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Effect of the combination of restraint stress and corticosterone injection in the Novel object recognition task. A- Represents the exploratory time between the two objects. B- Represents discrimination index. N = 7. All the data are expressed as Mean ± SEM. bp < 0.05 when compare to control; #p < 0.05 when compare to CORT;* p < 0.05; when compare to RS. ANOVA followed by Student Newman - Keuls test. CORT: Corticosterone; RS: Restraint stress CORT + RS = corticosterone + restraint stress
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Many models, such as chronic mild stress, chronic stress or chronic corticosterone injections are used to induce depression associated with cognitive deficits. However, the induction period in these different models is still long and face constraints when it is short such as in the chronic mild stress done in a minimum period of 21 days. This study...
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Background:
Parkinson's disease (PD) is typically characterized by impairment of motor function. Gait disturbances similar to those observed in patients with PD can be observed in animals after injection of neurotoxin 6-hydroxydopamine (6-OHDA) to induce unilateral nigrostriatal dopamine depletion. Exercise has been shown to be a promising non-pha...
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... Previous studies by us and others indicate that chronic administration of CORT could continuously exacerbate depressionlike behaviors and neurochemical alterations with recurrent episodes in animal models, implying the need to develop therapeutic interventions (Lebedeva et al., 2020). Due to the characterized behaviors and molecular profiles in both restraint stress and CORT stress models (Gregus et al., 2005;Ngoupaye et al., 2018), we selected these animal models to investigate the anti-depressive effects of NHQXW. As expected, the anxiety-and depressive-like behaviors in the restraint stress mice were remarkably attenuated by treatment with NHQXW which had similar effects to FLX. ...
Introduction: Chronic stress-associated hormonal imbalance impairs hippocampal neurogenesis, contributing to depressive and anxiety behaviors. Targeting neurogenesis is thus a promising antidepressant therapeutic strategy. Niuhuang Qingxin Wan (NHQXW) is an herbal formula for mental disorders in Traditional Chinese Medicine (TCM) practice, but its anti-depressant efficacies and mechanisms remain unverified.
Methods: In the present study, we tested the hypothesis that NHQXW could ameliorate depressive-like behaviors and improve hippocampal neurogenesis by modulating the TrkB/ERK/CREB signaling pathway by utilizing two depression mouse models including a chronic restraint stress (CRS) mouse model and a chronic corticosterone (CORT) stress (CCS) induced mouse model. The depression-like mouse models were orally treated with NHQXW whereas fluoxetine was used as the positive control group. We evaluated the effects of NHQXW on depressive- and anxiety-like behaviors and determined the effects of NHQXW on inducing hippocampal neurogenesis.
Results: NHQXW treatment significantly ameliorated depressive-like behaviors in those chronic stress mouse models. NHQXW significantly improved hippocampal neurogenesis in the CRS mice and CCS mice. The potential neurogenic mechanism of NHQXW was identified by regulating the expression levels of BDNF, TrkB, p-ERK (T202/T204), p-MEK1/2 (S217/221), and p-CREB (S133) in the hippocampus area of the CCS mice. NHQXW revealed its antidepressant and neurogenic effects that were similar to fluoxetine. Moreover, NHQXW treatment revealed long-term effects on preventing withdrawal-associated rebound symptoms in the CCS mice. Furthermore, in a bioactivity-guided quality control study, liquiritin was identified as one of the bioactive compounds of NHQXW with the bioactivities of neurogenesis-promoting effects.
Discussion: Taken together, NHQXW could be a promising TCM formula to attenuate depressive- and anxiety-like behaviors against chronic stress and depression. The underlying anti-depressant mechanisms could be correlated with its neurogenic activities by stimulating the TrkB/ERK/CREB signaling pathway.
... The MWM test has gained significance in assessing memory in stress models. It relies on reduced escape time and decreased time spent in the designated quadrant as reliable indicators of memory impairment [50][51][52]. These effects are believed to be consequences of serotonin deficiency [36], inflammation, and/or oxidative stress following cortisol overproduction [53]. ...
