Delivery method matters: omega-3 supplementation by restricted feeding period and oral gavage has a distinct impact on corticosterone secretion and anxious behavior in adolescent rats.

Objectives: Oral gavage and time-restricted feeding are common delivery methods for dietary supplementation to rodents. However, the stress associated with selected feeding regimens could represent a confounding variable. In rodents, the adolescence period is particularly vulnerable to stressful events, in part related to ongoing maturation of the brain. In this context, omega-3 dietary supplementation has shown beneficial effects on neuronal growth, cognitive performance and stress regulation, while high-fat diet (HVF) has been associated with enhanced stress and anxiety. Therefore, this study has two aims: (1) evaluate the influence of 21-day supplementation with soybean oil (control group; CSO), fish oil (FO) or hydrogenated vegetable fat (HVF) fatty acids (FA) during the adolescence period on corticosterone secretion and anxiety-like behavior and, (2) compare the impact of dietary supplementation using oral gavage or time-limited feeding on these measures.Methods: Oral gavage or restricted feeding were used to daily feed adolescent rats (PND28-47; n = 49). On supplementation days 1, 7, 14 and 21, droplets of blood were collected for corticosterone (CORT) assessments. The Open Field (OFT) and the Elevated-Plus Maze (EPM) tests served to assess anxiety-like behavior on PND50.Results: Our findings indicate increased CORT secretion in restricted-(R) compared to gavage-fed animals on DAY7 and DAY14, suggesting heightened HPA-axis reactivity. Notably, CORT secretion diminished in FO-R-rats (DAY21), suggesting improved coping/adjustment. Consistent with CORT assessments, findings in the OFT and EPM supported attenuated anxiety in gavage versus restricted groups. FO and CSO supplementation reduced anxiety compared to HVF intake.Conclusions: Our findings uncover a significant impact of feeding methods on anxiety-like behavior and physiological stress response in rodents, supporting oral gavage as a less stressful option during the adolescent developmental stage. Supplement-specific effects on CORT secretion further indicated an influence of fish oil in regulating the stress response.

Sex-specific differences in adult cognition and neuroplasticity following repeated combinatory stress and TrkB receptor antagonism in adolescence.

Evidence supports brain-derived neurotrophic factor (BDNF) and its primary receptor tyrosine-related kinase B (TrkB) as targets in the treatment of mood disorders. This study characterized the impact of a 10-day combinatory stress paradigm (alternating days of restraint stress and forced swim) and administration of the selective TrkB antagonist ANA-12 (0.5 mg/kg, i.p.) during adolescence in male and female Wistar rats on adulthood behavioral and neurochemical responses. The social interaction/preference (SIT/SP), and Y maze conditioned place preference (YMCPP) and passive avoidance tests (YMPAT), initiated on PND 62, served to determine sex-related behavioral responses. Results support reduced sociability in females in the SIT/SP, but no impact of ANA-12 to regulate sociability or social memory. Blockade of TrkB during adolescence facilitated YMCPP-related reward behavior in both sexes, and reduced YMPAT fear conditioning in females. Following behavioral testing, rats were exposed to 5-min acute forced swim and brains collected 2 h post swim to determine effects of adolescent TrkB blockade and stress exposure on neurochemical regulators of stress and plasticity. Findings show elevated glucocorticoid receptor (GR-) and TrkB-immunoreactivity (ir) in the amygdalar central nucleus, and GR-ir in the hypothalamic paraventricular nucleus of females compared to males. In the hippocampal CA1, BDNF-ir was lower in females versus males, and GR-ir was elevated in stress versus non-stress males. Together, we demonstrate that inherent sex-specific differences, which may modulate impact of adolescence stress exposure and TrkB inhibition, differentially affect male and female adulthood behavior and biochemical response profiles, suggesting that these responses are in part conditioned by prior experience.

Blockade of TrkB receptors in the nucleus accumbens prior to heterotypic stress alters corticotropin-releasing hormone (CRH), vesicular glutamate transporter 2 (vGluT2) and glucocorticoid receptor (GR) within the mesolimbic pathway.

