Biomaterial Database

Endogenous hydrogen sulfide alleviates methotrexate-induced cognitive impairment by attenuating endoplasmic reticulum stress-induced apoptosis via CHOP and caspase-12. 2020

Siyuan Lv, and Ning Wu, and Qiang Wang, and Li-Hua Yang

Department of Neurosurgery, The National Key Clinic Specialty, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Engineering Technology Research Center of Education Ministry of China, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

The aim of this study was to estimate whether methotrexate (MTX) promotes cognitive impairment via increased ER stress and disrupted H2 S signaling in the hippocampus and whether H2 S may alleviate MTX-induced cognitive impairment by inhibiting ER stress through CHOP and caspase-12. Cognitive impairment behaviors were observed by Morris water maze test, and the apoptosis of neurons was assessed by TUNEL assay. The production of neurons was analyzed by DCX and Ki67 immunohistochemistry. The expressions of CHOP and caspase-12 in the hippocampus were determined by Western blot and immunohistochemistry. MTX increased the expression of CHOP and caspase-12 and the number of TUNEL-positive cells in the hippocampus by inhibiting endogenous H2 S-induced neuronal pyknosis in the hippocampal CA1 region. MTX decreased the number of DCX- and Ki67-positive cells in the hippocampal DG region. The results of Morris water maze showed that MTX could damage the spatial memory of rats. The changes of MTX-induced Morris water maze test in mice and H2 S levels in serum and hippocampus, as well as the expression of CHOP and caspase-12 and the number of CHOP and caspase-12-positive neurons in the hippocampus, indicated that H2 S could alleviate the cognitive impairment induced by methotrexate through CHOP and caspase-12.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008727	Methotrexate	An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.	Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D006862	Hydrogen Sulfide	A flammable, poisonous gas with a characteristic odor of rotten eggs. It is used in the manufacture of chemicals, in metallurgy, and as an analytical reagent. (From Merck Index, 11th ed)	Hydrogen Sulfide (H2(Sx)),Hydrogen Sulfide (H2S2),Hydrogen Sulfide (H2S3),Sulfide, Hydrogen
D000089662	Doublecortin Protein	A microtubule-associated protein that is primarily found in neuronal precursor cells and immature NEURONS in embryonic and adult cortical structures.	Lissencephaly, X-Linked Protein,Lissencephaly, X Linked Protein,X-Linked Protein Lissencephaly
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D017207	Rats, Sprague-Dawley	A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.	Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017209	Apoptosis	A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.	Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D051381	Rats	The common name for the genus Rattus.	Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D059865	Endoplasmic Reticulum Stress	Various physiological or molecular disturbances that impair ENDOPLASMIC RETICULUM function. It triggers many responses, including UNFOLDED PROTEIN RESPONSE, which may lead to APOPTOSIS; and AUTOPHAGY.	Stress, Endoplasmic Reticulum,Endoplasmic Reticulum Stresses,Reticulum Stress, Endoplasmic,Reticulum Stresses, Endoplasmic,Stresses, Endoplasmic Reticulum