thorough investigation of the neurobiology of HIV-induced neuronal dysfunction and its evolving phenotype in the setting of viral suppression has been limited by the lack of validated small animal models to probe the effects of concomitant low level expression of multiple HIV-1 products in disease-relevant cells in the CNS.ResultsWe report the results of gene expression profiling of the hippocampus of HIV-1 Tg rats, a rodent model of HIV infection in which multiple HIV-1 proteins are expressed under the control of the viral LTR promoter in disease-relevant cells including microglia and astrocytes. The Gene Set Enrichment Analysis (GSEA) algorithm was used for pathway analysis. Gene expression changes observed are consistent with astrogliosis and microgliosis and include evidence of inflammation and cell proliferation. Among the genes with increased expression in HIV-1 Tg rats was the interferon stimulated gene 15 (ISG-15), which was previously shown to be increased in the cerebrospinal fluid (CSF) of HIV patients and to correlate with neuropsychological impairment and neuropathology, and prostaglandin D2 (PGD2) synthase (Ptgds), which has been associated with immune activation and the induction of astrogliosis and microgliosis. GSEA-based pathway analysis highlighted a broad dysregulation of genes involved in neuronal trophism and neurodegenerative disorders. Among the latter are genesets associated with Huntington’s disease, Parkinson’s disease, mitochondrial, peroxisome function, and synaptic trophism and plasticity, such as IGF, ErbB and netrin signaling and the PI3K signal transduction pathway, a mediator of neural plasticity and of a vast array of trophic signals. Additionally, gene expression analyses also show altered lipid metabolism and peroxisomes dysfunction. Supporting the functional significance of these gene expression alterations, HIV-1 Tg rats showed working memory impairments in spontaneous alternation behavior in the T-Maze, a paradigm sensitive to prefrontal cortex and hippocampal function.ConclusionsAltogether, differentially regulated genes and pathway analysis identify specific pathways that can be targeted therapeutically to increase trophic support, e.g. IGF, ErbB and netrin signaling, and reduce neuroinflammation, e.g. PGD2 synthesis, which may be beneficial in the treatment of chronic forms of HIV-associated neurocognitive disorders in the setting of viral suppression.

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“…The crucial, unanswered question here is whether the reduction in REM and the development of dementia are both epiphenomenal to other mechanisms such as decreased cholinergic neurotransmission (cf. Stone, Rudd, Parsons, & Gold, 1997; Yaffe et al, 2007) or if loss of REM sleep drives cognitive changes (via, e.g., reduced long term potentiation).…”

Section: Polysomnography and Neuropsychological Testingmentioning

confidence: 99%

Sleep, Cognition, and Normal Aging

Scullin

Bliwise

2015

Perspect Psychol Sci

385

155

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Sleep is implicated in cognitive functioning in young adults. With increasing age there are substantial changes to sleep quantity and quality including changes to slow wave sleep, spindle density, and sleep continuity/fragmentation. A provocative question for the field of cognitive aging is whether such changes in sleep physiology affect cognition (e.g., memory consolidation). We review nearly a half-century of research studies across 7 diverse correlational and experimental literature domains, which historically have had little crosstalk. Broadly speaking, sleep and cognitive functions are often related in advancing age, though the prevalence of null effects (including correlations in the unexpected, negative direction) in healthy older adults indicates that age may be an effect modifier of these associations. We interpret the literature as suggesting that maintaining good sleep quality, at least in young adulthood and middle age, promotes better cognitive functioning and serves to protect against age-related cognitive declines.

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Memory Scores in Middle-Aged Rats Predict Later Deficits in Memory, Paradoxical Sleep, and Blood Glucose Regulation in Old Age

Cited by 21 publications

References 35 publications

Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice

Reversal of age-associated cognitive deficits is accompanied by increased plasticity-related gene expression after chronic antidepressant administration in middle-aged mice

Gene expression changes consistent with neuroAIDS and impaired working memory in HIV-1 transgenic rats

Sleep, Cognition, and Normal Aging

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