Depression presents a significant global health burden, necessitating the search for effective and safe treatments. This investigation aims to assess the antidepressant effect of the hydroethanolic extract of Anacardium occidentale (AO) on depression-related behaviors in rats. The depression model involved 42 days of unpredictable chronic mild stress (UCMS) exposure and was assessed using the sucrose preference and the forced swimming (FST) test. Additionally, memory-related aspects were examined using the tests Y-maze and Morris water maze (MWM), following 21 days of treatment with varying doses of the AO extract (150, 300, and 450 mg/kg) and Imipramine (20 mg/kg), commencing on day 21. The monoamines (norepinephrine, serotonin, and dopamine), oxidative stress markers (MDA and SOD), and cytokines levels (IL-1β, IL-6, and TNF-α) within the brain were evaluated. Additionally, the concentration of blood corticosterone was measured. Treatment with AO significantly alleviated UCMS-induced and depressive-like behaviors in rats. This was evidenced by the ability of the extract to prevent further decreases in body mass, increase sucrose consumption, reduce immobility time in the test Forced Swimming, improve cognitive performance in both tests Y-maze and the Morris water maze by increasing the target quadrant dwelling time and spontaneous alternation percentage, and promote faster feeding behavior in the novelty-suppressed feeding test. It also decreased pro-inflammatory cytokines, corticosterone, and MDA levels, and increased monoamine levels and SOD activity. HPLC-MS analysis revealed the presence of triterpenoid compounds (ursolic acid, oleanolic acid, and lupane) and polyphenols (catechin quercetin and kaempferol). These results evidenced the antidepressant effects of the AO, which might involve corticosterone and monoaminergic regulation as antioxidant and anti-inflammatory activities.
... The experimental combination decreased AChE activity and returned it to control levels. AChE, being the enzyme that breaks down acetylcholine is fundamental for correct cholinergic transmission and its excessive activity has been many times shown to be associated with cognitive and memory impairments in different experimental models [149][150]. However, excessive AChE activity is further detrimental by aggravating AD pathology by interacting with Aβ and promoting amyloid fibril formation and by forming AChE-Aβ complexes which are more harmful than the amyloid fibrils alone [151][152]. ...
Alzheimer’s disease manifests itself as a complex pathological condition with neuroinflammation, oxidative stress and cholinergic dysfunction being a few of the many pathological changes. Due to the complexity of the disease current therapeutic strategies aim at a multitargeted approach often relying on a combination of sub-stances with versatile and complementary effects. In the present study, unique combination of α-lipoic acid, citicoline, extracts of leaves from olive tree and green tea, Vitamin D3, selenium and an immune supporting complex was tested in a scopolamine-induced dementia in rats. Using behavioral and biochemical methods we assessed the effects of this combination on learning and memory, and elucidated the mechanisms under-lying its effects. Our results showed that as compared to the components, experimental combination was most efficient in improving short- and long-term memory assessed by the step-through method as well as spatial memory, assessed by T-maze and Barnes maze underlying decrease in AChE activity and LPO, in-creases in SOD activity in cortex; activities of catalase and GPx, levels of BDNF and pCREB in the hippocam-pus. No significant histopathological changes or blood parameter changes were detected, making the experi-mental combination an effective and safe candidate in a multitargeted treatment of AD.
... To avoid animals mating in each group we kept them separated according to the sex during the waiting time and the test period. The distribution was done according to Miller et al., 2017, and our previous studies, where this gender distribution was not having an influence in the responses, and has limited sexual dimorphism overall group effect (Foutsop et al., 2023;Ngoupaye et al., 2018Ngoupaye et al., , 2020a. We also considered previous studies that have shown that female are more sensitive than male mice to scopolamine effect on water maze performance (Berger-Sweeney et al., 1995;Giacobini and Pepeu,2018) and that Ach released in the hippocampus is similar between male and female in light period (period used during our experiments) (Mitsushima, 2011;Giacobini and Pepeu, 2018). ...
... Concerning the probe test, the platform was removed from the pool and the animal was allowed to locate the position of the quadrant where the platform used to be, for a total duration of 1 min. The time spent in the quadrant containing the platform was measured, and the latency to reach the platform was measured and noted as the index of acquisition and learning (Ngoupaye et al., 2018). ...
... The hippocampus was grinded in a 0.1 M phosphate buffer containing 1% Triton-100X (P H 7.4) (10% w/v) in a porcelain mortar to produce. The homogenates were later centrifuged for 15 min (3000 rpm), and the supernatant was collected for various assays (Ngoupaye et al. 2018). ...
