Endogenous Glucocorticoids Are Essential for Maintaining Prefrontal Cortical Cognitive Function

Mizoguchi, Kazuo; Ishige, Atsushi; Takeda, Susumu; Aburada, Masaki; Tabira, Takeshi

doi:10.1523/jneurosci.0086-04.2004

Cited by 174 publications

(104 citation statements)

References 53 publications

(77 reference statements)

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“…Although the extent to which these hormonal changes are responsible for the structural and functional changes we observed in our obese rats remains unknown, some evidence suggests a causal link. For example, reduced glucocorticoid levels have been associated with diminished dendritic spine density in the PFC (38) and impaired performance on PFC-dependent cognitive tasks (39). The relative protection of the hippocampus during early stage obesity may be due to the temporary ability of elevated circulating leptin levels to compensate for reduced glucocorticoid levels.…”

Section: Discussionmentioning

confidence: 99%

Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function

Bocarsly

Fasolino

Kane

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

210

151

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Obesity is a major public health problem affecting overall physical and emotional well-being. Despite compelling data suggesting an association between obesity and cognitive dysfunction, this phenomenon has received relatively little attention. Neuroimaging studies in obese humans report reduced size of brain regions involved in cognition, but few studies have investigated the cellular processes underlying cognitive decline in obesity or the influence of obesity on cognition in the absence of obesity-related illnesses. Here, a rat model of diet-induced obesity was used to explore changes in brain regions important for cognition. Obese rats showed deficits on cognitive tasks requiring the prefrontal and perirhinal cortex. Cognitive deficits were accompanied by decreased dendritic spine density and synaptic marker expression in both brain regions. Microglial morphology was also changed in the prefrontal cortex. Detrimental changes in the prefrontal cortex and perirhinal cortex occurred before metabolic syndrome or diabetes, suggesting that these brain regions may be particularly vulnerable to early stage obesity.O besity is a growing public health concern, affecting more than one-third of the United States adult population (1). Obesity increases the incidence of diabetes, vascular disease, and mental illness, all of which reduce quality of life and place a heavy financial burden on patients and society. Less recognized consequences of obesity are its deleterious effects on cognitive function. Individual cognitive performance, both rudimentary and scholastic, declines with increases in body mass and energy consumption (2-5). These deficits can be observed throughout life, from childhood to late adulthood. Obesity is also associated with an increased incidence of mild cognitive impairment and dementia in the elderly (6).Some evidence suggests that obese individuals have decreased overall brain volume (7), with further studies indicating more specific reductions in the volume of brain regions important for cognition, including the hippocampus, prefrontal cortex (PFC), and anterior cingulate (5,8,9). Few studies, however, have investigated the cellular and biochemical mechanisms that might underlie obesityinduced changes in brain volume and cognitive function.Although clinical studies strongly suggest that obesity produces cognitive impairment and brain atrophy, it is difficult to determine whether these changes arise from obesity itself or from conditions often associated with obesity, like metabolic syndrome, diabetes, and vascular disease. Such conditions, even in the absence of obesity, have been linked to cognitive dysfunction and decreases in brain volume (10-13). Little research has been done exploring the effects of obesity on brain structure and cognition in obese, but otherwise healthy, individuals. To investigate whether obesity in the absence of obvious illness alters brain structure and function, we used a rat model of dietinduced obesity to assess the PFC, the perirhinal cortex (PRC), and the hippocampus...

