Chronic corticosterone-induced impaired cognitive flexibility is not due to suppressed adult hippocampal neurogenesis

Lui, Erika; Salim, Misbah; Chahal, Manisha; Puri, Nikkita; Marandi, Elahe; Quadrilatero, Joe; Satvat, Elham

doi:10.1016/j.bbr.2017.05.060

Cited by 13 publications

(7 citation statements)

References 103 publications

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“…Importantly, the depressogenic effects of CORT are not restricted to the FST. Rodents subjected to repeated CORT also show impaired cognition, decreased interest in sexual behavior, decreased sucrose preference, decreased home cage activity, and increased immobility in a tail suspension test ( Gorzalka and Hanson, 1998 ; Dwivedi et al, 2015 ; Sturm et al, 2015 ; Huston et al, 2016 ; Lui et al, 2017 ; Brymer et al, 2018 ), without altering nonspecific motor behavior ( Marks et al, 2009 ). However, one should point out that the FST is more a tool to screen antidepressant-like activity that not ascertain depressive-like behavior ( Nestler and Hyman, 2010 ; Molendijk and de Kloet, 2015 ; de Kloet and Molendijk, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Changes in Membrane Protein Clustering in Peripheral Lymphocytes in an Animal Model of Depression Parallel Those Observed in Naïve Depression Patients: Implications for the Development of Novel Biomarkers of Depression

et al. 2018

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Naïve depression patients show alterations in serotonin transporter (SERT) and serotonin 2A (5HT2A) receptor clustering in peripheral lymphocytes, and these alterations have been proposed as a biomarker of therapeutic efficacy in major depression. Repeated corticosterone (CORT) induces a consistent depression-like phenotype and has been widely used as an animal model to study neurobiological alterations underlying the depressive symptoms. In this experiment, we used the CORT paradigm to evaluate whether depression-like behavior is associated with similar changes in the pattern of SERT and 5HT2A membrane protein clustering as those observed in depression patients. We also analyzed the clustering of other proteins expressed in lipid rafts in lymphocytes. Rats received daily CORT or vehicle injections for 21 consecutive days. Afterward they underwent the forced swim test to evaluate depression-like behavior, and isolated lymphocytes were analyzed by immunocytochemistry coupled to image-analysis to study clustering parameters of the SERT, 5HT2A receptor, dopamine transporter (DAT), Beta2 adrenergic receptor (β2AR), NMDA 2B receptor (NR2B), Pannexin 1 (Pnx1), and prion cellular protein (PrPc). Our results showed that CORT increases the size of protein clusters for all proteins with the exception of β 2AR, which is decreased. CORT also increased the number of clusters for Pnx1 and PrPc only. Overall, these results indicate that alterations in SERT and 5HT2A protein clustering in naïve depression patients are paralleled by changes seen in an animal model of depression. The CORT paradigm may be a useful screen for examining additional proteins in lymphocytes as a preliminary step prior to their analysis as biomarkers of depression in human blood samples.

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Section: Discussionmentioning

confidence: 99%

Changes in Membrane Protein Clustering in Peripheral Lymphocytes in an Animal Model of Depression Parallel Those Observed in Naïve Depression Patients: Implications for the Development of Novel Biomarkers of Depression

et al. 2018

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“…The secretion of stress hormones in response to acutely threatening situations is adaptive in the short term (Kaplowitz, Savenkova, Karatsoreos, & Romeo, ; McEwen, ; Meaney & Szyf, ), but chronic exposure to such hormones leads to neural and psychological dysfunction in both adults and adolescents (Belanoff, Gross, Yager, & Schatzberg, ; Duman & Aghajanian, ; Lupien, McEwen, Gunnar, & Heim, ; McEwen, ; Vyas, Mitra, Shankaranarayana Rao, & Chattarji, ). Chronic stressors, either exposure to synthetic glucocorticoids or psychological stressors such as restraint, can impair spatial memory (e.g., tested in maze tasks) in adult animals, and these effects may be mediated by alterations to the hippocampus, which is a particularly stress‐sensitive region of the brain (Luine, Villegas, Martinez, & McEwen, ; Yau et al, ; but see Lui et al, ). These deficits are typically exhibited soon after the stressor exposure has terminated, and are often temporary (i.e., no longer evident after an 18‐day stress‐free period; Luine et al, ).…”

