Electrophysiological and molecular changes following neuroprotective placental protein administration on tinnitus‐induced rats

Mohammad Farhadi; Ali Gorji; Marjan Mirsalehi; Alexander Borisovich Poletaev; Abdoreza Asadpour; Fereidoun Mahboudi; Maryam Jafarian; Maryam Farrahizadeh; Zeinab Akbarnejad; Saeid Mahmoudian

doi:10.1002/lio2.1156

Electrophysiological and molecular changes following neuroprotective placental protein administration on tinnitus‐induced rats

Mohammad Farhadi, Ali Gorji, Marjan Mirsalehi, Alexander Borisovich Poletaev, Abdoreza Asadpour, Fereidoun Mahboudi, Maryam Jafarian, Maryam Farrahizadeh, Zeinab Akbarnejad, Saeid Mahmoudian

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Abstract

Objective: Despite 6%–20% of the adult population suffering from tinnitus, there is no standard treatment for it. Placenta extract has been used for various therapeutic purposes, including hearing loss. Here, we evaluate the effect of a novel neuroprotective protein composition (NPPC) extract on electrophysiological and molecular changes in the medial geniculate body (MGB) of tinnitus‐induced rats. Methods: To evaluate the protein analysis by western blot, the rats were divided into three groups: (1) saline group (intraperitoneal injection of 200 mg/kg saline twice a day for 28 consecutive days, (2) chronic Na‐Sal group received sodium salicylate as in the first group, and (3) chronic treatment group (received salicylate 200 mg/kg twice daily for 2 weeks, followed by 0.4 mg NPPC daily from day 14 to day 28). Single‐unit recordings were performed on a separate group that was treated as in group 4. Gap‐prepulse inhibition of the acoustic startle (GPIAS) and pre‐pulse inhibition (PPI) was performed to confirm tinnitus in all groups at the baseline, 14th and 28th days. Results: Western blot analysis showed that the expression of γ‐Aminobutyric acid Aα1 subunit (GABA Aα1), N‐methyl‐d‐aspartate receptor subtype 2B (NR2B or NMDAR2B), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors subunit GluR1 (GluR1), and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors subunit GluR2 (GluR2) decreased after Na‐Sal injection, while NPPC upregulated their expression. MGB units in rats with tinnitus showed decreased spontaneous firing rate, burst per minute, and a spike in a burst. After NPPC administration, neural activity patterns showed a significant positive effect of NPPC on tinnitus. Conclusion: NPPC can play an effective role in the treatment of tinnitus in salicylate‐induced rats, and MGB is one of the brain areas involved in these processes. Level of Evidence: NA.

Original language	English
Pages (from-to)	1410-1420
Number of pages	11
Journal	Laryngoscope Investigative Otolaryngology
Volume	8
Issue number	5
Early online date	3 Oct 2023
DOIs	https://doi.org/10.1002/lio2.1156
Publication status	Published online - 3 Oct 2023

Bibliographical note

Funding Information:
The generous support of the Iran National Science Foundation (INSF), as well as ENT and Head & Neck Research Center, Iran University of Medical Sciences to assign credit to the research line auditory neuroscience, is gratefully acknowledged. Also, all authors would like to appreciate the late Professor Alexander Borisovich Poletaev (*06 November 1951—† March 6th, 2021). He was the first to report the evident positive effects of the protein fraction of porcine placental extract introduced by Alexander Anikin, in terms of having prominent neuroprotective properties, initially named X‐proteins (XP). He also generously provided the placenta extract extraction method to this research group. The authors further thank all colleagues as well as administrative personnel at Shefa Neuroscience Institute, Tehran, Iran, who contributed to data collection.

Funding Information:
This study was financially supported by the Iran National Science Foundation (INSF, Synergy Grant Code no. insf‐98020383‐1400/03/23 and 95830795), and ENT and Head and Neck Research Center, Hazrate Rasoul Akram Hospital, the Five Senses Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran (Ethical approval no. IR.IUMS.REC.1398.233).

Publisher Copyright:
© 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.