Inhibition of stress-induced elevations in brain-derived neurotrophic factor (BDNF) or its primary receptor tyrosine-related kinase B (TrkB) within the reward pathway may modulate vulnerability to anxiety and mood disorders. The current study examined the role of BDNF/TrkB signaling on biochemistry and behavior under basal conditions and following exposure to a 10-day heterotypic stress paradigm in male rats. Effects of intra-accumbal administration of TrkB antagonist ANA-12 (0.25µg/0.5µl/min) on anxiety, and expression of Trk-B, corticotropin-releasing hormone (CRH), vesicular glutamate transporter 2 (vGluT2) and glucocorticoid receptor (GR) within the mesolimbic pathway were determined. Notably, ANA-12 attenuated anxiety-like behavior in stress rats while increasing anxiety in the non-stress group in the elevated plus maze (EPM). At the neurochemical level, ANA-12 blocked the increased vGluT2 and CRH expressions in the hypothalamic PVN and basolateral amygdala in stress rats, while it enhanced vGluT2 and CRH expressions in non-stress rats. ANA-12 also showed state-dependent effects at the NAc core, attenuating TrkB-ir in non-stress rats while reversing reduced expression in stressed rats. At the cingulate cortex, ANA-12 normalized stress-induced increase in TrkB expression. Notably, ANA-12 showed region-specific effects on GR-ir at the NAc core and shell, with increased GR-ir in non-stress rats, although the drug attenuated stress-induced GR-ir expression only in the core portion of the NAc, while having no impact at the cingulate cortex. Elevated blood CORT levels post-stress was not influenced by ANA-12 treatment. Together, these findings suggest that BDNF-mediated TrkB activation exerts differential impact in regulating emotional response under basal and stress conditions.

Dose-related effects of chronic resveratrol administration on neurogenesis, angiogenesis, and corticosterone secretion are associated with improved spatial memory retention following global cerebral ischemia.

OBJECTIVES: The polyphenol resveratrol has shown regulatory effects on hippocampal neurogenesis, which according to the neurovascular niche hypothesis, is likely to involve stimulation of angiogenesis. In rodents, global cerebral ischemia leads to selective CA1 neuronal damage, spatial memory impairments, lasting changes in corticosterone (CORT) secretion, and increased neurogenesis. This study examined dose-related effects of 21-day RSV treatment on markers associated with neurogenesis (DCX, PSA-NCAM) and angiogenesis (CD31) in the hippocampus at short (7-day) and long-term (85-day) intervals following global ischemia. In parallel, post-ischemic and stress-induced CORT levels and spatial memory in the Morris water maze were determined. METHODS: Five groups of male Wistar rats were included: sham/saline, ischemia/saline, ischemia/1 mg/kg RSV, ischemia/10 mg/kg RSV, and sham/10 mg/kg RSV. Changes in expression of plasticity markers were paralleled by assessment of basal- and stress-induced CORT secretions, and spatial memory performance. RESULTS: Our findings revealed a significant attenuation of ischemia-induced DCX/PSA-NCAM expression in RSV-treated rats, whereas RSV treatment increased angiogenesis in the injured CA1 region. RSV attenuated CORT levels 3 days post-ischemia and a trend toward attenuating CORT secretion in response to 15 minutes restraint stress. Increased swimming latencies in the target quadrant during the MWM probe trial in RSV-treated ischemic rats support beneficial effects of RSV on spatial memory retention. DISCUSSION: Our findings uncover time- and dose-related effects of RSV and global ischemia on the regulation of hippocampal plasticity. Changes in neuro- and angiogenesis are consistent with RSV neuroprotective effects, but appear independent of RSV regulatory effects on corticosterone secretion.

Evidence of lasting dysregulation of neuroendocrine and HPA axis function following global cerebral ischemia in male rats and the effect of Antalarmin on plasma corticosterone level.