Capparis sepiaria (Capparaceae) is a plant used in African traditional medicine to treat psychiatic disorders. The aim of this study was to assess the anti-amnesic effect of aqueous lyophilisate of the root bark of Capparis sepiaria (C. sepiaria) on scopolamine-induced animal model of memory impairment using Swiss albino adult mice of both sexes. Memory integrity was assessed by Morris water Maze test, Novel Object Recognition (NOR) and Object-location memory (OLT) tasks were used to assess behavioural components of memory processes and learning. Malondialdehyde (MDA), reduced glutathione (GSH), NO levels and catalase were used to assess oxidative stress while acethylcholinesterase activity was used to evaluate acetylcholine activity in the hippocampus tissues. The quantitative phytochemistry and acute toxicity of the roots of C. sepiaria were also evaluated. The aqueous lyophilisate of C. sepiaria at doses of 10 mg/kg and 40 mg/kg significantly increased the discrimination index in the Morris Water Maze and the objet location tasks. The aqueous lyophilisate of C. sepiaria significantly increased hippocampal GSH and catalase levels and decreased hippocampal MDA, NO levels and achetylcholinesterase (AChE) activities. The aqueous lyophilisate of C. sepiaria showed no acute toxicity with a LD50 > 5000 mg/kg, and revealed a content of flavonoids, tannins and phenols. These results suggest that C. sepiaria improve memory impairment induced by scopolamine and therefore possess antiamnesic properties. These properties would result from a modulation of cholinergic neurotransmission as well as an antioxidant activity of the plant.
... In a porcelain mortar, the hippocampi were ground (10% w/v). Each of the homogenates was prepared using a 0.1 M phosphate buffer solution containing 1% Triton-100 X (PH 7.4) and was individually centrifuged (3000 rpm) for 15 min [40]. ...
... Chronic stress is a major contributor to the development of depression [54]. To mimic chronic stress, the stress induced by chronic restriction [40] has been used. The Sucrose preference test (SPT) is a test that shows the preference of animals for sweet substances that produce pleasure. ...
... The Sucrose preference test (SPT) is a test that shows the preference of animals for sweet substances that produce pleasure. Reduction in sucrose preference ratio assessed during the sucrose preference test, relative to a control group is defined as anhedonia and healthy animals usually show a preference for the sugary solution while anhedonic animals tend to consume less [40,[55][56]. This study shows that C. sepiaria was able to prevent anhedonia in groups pretreated with the lyophilizate like fluoxetine (10mg/kg). ...
Background: Major Depressive Disorder is a common mental illness characterized by persistent low mood, cognitive impairment, anhedonia, weight gain, or loss and several other symptoms, ranging from psychomotor to cognitive impairments. Commonly available antidepressants show side effects and limited efficacy; therefore, an alternative is to be considered. Capparis sepiaria (Capparaceae) is a plant used in traditional medicine to treat mental disorders. The aim of this study was to investigate possible antidepressant-like effects of the aqueous lyophilizate of Capparis sepiaria in Wistar rats. Methods: Depressive-like behavior was induced using restraint stress for 14 days. The forced swimming test, the open field test, the sucrose preference test, body weight, and the food consumption were done to assess depressive-like behavior. On day 15 animals were sacrificed and the adrenal glands mass and the hippocampi were collected for Hypothalamo-pituitary-axis activity and oxidative stress markers assessment. Results: The aqueous lyophilizate of the root bark of Capparis sepiaria increased swimming time and decreased immobility time (p<0.001) in the forced swimming test and, increased sucrose consumption in the sucrose preference test (p<0.001). In the open field test, there was no difference in the number of lines crossed between groups. Chronic stress significantly increased adrenal weight (p<0.05) which was prevented by the aqueous lyophilizate of Capparis sepiaria at the dose 10 mg/kg. Chronic stress decreased food consumption and weight which was prevented by the aqueous lyophilizate of Capparis sepiaria. The lyophilizate increased the reduced glutathione (GSH) level (p<0.001), and Catalase activity (p<0.001), and decreased the malondialdehyde level (p<0.001) in the determination of some oxidative stress markers. Conclusion: These results suggest that the aqueous lyophilizate of the roots bark of C. sepiaria possesses antidepressant-like effects. Keywords: Depression; Capparis sepiaria; restraint stress; oxidative stress.
... Due to this potential ethological caveat, it has been strongly suggested that contextually valid experimental designs are needed to strengthen the translational value of studies like MBT (53). To this end, the application of a chronic stress paradigm, used to evoke extended hedonic deficit and other depressive-like symptoms in rodents, such as reduced motivation, increased aggression, anxiety, and overall reduction in well-being, is widely considered to have significant aetiological relevance and can serve as a valid preclinical model for various human psychiatric disorders (65)(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78). ...
