Abstract
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.
Highlights
Pertaining to stress, it is an obvious prevalent experience that a large number of individuals are facing different levels of chronic stress in life (Cohen et al, 2016; Yaribeygi et al, 2017)
Our results found that neutralizing adiponectin by Anti-Acrp30 reverses the protection of H2S against chronic restraint stress (CRS)-induced cognitive impairment
Anti-Acrp30 abolishes the inhibitory effect of H2S on hippocampal apoptosis, oxidative stress, and endoplasmic reticulum (ER) stress in the CRS-exposed rats, indicating that neutralizing adiponectin blocks H2S-induced the attenuation of hippocampal impairment in CRS-exposed rats
Summary
Pertaining to stress, it is an obvious prevalent experience that a large number of individuals are facing different levels of chronic stress in life (Cohen et al, 2016; Yaribeygi et al, 2017). 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, 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 It is urgent and essential to find the therapeutic regimens of hippocampal damage and cognitive impairment induced by CRS, which is beneficial to improve human health
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