Section: Introductionmentioning

confidence: 99%

Differences in the persistence of spatial memory deficits induced by a chronic stressor in adolescents compared to juveniles

Stylianakis

Harmon-Jones

Richardson

et al. 2018

Developmental Psychobiology

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Adolescence is thought of as a stress-sensitive developmental period. While many studies have compared adolescent responses to stress relative to that of adults, a growing body of work has examined stress responses in juveniles. Here we investigated if a chronic stressor has a differential effect on spatial memory in rats depending on whether it occurs during adolescence or the juvenile period. Male rats were exposed to the stress hormone corticosterone (Cort) in their drinking water, a vehicle control (2.5% ethanol), or water, for 7 days before being tested on a novel Object/Place task 6 days or 6 weeks later. Exposure to Cort or ethanol at either age impaired spatial memory at the 6-day test. The ethanol induced impairment was attenuated 6 weeks later. However, rats given Cort during adolescence, but not the juvenile period, were still impaired. Together, these results suggest that adolescence is indeed a stress-sensitive period.

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“…This assertion was supported by our finding that CORT levels were highly correlated with anxiety-like behavior ( Figure 7A). Studies using experimental models of early stress have also shown that the imbalance of stress hormones can lead to cognitive impairment (50). Adolescence is a period of extensive brain maturation in which synaptic balance and stability are developed and cognitive function and synaptic plasticity are matured (51).…”

Section: Discussionmentioning

confidence: 99%

Effects of BDNF Signaling on Anxiety-Related Behavior and Spatial Memory of Adolescent Rats in Different Length of Maternal Separation

Zhang

Sun

et al. 2020

Front. Psychiatry

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As an adverse form of early-life stress (ELS), maternal separation (MS) can interfere with the development of cognition and behaviors of adolescent rodents. Brain-derived neurotrophic factor (BDNF) is involved in the regulation of brain development and function, but the molecular mechanisms by which BDNF regulates brain function and behavior in MS with different stressor strengths remain unclear. This descriptive study characterized the levels of BDNF in the prefrontal cortex (PFC) and plasma corticosterone (CORT) from the offspring of rats exposed to early handling (EH, 15-min separation per day) and prolonged MS (PMS, 180-min separation per day), during postnatal days (PND) 1-21. The behavioral and biochemical analyses were performed during adolescence (PND 42-56). PMS resulted in reduced weight and decreased locomotor activity in the open field test and Y-maze task compared to control (CON) group, with EH showing an intermediate phenotype. BDNF protein levels in the PFC were lower in PMS compared to EH and further reduced in CON male rats. Plasma CORT levels were higher in PMS compared to CON with EH again showing intermediate levels. Neither PMS or EH affected spatial learning in the Y-maze task. These findings indicate that longer periods of maternal separation are necessary to increase anxiety-like behavior, elevate CORT levels, and further suppress BDNF levels in the PFC, providing a possible mechanism to explain why more severe forms of ELS lead to more significant psychiatric and medical consequences later in life.

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Chronic corticosterone-induced impaired cognitive flexibility is not due to suppressed adult hippocampal neurogenesis

Cited by 13 publications

References 103 publications

Changes in Membrane Protein Clustering in Peripheral Lymphocytes in an Animal Model of Depression Parallel Those Observed in Naïve Depression Patients: Implications for the Development of Novel Biomarkers of Depression

Changes in Membrane Protein Clustering in Peripheral Lymphocytes in an Animal Model of Depression Parallel Those Observed in Naïve Depression Patients: Implications for the Development of Novel Biomarkers of Depression

Differences in the persistence of spatial memory deficits induced by a chronic stressor in adolescents compared to juveniles

Effects of BDNF Signaling on Anxiety-Related Behavior and Spatial Memory of Adolescent Rats in Different Length of Maternal Separation

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