Abnormal function of the neuroendocrine stress system has been implicated in the behavioral impairments observed following brain ischemia. The current study examined long-term changes in stress signal regulation 30days following global cerebral ischemia. Experiment 1 investigated changes in the expression of corticotropin releasing hormone (CRH) and its subtype 1 receptor (CRHR1), glucocorticoid receptors (GR) in the paraventricular nucleus of the hypothalamus (PVN), the central nucleus of the amygdala (CeA), and the CA1 subfield of the hippocampus. Tyrosine hydroxylase (TH) was determined at the locus coeruleus (LC). Experiment 2 investigated the role of central CRHR1 activation on corticosterone (CORT) secretion at multiple time intervals following global ischemia after exposure to an acute stressor. Findings from Experiment 1 demonstrated a persistent increase in GR, CRH and CRHR1 immunoreactivity (ir) at the PVN, reduced GR and CRHR1 expression in pyramidal CA1 neurons, and increased LC TH expression in ischemic rats displaying working memory errors in the radial arm Maze. Findings from Experiment 2 revealed increased CORT secretion up to 7 days, but no longer present 14 and 21 days post ischemia. However upon an acute restraint stress induced 27 days following reperfusion, ischemic rats had increased plasma CORT secretions compared to sham-operated animals, suggesting HPA axis hypersensitivity. Antalarmin (2 µg/2 µl) pretreatment significantly attenuated post ischemic elevation of basal and stress-induced CORT secretion. These findings support persistent neuroendocrine dysfunctions following brain ischemia likely to contribute to emotional and cognitive impairments observed in survivors of cardiac arrest and stroke.

Selective estrogen receptor activation prior to global cerebral ischemia in female rats impacts microglial activation and anxiety-like behaviors without effects on CA1 neuronal injury.

Estrogen receptor (ER) activation by 17-ß estradiol (E2) can attenuate neuronal injury and behavioral impairments following global cerebral ischemia (GCI) in rodents. This study sought to further examine the discrete roles of ERs through characterization of the effects of selective ER activation on post-ischemic pro-inflammatory microglial activation, hippocampal neuronal injury, and anxiety-like behaviors. Forty-six ovariectomized (OVX) adult female Wistar rats received daily s.c injections (100 µg/kg/day) of propylpyrazole triol (PPT; ERα agonist), diarylpropionitrile (DPN; ERß agonist), G-1 (G-protein coupled ER agonist; GPER), E2 (activating all receptors), or vehicle solution (VEH) for 21 days. After final injection, rats underwent GCI via 4-vessel occlusion (n=8 per group) or sham surgery (n=6, vehicle injections). The Open Field Test (OFT), Elevated Plus Maze (EPM), and Hole Board Test (HBT) assessed anxiety-like behaviors. Microglial activation (Iba1, CD68, CD86) in the basolateral amygdala (BLA), CA1 of the hippocampus, and paraventricular nucleus of the hypothalamus (PVN) was determined 8 days post-ischemia. Compared to sham rats, Iba1 activation and CA1 neuronal injury were increased in all ischemic groups except DPN-treated rats, with PPT-treated ischemic rats also showing increased PVN Iba1-ir expression. Behaviorally, VEH ischemic rats showed slightly elevated anxiety in the EPM compared to sham counterparts, with no significant effects of agonists. While no changes were observed in the OFT, emotion regulation via grooming in the HBT was increased in G-1 rats compared to E2 rats. Our findings support selective ER activation to regulate post-ischemic microglial activation and coping strategies in the HBT, despite minimal impact on hippocampal injury.

The cycle of stress: A systematic review of the impact of chronic psychological stress models on the rodent estrous cycle.

Stress is known to impair reproduction through interactions between the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes. However, while it is well accepted that stress can alter estrous cycle regularity, a key indicator of female's HPG axis function, effects of different types of psychological stress have been inconsistent. This systematic review evaluated the impact of rodent models of psychological stress on estrous cyclicity, while reporting biological parameters pertaining to HPA or HPG axis function assessed within these studies. We performed a systematic database search and included articles that implemented a psychological stress model in rodents and reported estrous cyclicity for at least two cycles after initiation of stress. Of the 32 studies included, 62.5% reported post-stress alterations to estrous cyclicity, with Chronic Mild Stress (CMS) models showing the most conclusive effects. Twenty-five studies measured HPG or HPA axis markers, with cycle disruptions being commonly observed in parallel with altered estradiol and increased corticosterone levels. Our review highlights gaps in reporting estrous cyclicity assessments and makes recommendations to improve comparability between studies.

