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Modeling cerebellar limb dysmetria and impaired spatial memory in rats using lamivudine: A preliminary study.
J Chem Neuroanat. 2020 Jun 20; 109:101838.JC

Abstract

BACKGROUND AND AIM

Neurodegeneration has been associated with the use of combination antiretroviral therapy (cART). This study is aimed at determining if any constituent of cART can induce cerebellar limb dysmetria and spatial memory impairments.

MATERIALS AND METHODS

Forty adult male Wistar rats were randomly grouped into four (n = 10): control (distilled water 0.5 mL); Tenofovir (6 mg/kg); Lamivudine (6 mg/kg) and Efavirenz (12 mg/kg). The following neurobehavioral studies were conducted: open field, beam walk, and Morris water maze. Immunohistochemistry of CD 68 and GFAP were used to test for neuroinflammation and neurodegeneration.

RESULTS

There was marked increase in pyknotic pyramidal cells of the hippocampus and ghost Purkinje cells in the cerebellum of treatment groups. There was also a significant increase in oxidative stress in lamivudine and efavirenz groups. In addition, Lamivudine caused a significant increase of microglial and astrocytic activity (p < 0.001, 0.05 respectively) compared to control. The open field test showed a significant decrease (p < 0.0001) of the line crossing performance in the efavirenz, lamivudine and tenofovir (with means: 26.4, 4.6, 17.4 respectively) compared to control (50.6). There was also a significant decrease in the grooming (p < 0.05) and rearing (p < 0.01) in lamivudine group. Whereas, walk latency increased in efavirenz (p < 0.01), and lamivudine (p < 0.0001) compared to control. While hind limb slips significantly increased in efavirenz (p < 0.05) and lamivudine (p < 0.0001) compared with control group. Likewise, Lamivudine and Tenofovir exposed groups experienced a significant delay in the time to identify the hidden platform in compared to control (p < 0.05).

CONCLUSION

Lamivudine altered efferent stimuli along the cerebellospinal tracts thereby causing motor impairments. The degenerating Purkinje fibers may have induced marked neurodegeneration in the hippocampus resulting in impaired spatial memory.

Authors+Show Affiliations

Department of Anatomy, College of Medicine, University of Lagos, P.M.B. 12003, Idi-Araba, Lagos, Nigeria. Electronic address: enakang@cmul.edu.ng.Department of Anatomy, College of Medicine, University of Lagos, P.M.B. 12003, Idi-Araba, Lagos, Nigeria. Electronic address: odosumu@unilag.edu.ng.Department of Anatomy, College of Medicine, University of Lagos, P.M.B. 12003, Idi-Araba, Lagos, Nigeria. Electronic address: samcode039@gmail.com.Department of Anatomy, College of Medicine, University of Lagos, P.M.B. 12003, Idi-Araba, Lagos, Nigeria. Electronic address: joannnenna24@gmail.com.Department of Haematology and Blood Transfusion, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria. Electronic address: asakanmu@cmul.edu.ng.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32569723

Citation

Akang, Edidiong, et al. "Modeling Cerebellar Limb Dysmetria and Impaired Spatial Memory in Rats Using Lamivudine: a Preliminary Study." Journal of Chemical Neuroanatomy, vol. 109, 2020, p. 101838.
Akang E, Dosumu O, Afolayan S, et al. Modeling cerebellar limb dysmetria and impaired spatial memory in rats using lamivudine: A preliminary study. J Chem Neuroanat. 2020;109:101838.
Akang, E., Dosumu, O., Afolayan, S., Agumah, R., & Akanmu, A. S. (2020). Modeling cerebellar limb dysmetria and impaired spatial memory in rats using lamivudine: A preliminary study. Journal of Chemical Neuroanatomy, 109, 101838. https://doi.org/10.1016/j.jchemneu.2020.101838
Akang E, et al. Modeling Cerebellar Limb Dysmetria and Impaired Spatial Memory in Rats Using Lamivudine: a Preliminary Study. J Chem Neuroanat. 2020 Jun 20;109:101838. PubMed PMID: 32569723.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modeling cerebellar limb dysmetria and impaired spatial memory in rats using lamivudine: A preliminary study. AU - Akang,Edidiong, AU - Dosumu,Olufunke, AU - Afolayan,Samuel, AU - Agumah,Rhoda, AU - Akanmu,Alani Sulaimon, Y1 - 2020/06/20/ PY - 2020/03/12/received PY - 2020/05/25/revised PY - 2020/06/10/accepted PY - 2020/6/23/pubmed PY - 2020/6/23/medline PY - 2020/6/23/entrez KW - Antiretrovirals KW - Astrocytes KW - Ataxia KW - Cognition KW - Memory KW - Microglia KW - Movement disorders SP - 101838 EP - 101838 JF - Journal of chemical neuroanatomy JO - J. Chem. Neuroanat. VL - 109 N2 - BACKGROUND AND AIM: Neurodegeneration has been associated with the use of combination antiretroviral therapy (cART). This study is aimed at determining if any constituent of cART can induce cerebellar limb dysmetria and spatial memory impairments. MATERIALS AND METHODS: Forty adult male Wistar rats were randomly grouped into four (n = 10): control (distilled water 0.5 mL); Tenofovir (6 mg/kg); Lamivudine (6 mg/kg) and Efavirenz (12 mg/kg). The following neurobehavioral studies were conducted: open field, beam walk, and Morris water maze. Immunohistochemistry of CD 68 and GFAP were used to test for neuroinflammation and neurodegeneration. RESULTS: There was marked increase in pyknotic pyramidal cells of the hippocampus and ghost Purkinje cells in the cerebellum of treatment groups. There was also a significant increase in oxidative stress in lamivudine and efavirenz groups. In addition, Lamivudine caused a significant increase of microglial and astrocytic activity (p < 0.001, 0.05 respectively) compared to control. The open field test showed a significant decrease (p < 0.0001) of the line crossing performance in the efavirenz, lamivudine and tenofovir (with means: 26.4, 4.6, 17.4 respectively) compared to control (50.6). There was also a significant decrease in the grooming (p < 0.05) and rearing (p < 0.01) in lamivudine group. Whereas, walk latency increased in efavirenz (p < 0.01), and lamivudine (p < 0.0001) compared to control. While hind limb slips significantly increased in efavirenz (p < 0.05) and lamivudine (p < 0.0001) compared with control group. Likewise, Lamivudine and Tenofovir exposed groups experienced a significant delay in the time to identify the hidden platform in compared to control (p < 0.05). CONCLUSION: Lamivudine altered efferent stimuli along the cerebellospinal tracts thereby causing motor impairments. The degenerating Purkinje fibers may have induced marked neurodegeneration in the hippocampus resulting in impaired spatial memory. SN - 1873-6300 UR - https://www.unboundmedicine.com/medline/citation/32569723/Modeling_cerebellar_limb_dysmetria_and_impaired_spatial_memory_in_rats_using_lamivudine:_A_preliminary_study L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-0618(20)30107-1 DB - PRIME DP - Unbound Medicine ER -
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