... To appropriately assess the anxiolytic potential of our NPDs we developed a seven-day mild chronic stress paradigm (MCSP) involving a combined oral corticosterone exposure (25 µg/mL introduced into drinking water for seven days) with a daily 30-min restraint stress session using a ventilated restrainer for the last five days of the protocol. It has been shown by others that the combination of these stress inducing methods leads to more severe depression and anxiety-like behaviours, producing earlier onset of cognitive deficit in conditioned mice (76). Indeed, when evaluated using the MBT, mice subjected to the MCSP exhibited a significant induction in marble burying behaviour over the unstressed (control) group ( Figure 5). ...
... Interestingly, this elevated level of stress persisted to the same extent 7 days after MCSP conditioning. It is important to note that this sustained cognitive deficiency was established after only seven days of chronic stress exposure, a period of induction considerably shorter than previously reported (75,76). Several studies have reported the successful treatment of severe anxiety after a single oral dose of psilocybin, especially in patients struggling with cancer-related distress (CRD) (13,79,80). ...
The psychedelic compound psilocybin has shown therapeutic benefit in the treatment of numerous psychiatric diseases. A recent randomized clinical trial conducted at Johns Hopkins Bayview Medical Center demonstrated the efficacy of psilocybin-assisted therapy in the treatment of Major Depressive Disorder (MDD). Similarly, a phase IIb study evaluating psilocybin-assisted therapy for treatment-resistant depression (TRD) presented statistically meaningful and long-term reduction in depressive symptoms. Also, many studies have reported the successful treatment of severe anxiety after a single oral dose of psilocybin, especially in patients struggling with cancer-related distress (CRD). Despite these compelling clinical results, concerns regarding the duration of the psychedelic experience produced by psilocybin pose a significant barrier to its widespread therapeutic application. Psilocybin, derived from magic mushrooms is the naturally occurring prodrug of the neuroactive compound psilocin. When orally administered, exposure to the acidic gastrointestinal (GI) environment together with enzymatic processing by intestinal and hepatic alkaline phosphatase lead to the dephosphorylation of psilocybin producing elevated levels of systemic psilocin. These plasma levels are detectable up to 24 h and produce a psychoactive episode lasting as long as 6 h post-ingestion. In order to positively modify the kinetics of the acute psychedelic response, we have engineered a library of novel prodrug derivatives (NPDs) of psilocin, introducing a diversity of alternative metabolically cleavable moieties modified at the 4-carbon position of the core indole ring. This library consists of twenty-eight unique compounds represented by nine distinct prodrug classes. Each molecule was screened in vitro for metabolic stability using isolated human serum, and human cellular fractions derived from liver and intestinal tissues. This screen revealed fifteen prodrugs that produced measurable levels of psilocin in vitro, with ester and thiocarbonate-based prodrug derivatives significantly represented. These fifteen NPDs were further evaluated for pharmacokinetic (PK) profiles in mice, assessing plasma levels of both residual prodrug and resultant psilocin. PK results confirmed the efficiency of ester and thiocarbonate-based prodrug metabolism upon oral and intravenous administration, achieving levels reduced, albeit comparable to levels of psilocybin-derived psilocin. Of note, almost all NPDs tested maintained reduced overall exposure of psilocin relative to psilocybin, with no measurable levels detected at 24 h post-dose. Finally, all NPDs were screened for CNS bioavailability in healthy mice using the Head Twitch Response (HTR), a behavioural biomarker of 5-HT2A receptor stimulation and an established proxy for psychoactive potential. Interestingly, five NPDs produced peak HTR that approached or exceeded levels induced by an equivalent dose of psilocybin. Among these bioactive prodrugs, an ester-based and thiocarbonate-based molecule produced long-term anxiolytic benefit in chronically stressed mice evaluated in the marble burying psychiatric model. Overall, this screening campaign identified novel candidate prodrugs of psilocin with altered metabolic profiles and reduced pharmacological exposure, potentially attenuating the duration of the psychedelic response. These molecules still maintained the long-term psychiatric and physiological benefits characteristic of psilocybin therapy. Additionally, these modified parameters also offer the opportunity for altered routes of administration bypassing conventional oral dosing.
... To further demonstrate the presence of deep brain lymphatic vessels and their regulation by stress using different approaches, we detected lymphatic vessel markers by flow cytometry and studied their regulation by chronic corticosterone treatment (alternative animal model of chronic stress) [23,24]. ...
