PMID- 35578101 OWN - NLM STAT- MEDLINE DCOM- 20220608 LR - 20220608 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 59 IP - 7 DP - 2022 Jul TI - Rivastigmine Reverses the Decrease in Synapsin and Memory Caused by Homocysteine: Is There Relation to Inflammation? PG - 4517-4534 LID - 10.1007/s12035-022-02871-x [doi] AB - Elevated levels of homocysteine (Hcy) in the blood, called hyperhomocysteinemia (HHcy), is a prevalent risk factor for it has been shown that Hcy induces oxidative stress and increases microglial activation and neuroinflammation, as well as causes cognitive impairment, which have been linked to the neurodegenerative process. This study aimed to evaluate the effect of mild hyperhomocysteinemia with or without ibuprofen and rivastigmine treatments on the behavior and neurochemical parameters in male rats. The chronic mild HHcy model was chemically induced in Wistar rats by subcutaneous administration of Hcy (4055 mg/kg body weight) twice daily for 30 days. Ibuprofen (40 mg/kg) and rivastigmine (0.5 mg/kg) were administered intraperitoneally once daily. Motor damage (open field, balance beam, rotarod, and vertical pole test), cognitive deficits (Y-maze), neurochemical parameters (oxidative status/antioxidant enzymatic defenses, presynaptic protein synapsin 1, inflammatory profile parameters, calcium binding adapter molecule 1 (Iba1), iNOS gene expression), and cholinergic anti-inflammatory pathway were investigated. Results showed that mild HHcy caused cognitive deficits in working memory, and impaired motor coordination reduced the amount of synapsin 1 protein, altered the neuroinflammatory picture, and caused changes in the activity of catalase and acetylcholinesterase enzymes. Both rivastigmine and ibuprofen treatments were able to mitigate this damage caused by mild HHcy. Together, these neurochemical changes may be associated with the mechanisms by which Hcy has been linked to a risk factor for AD. Treatments with rivastigmine and ibuprofen can effectively reduce the damage caused by increased Hcy levels. CI - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Ramires Junior, Osmar Vieira AU - Ramires Junior OV AD - Laboratory of Neuroprotection and Neurometabolic Diseases - Wyse's Lab, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. AD - Post-Graduation Program of Biochemistry, Department of Biochemistry, Instituto de Ciencias Basicas da Saude, Universidade Federal Do Rio Grande Do Sul (UFRGS), Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. FAU - Dos Santos, Tiago Marcon AU - Dos Santos TM AD - Laboratory of Neuroprotection and Neurometabolic Diseases - Wyse's Lab, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. AD - Post-Graduation Program of Biochemistry, Department of Biochemistry, Instituto de Ciencias Basicas da Saude, Universidade Federal Do Rio Grande Do Sul (UFRGS), Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. FAU - Silveira, Josiane Silva AU - Silveira JS AD - Laboratory of Neuroprotection and Neurometabolic Diseases - Wyse's Lab, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. AD - Post-Graduation Program of Biochemistry, Department of Biochemistry, Instituto de Ciencias Basicas da Saude, Universidade Federal Do Rio Grande Do Sul (UFRGS), Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. FAU - Leite-Aguiar, Raissa AU - Leite-Aguiar R AD - Laboratory of Immunophysiology, Biophysics Institute Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. FAU - Coutinho-Silva, Robson AU - Coutinho-Silva R AD - Laboratory of Immunophysiology, Biophysics Institute Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. FAU - Savio, Luiz Eduardo Baggio AU - Savio LEB AD - Laboratory of Immunophysiology, Biophysics Institute Carlos Chagas Filho, Universidade Federal Do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil. FAU - Wyse, Angela T S AU - Wyse ATS AUID- ORCID: 0000-0001-8769-1147 AD - Laboratory of Neuroprotection and Neurometabolic Diseases - Wyse's Lab, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil. wyse@ufrgs.br. AD - Post-Graduation Program of Biochemistry, Department of Biochemistry, Instituto de Ciencias Basicas da Saude, Universidade Federal Do Rio Grande Do Sul (UFRGS), Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil. wyse@ufrgs.br. AD - Departamento de Bioquimica Instituto de Ciencias Basicas da Saude, Universidade Federal Do Rio Grande Do Sul (UFRGS), Rua Ramiro Barcelos, 2600-Anexo, RS, CEP 90035-003, Porto Alegre, Brazil. wyse@ufrgs.br. LA - eng GR - EN 465671/2014-4/Instituto Nacional de Ciencia e Tecnologia para Excitotoxicidade e Neuroprotecao/ GR - PRONEX 16/2551-0000465-0/Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul/ GR - E-26/202.701/2019/Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro/ GR - E-26/010.002422/2019/Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro/ GR - E-26/010.002260/2019/Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro/ PT - Journal Article DEP - 20220517 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (Synapsins) RN - 0LVT1QZ0BA (Homocysteine) RN - EC 3.1.1.7 (Acetylcholinesterase) RN - PKI06M3IW0 (Rivastigmine) RN - WK2XYI10QM (Ibuprofen) SB - IM MH - Acetylcholinesterase/metabolism MH - Animals MH - Homocysteine MH - *Hyperhomocysteinemia/chemically induced/complications/drug therapy MH - Ibuprofen MH - Inflammation/complications/drug therapy MH - Male MH - Oxidative Stress/physiology MH - Rats MH - Rats, Wistar MH - Rivastigmine/pharmacology/therapeutic use MH - Synapsins/metabolism OTO - NOTNLM OT - Cholinergic anti-inflammatory pathway OT - Homocysteine OT - Iba1 OT - Mild hyperhomocysteinemia OT - Neuroprotection OT - Synapsin 1 EDAT- 2022/05/17 06:00 MHDA- 2022/06/09 06:00 CRDT- 2022/05/16 23:32 PHST- 2021/09/01 00:00 [received] PHST- 2022/05/05 00:00 [accepted] PHST- 2022/05/17 06:00 [pubmed] PHST- 2022/06/09 06:00 [medline] PHST- 2022/05/16 23:32 [entrez] AID - 10.1007/s12035-022-02871-x [pii] AID - 10.1007/s12035-022-02871-x [doi] PST - ppublish SO - Mol Neurobiol. 2022 Jul;59(7):4517-4534. doi: 10.1007/s12035-022-02871-x. Epub 2022 May 17.