Global cerebral ischemia in adult female rats interrupts estrous cyclicity and induces lasting changes in hypothalamic-pituitary-gonadal axis signaling peptides.

Persistent post-ischemic alterations to the hypothalamic-pituitary-adrenal (HPA) axis occur following global cerebral ischemia (GCI) in rodents. However, similar effects on hypothalamic-pituitary-gonadal (HPG) axis activation remain to be determined. Therefore, this study evaluated the effects of GCI in adult female rats (via four-vessel occlusion) on the regularity of the estrous cycle for 24-days post ischemia. A second objective aimed to assess persistent alterations of HPG axis activation through determination of the expression of estrogen receptor alpha (ERα), kisspeptin (Kiss1), and gonadotropin-inhibitory hormone (GnIH/RFamide-related peptide; RFRP3) in the medial preoptic area (POA), arcuate nucleus (ARC), dorsomedial nucleus (DMH) of the hypothalamus, and CA1 of the hippocampus 25 days post ischemia. Expression of glucocorticoid receptors (GR) in the paraventricular nucleus of the hypothalamus (PVN) and CA1 served as a proxy of altered HPA axis activation. Our findings demonstrated interruption of the estrous cycle in 87.5 % of ischemic rats, marked by persistent diestrus, lasting on average 11.86 days. Moreover, compared to sham-operated controls, ischemic female rats showed reduced Kiss1 expression in the hypothalamic ARC and POA, concomitant with elevated ERα in the ARC and increased GnIH in the DMH and CA1. Reduced GR expression in the CA1 was associated with increased GR-immunoreactivity in the PVN, indicative of lasting dysregulation of HPA axis activation. Together, these findings demonstrate GCI disruption of female rats' estrous cycle over multiple days, with a lasting impact on HPG axis regulators within the reproductive axis.

Bloody stressed! A systematic review of the associations between adulthood psychological stress and menstrual cycle irregularity.

Regular menstruation is a key indicator of general health and irregular menstrual parameters have been associated with elevated risk of adverse health outcomes. While psychological stress is believed to contribute to abnormal menstruation, little is known of the effects of discrete psychological stressors, including the COVID-19 pandemic, on menstrual function. A systematic database search was performed and studies investigating the relation between psychological stress and menstrual cycle irregularity in otherwise healthy adults were included. Two independent investigators completed abstract and full-text screening, data extraction, and risk of bias assessment. In the 41 included studies, a variety of stressors were assessed, namely COVID-19 pandemic stress, academic stress, and occupational stress. Our review found most studies report an association between psychological stress and menstrual dysfunction, with the most common disruptions being irregular menstruation and abnormal menstrual flow. Our findings also underlined notable discrepancies in the operational definitions used in the study of menstrual disorders. These observations emphasize the importance of psychological stress as a modifiable risk factor associated with irregular menstruation.

Repeated resveratrol administration confers lasting protection against neuronal damage but induces dose-related alterations of behavioral impairments after global ischemia.

Resveratrol, a naturally occurring polyphenol, has been shown to protect the heart and brain against ischemic injury. The current study investigated the effects of administration with either a 1 or 10-mg/kg dose of resveratrol on CA1 neuronal injury and behavioral/cognitive impairments after 10-min global ischemia in rats. The open-field, eight-arm radial maze and object recognition tests served to evaluate effects of resveratrol treatment on ischemia-induced locomotor activity, and spatial and recognition memory impairments, respectively. CA1 and CA3 neuronal injury was assessed upon completion of behavioral testing, 85 days postischemia. A separate series of groups served to assess neuronal injury at 7 days postischemia. Global ischemia (10 min) led to approximately 50% CA1 cell injury, which was prevented at both short (7 days) and long (85 days) postischemic intervals by resveratrol treatment. Importantly, despite comparable neuronal protection, the two resveratrol doses showed distinct behavioral effects. Thus, the 10-mg/kg resveratrol dose led to an enhanced locomotor activity in the open-field 4-days postischemia and an impaired spatial memory in the delayed nonmatching to sample and delayed matching to sample radial-maze tasks initiated on day 13 postischemia. These findings suggest independent actions of resveratrol on distinct physiological systems mediating cellular survival and functional recovery and dose-related actions of the polyphenol on behavioral and memory processes.