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Section: Discussionmentioning

confidence: 99%

Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function

Bocarsly

Fasolino

Kane

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

210

151

View full text Add to dashboard Cite

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“…This indicates that the rhythm of CORT not only increases spines but also supports the survival of newly formed spines. Other studies showed that the spatial memory (which is hippocampal dependent) and working memory (which is prefrontal cortex dependent) were impaired by ADX (Conrad et al 1997, Mizoguchi et al 2004. Furthermore, ADX rats show depression-like behavior in the rotarod test (Mizoguchi et al 2008).…”

Section: Concentration-dependent Functions Of Non-stress Level Of Cormentioning

confidence: 96%

Hippocampal spine changes across the sleep–wake cycle: corticosterone and kinases

Ikeda¹,

Hojo²,

Komatsuzaki³

et al. 2015

Journal of Endocrinology

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The corticosterone (CORT) level changes along the circadian rhythm. Hippocampus is sensitive to CORT, since glucocorticoid receptors are highly expressed. In rat hippocampus fixed in a living state every 3 h, we found that the dendritic spine density of CA1 pyramidal neurons increased upon waking (within 3 h), as compared with the spine density in the sleep state. Particularly, the large-head spines increased. The observed change in the spine density may be due to the change in the hippocampal CORT level, since the CORT level at awake state (w30 nM) in cerebrospinal fluid was higher than that at sleep state (w3 nM), as observed from our earlier study. In adrenalectomized (ADX) rats, such a wake-induced increase of the spine density disappeared. S.c. administration of CORT into ADX rats rescued the decreased spine density. By using isolated hippocampal slices, we found that the application of 30 nM CORT increased the spine density within 1 h and that the spine increase was mediated via PKA, PKC, ERK MAPK, and LIMK signaling pathways. These findings suggest that the moderately rapid increase of the spine density on waking might mainly be caused by the CORT-driven kinase networks.

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“…These differences seem not to depend on the intensity of the stress protocol since similar results were also obtained using handling, a milder stress challenge (Segovia et al 2008a,b). Since different studies have shown that corticosterone can modulate dopamine levels in the PFC (Imperato et al 1989;Mizoguchi et al 2004;Ago et al 2009), it is possible that the reduced increases of dopamine are secondary to the lower increases of corticosterone observed in the PFC of the EC rats. This would be in agreement with the reduction of stress-evoked dopamine release after blockade of GRs locally within PFC (Butts et al 2011).…”

Section: Acute Stress Dopamine and Acetylcholine In The Pfcmentioning

confidence: 99%

Differential effects of environmental enrichment and isolation housing on the hormonal and neurochemical responses to stress in the prefrontal cortex of the adult rat: relationship to working and emotional memories

et al. 2012

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The present study was designed to investigate the modulation of the stress responses by the environmental conditions and its putative neurobiological mechanisms. For that an integrative study on the effects of environmental enrichment and isolation housing on 1/ the corticosterone, dopamine and acetylcholine responses to acute restraint stress in the prefrontal cortex (PFC) of the awake rat; 2/ the mRNA levels of glucocorticoid receptors (GRs) in the PFC; and 3/ the behavioral responses to stress, related to the PFC (habituation to a novel environment, spatial-working memory and inhibitory avoidance response) was performed. Male Wistar rats were maintained from 3 to 6 months of age in two different conditions: enriched (EC) or impoverished (IC). Animals were stereotaxically implanted with bilateral guide cannulae in the PFC to perform microdialysis experiments to evaluate the concentrations of corticosterone, dopamine and acetylcholine. EC animals showed lower increases of corticosterone and dopamine but not of acetylcholine than IC animals in the PFC in response to acute restraint stress (20min). In the PFC, GR mRNA levels showed a trend towards an enhancement in EC animals. EC reduced the days to learn the spatial working memory task (radial-water maze). Spatial working memory, however, was not different between groups in either basal or stress conditions. Inhibitory avoidance response was reduced in EC rats. The changes produced by EC in the neurochemical, neuroendocrine and behavioral parameters evaluated suggest that EC rats could show a better coping during an acute stress challenge.

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Endogenous Glucocorticoids Are Essential for Maintaining Prefrontal Cortical Cognitive Function

Cited by 174 publications

References 53 publications

Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function

Obesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function

Hippocampal spine changes across the sleep–wake cycle: corticosterone and kinases

Differential effects of environmental enrichment and isolation housing on the hormonal and neurochemical responses to stress in the prefrontal cortex of the adult rat: relationship to working and emotional memories

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