Studies have demonstrated that a functional network of meningeal lymphatic vessels exists in the brain. However, it is unknown whether lymphatic vessels could also extend deep into the brain parenchyma and whether the vessels could be regulated by stressful life events. We used tissue clearing techniques, immunostaining, light-sheet whole-brain imaging, confocal imaging in thick brain sections and flow cytometry to demonstrate the existence of lymphatic vessels deep in the brain parenchyma. Chronic unpredictable mild stress or chronic corticosterone treatment was used to examine the regulation of brain lymphatic vessels by stressful events. Western blotting and coimmunoprecipitation were used to provide mechanistic insights. We demonstrated the existence of lymphatic vessels deep in the brain parenchyma and characterized their features in the cortex, cerebellum, hippocampus, midbrain, and brainstem. Furthermore, we showed that deep brain lymphatic vessels can be regulated by stressful life events. Chronic stress reduced the length and areas of lymphatic vessels in the hippocampus and thalamus but increased the diameter of lymphatic vessels in the amygdala. No changes were observed in prefrontal cortex, lateral habenula, or dorsal raphe nucleus. Chronic corticosterone treatment reduced lymphatic endothelial cell markers in the hippocampus. Mechanistically, chronic stress might reduce hippocampal lymphatic vessels by down-regulating vascular endothelial growth factor C receptors and up-regulating vascular endothelial growth factor C neutralization mechanisms. Our results provide new insights into the characteristic features of deep brain lymphatic vessels, as well as their regulation by stressful life events.
... In general, depression disturbs both declarative and nondeclarative memory (Bazin et al., 1994;Deuschle et al., 2004;Ellwart et al., 2003). Various research indicates that episodic-like memory is first disrupted in depressed individuals (de Almeida et al., 2020;Elizalde et al., 2008;Li et al., 2017a;Ngoupaye et al., 2018). In rodent depression models, we also can observe declarative and nondeclarative memory impairments, including spatial, recognition, or emotional memory deficits (D'Avila et al., 2018;de Almeida et al., 2020;Elizalde et al., 2008;Jianhua et al., 2017;Li et al., 2017a;Ngoupaye et al., 2018;Saghaei et al., 2020;Skórzewska et al., 2006;Song et al., 2006;Sung et al., 2010). ...
... Various research indicates that episodic-like memory is first disrupted in depressed individuals (de Almeida et al., 2020;Elizalde et al., 2008;Li et al., 2017a;Ngoupaye et al., 2018). In rodent depression models, we also can observe declarative and nondeclarative memory impairments, including spatial, recognition, or emotional memory deficits (D'Avila et al., 2018;de Almeida et al., 2020;Elizalde et al., 2008;Jianhua et al., 2017;Li et al., 2017a;Ngoupaye et al., 2018;Saghaei et al., 2020;Skórzewska et al., 2006;Song et al., 2006;Sung et al., 2010). Moreover, executive functions, such as working memory, are altered in depression and animal models of depression (Gärtner et al., 2018;McDonnell et al., 2020;Yu et al., 2011). ...
... Both alpha-lipoic acid and desvenlafaxine reversed these changes (de Sousa et al., 2018). The combined corticosterone treatment and chronic restraint stress also induced memory decline with the increased acetylcholinesterase activity (Ngoupaye et al., 2018). Another herbal formula, Bombax costatum Pellegr. ...
More than 80% of depressed patients struggle with learning new tasks, remembering positive events, or concentrating on a single topic. These neurocognitive deficits accompanying depression may be linked to functional and structural changes in the prefrontal cortex and hippocampus. However, their mechanisms are not yet completely understood. We conducted a narrative review of articles regarding animal studies to assess the state of knowledge. First, we argue the contribution of changes in neurotransmitters and hormone levels in the pathomechanism of cognitive dysfunction in animal depression models. Then, we used numerous neuroinflammation studies to explore its possible implication in cognitive decline. Encouragingly, we also observed a positive correlation between increased oxidative stress and a depressive-like state with concomitant memory deficits. Finally, we discuss the undeniable role of neurotrophin deficits in developing cognitive decline in animal models of depression. This review reveals the complexity of depression-related memory impairments and highlights the potential clinical importance of gathered findings for developing more reliable animal models and designing novel antidepressants with procognitive properties.
... A study conducted by Choubey et al. (2019), has showed that restraint stress (RS) induces anxiety and depressive-like behavior. It is also implicated in the alteration of the learning and memory process; hence, resulting in the cognitive deficit (Ngoupaye et al., 2018). The aforementioned effects of restraint stress on the nervous system could be tired to its ability to induce oxidative damage shown by elevated brain levels of malondialdehyde (MDA), since MDA is an indicator of lipid peroxidation (Salehi et al., 2018). ...