Short-Term Fish Oil Supplementation during Adolescence Supports Sex-Specific Impact on Adulthood Visuospatial Memory and Cognitive Flexibility.

Numerous studies have supported benefits of omega-3 supplementation using Menhaden fish oil (FO) to promote brain maturation and plasticity during critical developmental periods. The goal of this study was to determine sex-specific immediate and delayed impact of adolescent omega-3 supplementation on visuospatial memory and cognitive flexibility. Sixty-four Wistar rats (n = 32 males and females) received daily FO or soybean oil (CSO) supplementation via oral gavage (0.3 mL/100 g body weight) from postnatal day 28-47. The Barnes Maze Test (BMT) was used to measure visuospatial memory and reversal learning trials (RL) determined cognitive flexibility. Juveniles underwent testing immediately after the gavage period, while adults began testing on postnatal day 90. Adult rats showed reduced working memory errors (WME) and gradual decrease in escape latencies compared to juveniles. Importantly, adult FO-supplemented females displayed fewer WME than males, while males' performance benefited from CSO supplementation. Overall, sex- and supplementation-dependent effects supported a positive impact of FO in female rats only. Our findings support the potential for supplementation limited to the early adolescence period to influence adulthood spatial learning and cognitive flexibility in a sex-specific manner.

Women with Myocardial Infarction Present Subtle Cognitive Difficulties on a Neuropsychological Battery After Exposure to a Social Stressor.

Objective: Myocardial infarction (MI) is the primary cause of mortality and morbidity in women, but its sequelae remain largely understudied. Given the heart-brain relationship, our study aimed to further understand stress's impact on regulating cognitive function post-MI. Specifically, our study evaluated the effect of stress induced using the Trier Social Stress Test (TSST), on neuropsychological function in women who have or have not experienced MI. Methodology: To do so, women (mean age = 59.41 yrs) with (WHxMI = 13) or without () a history of MI were exposed to the TSST prior to completion of a series of standardized neuropsychological tests: the Montreal Cognitive Assessment (MoCA), Control Oral Word Association (COWA), Rey Complex Figure and Recognition (RCFT), Trail Making Test (TMT), and Auditory Consonant Triagrams (ACT). Results: Our findings support MI to be associated with impairments in working memory affecting immediate recall of ACT, as well as visuospatial impairments in the RCFT copy trial, marked by poorer drawing accuracy and incorrect placement of figure elements. Overall, WHxMI required more time to complete the neuropsychological assessment (WHxMI 166.57 ± 12, 155.00 ± 6.57; p < 0.01). Conclusion: Together, these findings support cognitive impairments noted following a social stressor to remain subtle in WHxMI. Our study highlights the need for the development of more sensitive tools to screen for neuropsychological impairments in women with MI and the importance of assessing performance in a variety of testing conditions.

Predictive value of baseline cognitive functioning on health-related quality of life in individuals with coronary artery disease: a 5-year longitudinal study.

AIMS: Emerging studies suggest an association exists between coronary artery disease (CAD) and the development of neurodegenerative diseases, with CAD acting as a precursor. Our study aimed to investigate the relationship between baseline measures of cognitive functioning and long-term health-related quality of life (HRQoL) in individuals with CAD with specification to Type D personality traits and sex. METHODS AND RESULTS: This prospective observational cohort study consisted of 864 participants (mean age 58 SD = 9 years, 74.0% men) with CAD after acute coronary syndrome. Baseline characteristics included comprehensive cognitive testing, measures of sociodemographic and clinical factors, and psychological assessment scales, such as Type D personality scale and the Hospital Anxiety and Depression scale. The Minnesota Living with Heart Failure Questionnaire assessed participants' HRQoL, conducted through phone interviews at baseline, every 6 months for up to 2 years, and after 5 years. Cognitive functioning correlated with HRQoL at all time intervals over the 5-year follow-up. Regarding sex and Type D personality, significant differences emerged in associations between impaired cognitive functioning at baseline and HRQoL measured over the period of 5 years. Men participants with characteristics of Type D personality were especially vulnerable to impaired cognitive functioning affecting the 5-year quality of life. CONCLUSION: Men with CAD who obtained scores indicating characteristics of Type D personality were significantly more likely to have lower baseline cognitive functions and long-term HRQoL outcomes. This information could inform healthcare practitioners to screen for personality characteristics and closely follow-up those at a greater risk.

Contribution of Obstructive Sleep Apnoea to Cognitive Functioning of Males With Coronary Artery Disease: A Relationship With Endocrine and Inflammatory Biomarkers.

Introduction: Our exploratory study aimed to determine whether obstructive sleep apnoea (OSA) could affect cognitive functioning in males with coronary artery disease (CAD), and whether such impact could be associated with changes in thyroid hormones and inflammatory marker regulation on cognitive functioning. Method: We evaluated different endocrine and inflammatory biomarkers, including free triiodothyronine [fT3], free tetraiodothyronine [fT4], N-terminal pro-B-type natriuretic peptide [NT-pro-BNP], and high-sensitivity C-reactive protein [hs-CRP] serum levels in 328 males ( x ¯ = 57 ± 10 years), undergoing cardiac rehabilitation after an acute coronary event. Participants underwent full-night polysomnography and were classified in mild/non-OSA (n = 253) and OSA (n = 75) according to an apnoea-hypopnoea index ≥ 15 event/h. Cognitive functioning testing included the Digit Span Test, Digit Symbol Test (DSST), and Trail Making Test. Analyses of variance assessed the impact of OSA on cognitive functioning and possible relationships of fT3/fT4, NT-pro-BNP and with hs-CRP on cognitive measures. Results: Significant group (OSA, mild/non-OSA) × NT-pro-BNP (<157.0 vs. ≥157.0, ng/L) interactions were found for the DSST raw score (F (2,324) = 3.58, p = 0.014). Decomposition of interactions showed that the DSST scores of the OSA group with NT-pro-BNP ≥ 157.0 ng/L (M = 33.2; SD = 8.1) were significantly lower, p = 0.031, than those of the mild/non-OSA with NT-pro-BNP < 157.0 ng/L (M = 37.7; SD = 8.9). Conclusion: These findings indicate that males with OSA and clinically elevated NT-pro-BNP levels experienced inferior psychomotor performance compared to those without OSA and reduced NT-pro-BNP levels.

Changes in HPA reactivity and noradrenergic functions regulate spatial memory impairments at delayed time intervals following cerebral ischemia.

This study investigates the association of ischemia-induced spatial memory impairment to alterations of the HPA axis and noradrenergic activation post insult. Experiment 1 characterized the effects of 10 min forebrain ischemia on corticosterone (CORT) secretion following ischemia and in response to spatial memory assessment in the Barnes maze, as well as the impact of pre-ischemia treatment with the glucocorticoid inhibitor metyrapone (175 mg/kg; s.c.). The results showed that cerebral ischemia represents a significant physiological stressor that upregulated CORT secretion 1, 24 and 72 h post-ischemia but not at 7 days. In response to testing in the Barnes maze ischemic animals showed elevated CORT secretion simultaneously with spatial memory deficits. The single dose of metyrapone attenuated the ischemia-induced adrenocortical hyper-responsiveness and subsequent memory deficits despite not providing neuroprotection in the hippocampal CA1 pyramidal cells. To complement these findings, we examined whether norepinephrine which provides positive feedback to the HPA axis and is upregulated following brain ischemia could influence memory performance at delayed intervals after ischemia. Experiment 2 demonstrated that pre-testing administration of the alpha2-adrenoceptor agonist clonidine (.04 mg/kg, s.c.) attenuated ischemia-induced working memory impairments in a radial maze while opposite effects were obtained with the antagonist yohimbine (.3 mg/kg, s.c.). Post-testing administration of clonidine produced spatial reference memory impairments in ischemic rats. The findings from the current study demonstrate increased sensitization and responsiveness of systems regulating stress hormones at long intervals post ischemia. Importantly, we demonstrate that these effects contribute to post ischemic cognitive impairments which can be attenuated pharmacologically even in the presence of hippocampal degeneration at time of testing.