Background: stress is an omnipresence phenomenon, and it's set to induce organs damage in most living organisms. The degree of organ damage is difficult to ascertain in humans; this has called for translational studies on animals to deduce the pathways by which stressor induce organ damage. Aim: To compare the effects poses on the system by the various stress paradigm use in physiological research. Methods: The literature were sourced from Google Scholar and PubMed database by typing the following keywords; stress, restraint stress, noise stress, heat stress and water immersion; about a 100 paper was read an 45 were careful selected based on relevance and year of publication. 90% of the papers were within 2015 to 2020 while the remaining 10% were before 2015. Results: Literature reviewed shows that restraint and heat stressors have exaggerated widespread effects on most organs ranging from structural alteration of the nervous system, increase coxygenase-2 on the vascular system and alteration of reproductive functions. While water immersion stress is peculiar with gastro intestinal system alteration proven to induce ulceration in experimental rats. Electric foot-shock and noise stress have more profound effects on the reproductive organs. Conclusion: Findings of this review showed that during experimental studies, restraint and heat stress have a wide range of effects on the body systems. While water immersion stress is the best used for gastrointestinal studies. Noise and electric foot-shock are maybe more relevant for reproductive stress induction.
... In fact, there is growing evidence reveals that chronic stress is a major risk factor for several human disorders, such as Alzheimer's disease and cognitive dysfunction, which is closely associated with the impairments of hippocapal neurogenesis, learning and memory, and emotional responses (McEwen, 2017;Lupien et al., 2018). Chronic restraint stress (CRS), as a typical model to simulate a living state of unpredictable setbacks in our daily life, also has ability to exacerbate neurodegeneration and impair cognitive function through inhibiting hippocampal neural activity, attenuating synaptic plasticity, and reducing neuronal cell survival (Anibal et al., 2017;Ngoupaye et al., 2017;Samarghandian et al., 2017). Available evidence shows that CRS causes the damage of hippocampal-dependent spatial learning and memory related to stress-caused synaptic dysfunction and oxidative damage, endoplasmic reticulum (ER) stress cascade and apoptosis in the hippocampal neurons (P. ...
Emerging evidence shows that chronic restraint stress (CRS) can induce cognitive dysfunction, which involves in hippocampal damage. Our recent research reveals that hydrogen sulfide (H2S), a novel gasotransmitter, protects against CRS-induced cognitive impairment, but the underlying mechanism remains unclear. Adiponectin, the most abundant plasma adipokine, has been shown to elicit neuroprotective property and attenuate cognitive impairment. Hence, the present work was aimed to explore whether adiponectin mediates the protective effect of H2S on CRS-induced cognitive impairment by inhibiting hippocampal damage. Results found that administration of Anti-Acrp30, a neutralizing antibody of adiponectin, obviously reverses sodium hydrosulfide (NaHS, an exogenous H2S donor)-induced the inhibition on CRS-induced cognitive impairment according to Y-maze test, Novel object recognition (NOR) test, and Morris water maze (MWM) test. In addition, Anti-Acrp30 blocked the protective effect of NaHS on hippocampal apoptosis in rats-subjected with CRS as evidenced by the pathological changes in hippocampus tissues in hematoxylin and eosin (HE) staining and the increases in the amount of the condensed and stained to yellowish-brown or brownish yellow neuron nucleuses in terminal deoxynucleotidyl transferase transfer-mediated dUTP nick end-labeling (TUNEL) staining as well as the expression of hippocampal pro-apoptotic protein (Bax), and a decrease in the expression of hippocampal anti-apoptotic protein (Bcl-2). Furthermore, Anti-Acrp30 mitigated the inhibitory effect of NaHS on CRS-induced oxidative stress as illustrated by the up-regulation of malondialdehyde (MDA) content and the down-regulation of superoxide dismutase (SOD) activity and glutathione (GSH) level in the hippocampus. Moreover, Anti-Acrp30 eliminated NaHS-induced the reduction of endoplasmic reticulum (ER) stress-related proteins including binding immunoglobulin protein (BIP), C/EBP homologous protein (CHOP), and Cleaved Caspase-12 expressions in the hippocampus of rats-exposed to CRS. Taken together, these results indicated that adiponectin mediates the protection of H2S against CRS-induced cognitive impairment through ameliorating hippocampal damage.