Global cerebral ischemia in adolescent male Long Evans rats: Effects of vanillic acid supplementation on stress response, emotionality, and visuospatial memory.

The developmental period is critical in delineating plastic response to internal and external events. However, neurobehavioural effects of global cerebral ischemia (GCI) in the maturing brain remain largely unknown. This study characterised the effects of GCI experienced at puberty on adulthood (1) hippocampus CA1 neuronal damage, (2) cognitive and emotional impairments, and (3) glucocorticoid receptor (GR) expression. Effects of adolescent exposure to the phenol vanillic acid (VA) on post-ischemic outcomes were also determined. Male Long Evans rats (n = 35) were supplemented for 21 consecutive days (postnatal days 33-53) with VA (91 mg/kg) or nut paste vehicle (control) prior to a 10-min GCI or sham surgery. As adults, rats were tested in the Open Field Test (OFT), Elevated-Plus Maze (EPM), and Barnes Maze (BM). GR expression was determined in the basolateral amygdala (BLA), CA1, and paraventricular nucleus (PVN), and brain injury assessed via CA1 neuronal density. Adolescent GCI exposure induced extensive hippocampal CA1 injury, which was not prevented by VA supplementation. Behaviourally, GCI increased EPM exploration while having no impact on spatial memory. VA intake increased OFT peripheral exploration. Notably, while no delayed changes in CA1 and PVN GR immunoreactivity were noted, both treatments separately increased BLA GR expression when compared with sham-nut paste rats. Age at GCI occurrence plays a critical role on post-ischemic impairments. The observation of minimal functional impairments despite important CA1 neuronal damage supports use of compensatory mechanisms. Our findings also show daily VA supplementation during adolescence to have no protective effects on post-ischemic outcomes, contrasting adult intake.

Global Cerebral Ischemia in Male Long Evans Rats Impairs Dopaminergic/ΔFosB Signalling in the Mesocorticolimbic Pathway Without Altering Delay Discounting Rates.

Global cerebral ischemia (GCI) in rats has been shown to promote exploration of anxiogenic zones of the Elevated-Plus Maze (EPM) and Open Field Test (OFT). This study investigated changes in impulsive choice and/or defensive responses as possible contributors of heightened anxiogenic exploration observed after ischemia. Impulsivity was assessed using delay discounting (DD) paradigms, while the Predator Odour Test (PO) served to assess changes in defensive responses towards a naturally aversive stimulus. Male Long Evans rats underwent 9 days of autoshaping training and 24 days of DD training prior to GCI or sham surgery (n = 9/group). Post-surgery, rats completed the OFT, EPM, and PO, followed by 6 days of DD sessions. Blood droplets served to evaluate corticosterone secretion associated with PO exposure. With impulsivity being regulated through mesocorticolimbic monoaminergic pathways, we also characterised post-ischemic changes in the expression of dopamine D2 receptors (DRD2), dopamine transporters (DAT), and 1FosB in the basolateral amygdala (BLA), nucleus accumbens core (NAcC) and shell (NAcS), and ventromedial prefrontal cortex (vmPFC) using immunohistofluorescence. Our findings revealed no impact of GCI on delay discounting rates, while PO approach behaviours were minimally affected. Nonetheless, GCI significantly reduced DRD2 and ΔFosB-ir in the NAcS and NAcC, respectively, while DAT-ir was diminished in both NAc subregions. Collectively, our findings refine the understanding of cognitive-behavioural and biochemical responses following stroke or cardiac arrest. They support significant alterations to the dopaminergic mesocorticolimbic pathway after ischemia, which are not associated with altered impulsive choice in a DD task but may influence locomotor exploration of the OFT and EPM.

Adult Male Rats Show Resilience to Adolescent Bisphenol A Effects on Hormonal and Behavioral Responses While Co-Exposure With Hop Extracts Supports Synergistic Actions.

The adolescence period, marked by sexual and brain maturation, has shown sensitivity to various environmental disruptors. Exposure to the xenoestrogen bisphenol A (BPA) is known to alter physiological and behavioral responses although its role at this critical period remains largely unknown. Recent research further suggests biochemical and genomic effects of BPA to be mitigated by various natural compounds, while effects on behavior have not been examined. This study aimed to characterize (1) the effects of dietary BPA during adolescence on endogenous corticosterone (CORT) secretion, emotional behavior, and testosterone (T) in adulthood, and (2) the impact of combined exposure to BPA with hop extracts (Hop), a phytoestrogen with anxiolytic properties. To do so, four groups of male Wistar rats [postnatal day (PND) 28] were administered corn oil (control), BPA (40 mg/kg), hops (40 mg/kg), or BPA-hops by oral gavage for 21 days (PND 28-48). Blood droplets collected on PND 28, 48, and 71 served to measure CORT and T changes. As adults, rats were tested in the elevated plus maze (EPM), the social interaction test, and the forced swim test. Our findings demonstrated elevated anxiety and a trend toward depressive-like behaviors in BPA- compared to hops-exposed rats. However, BPA intake had no impact on basal CORT levels, or adulthood T secretion and sociability. Of note, BPA's anxiogenic effect manifested through decreased EPM open arm entries was abolished by hops co-supplementation. Together, our observations suggest the adolescence period to be less sensitive to deleterious effects of BPA than what has been reported upon gestational and perinatal exposure.

Ischemia-induced hyperactivity: effects of dim versus bright illumination on open-field exploration and habituation following global ischemia in rats.

The current study reports the impact of different illumination conditions on exploratory activity following global ischemia in rats. Exploratory activity was tested at different post-ischemic intervals under bright (450 lux) or dim (40 lux) light exposure. A 30 min testing period performed 5 days post-reperfusion examined within-session open-field habituation in ischemic and sham-operated animals. Additional animals were tested in the open-field under the two illumination conditions for shorter 10 min tests on days 3, 6, and 9 following reperfusion. Our findings demonstrated illumination-related activity profile in the open-field in ischemic animals. While ischemic rats showed increased activity when tested under bright open-field illumination, reduced activity was observed under dim illumination as compared to sham-operated controls. Further, habituation deficits were not apparent in animals subjected to global ischemia under any illumination condition. Similar behavioral profiles and habituation were observed in ischemic animals when exposed to repetitive open-field tests at days 3, 6, and 9 following reperfusion. CA1 neuronal injury (approximately 75% as compared to sham rats) was comparable in all ischemic groups at day 12 following reperfusion. The present findings suggest that differences in initial behavioral reactivity of sham and ischemic rats to bright versus dimly lighted environments may contribute to differences in open-field exploration reported between these groups. They also challenge the notion that deficits in exploration in ischemic animals are mainly attributable to processes related to habituation, or that hyperactivity represents a reliable predictor of CA1 neuronal injury. These observations may help explain discrepant ischemia-induced behavioral effects reported in the open field.

Food restriction attenuates ischemia-induced spatial learning and memory deficits despite extensive CA1 ischemic injury.

The purpose of the present study was to examine whether short-term food restriction (40% less food over a 3-month period) can attenuate ischemia-induced CA1 neuronal degeneration, and whether this attenuation translated into improved recovery of functional impairments following global ischemia. There was a significant loss of pyramidal CA1 neurons in ischemic compared to sham-operated rats but no difference between the ad lib and food-restricted ischemic animals. Although the diet did not influence neuronal damage in ischemic animals, the performance of food-restricted ischemic rats in spatial task such as the radial arm maze was significantly better than that of ad lib fed ischemic rats. Food-restricted ischemic rats made equivalent numbers of working memory errors as sham-operated animals and took the same time to complete a standard 8-arm radial arm maze task. They also displayed higher activity level in the open field compared to ad libitum fed ischemic rats, and spent considerably more time in the open arms of the elevated plus maze compared to the other groups, suggesting decreased anxiety in these ischemic rats. The relative sparing of spatial memory performance in food-restricted ischemic animals suggests that food restriction facilitates functional recovery.