Funding

Funding Information: The generous support of the Iran National Science Foundation (INSF), as well as ENT and Head & Neck Research Center, Iran University of Medical Sciences to assign credit to the research line auditory neuroscience, is gratefully acknowledged. Also, all authors would like to appreciate the late Professor Alexander Borisovich Poletaev (*06 November 1951—† March 6th, 2021). He was the first to report the evident positive effects of the protein fraction of porcine placental extract introduced by Alexander Anikin, in terms of having prominent neuroprotective properties, initially named X‐proteins (XP). He also generously provided the placenta extract extraction method to this research group. The authors further thank all colleagues as well as administrative personnel at Shefa Neuroscience Institute, Tehran, Iran, who contributed to data collection. Funding Information: This study was financially supported by the Iran National Science Foundation (INSF, Synergy Grant Code no. insf‐98020383‐1400/03/23 and 95830795), and ENT and Head and Neck Research Center, Hazrate Rasoul Akram Hospital, the Five Senses Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran (Ethical approval no. IR.IUMS.REC.1398.233). Publisher Copyright: © 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.

Keywords

startle reflex
tinnitus
placenta extract
single unit recording
sodium salicylate

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Farhadi, M., Gorji, A., Mirsalehi, M., Poletaev, A. B., Asadpour, A., Mahboudi, F., Jafarian, M., Farrahizadeh, M., Akbarnejad, Z., & Mahmoudian, S. (2023). Electrophysiological and molecular changes following neuroprotective placental protein administration on tinnitus‐induced rats. Laryngoscope Investigative Otolaryngology, 8(5), 1410-1420. Advance online publication. https://doi.org/10.1002/lio2.1156

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abstract = "Objective: Despite 6\%–20\% of the adult population suffering from tinnitus, there is no standard treatment for it. Placenta extract has been used for various therapeutic purposes, including hearing loss. Here, we evaluate the effect of a novel neuroprotective protein composition (NPPC) extract on electrophysiological and molecular changes in the medial geniculate body (MGB) of tinnitus‐induced rats. Methods: To evaluate the protein analysis by western blot, the rats were divided into three groups: (1) saline group (intraperitoneal injection of 200 mg/kg saline twice a day for 28 consecutive days, (2) chronic Na‐Sal group received sodium salicylate as in the first group, and (3) chronic treatment group (received salicylate 200 mg/kg twice daily for 2 weeks, followed by 0.4 mg NPPC daily from day 14 to day 28). Single‐unit recordings were performed on a separate group that was treated as in group 4. Gap‐prepulse inhibition of the acoustic startle (GPIAS) and pre‐pulse inhibition (PPI) was performed to confirm tinnitus in all groups at the baseline, 14th and 28th days. Results: Western blot analysis showed that the expression of γ‐Aminobutyric acid Aα1 subunit (GABA Aα1), N‐methyl‐d‐aspartate receptor subtype 2B (NR2B or NMDAR2B), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors subunit GluR1 (GluR1), and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors subunit GluR2 (GluR2) decreased after Na‐Sal injection, while NPPC upregulated their expression. MGB units in rats with tinnitus showed decreased spontaneous firing rate, burst per minute, and a spike in a burst. After NPPC administration, neural activity patterns showed a significant positive effect of NPPC on tinnitus. Conclusion: NPPC can play an effective role in the treatment of tinnitus in salicylate‐induced rats, and MGB is one of the brain areas involved in these processes. Level of Evidence: NA.",

keywords = "startle reflex, tinnitus, placenta extract, single unit recording, sodium salicylate",

author = "Mohammad Farhadi and Ali Gorji and Marjan Mirsalehi and Poletaev, \{Alexander Borisovich\} and Abdoreza Asadpour and Fereidoun Mahboudi and Maryam Jafarian and Maryam Farrahizadeh and Zeinab Akbarnejad and Saeid Mahmoudian",

note = "Funding Information: The generous support of the Iran National Science Foundation (INSF), as well as ENT and Head \& Neck Research Center, Iran University of Medical Sciences to assign credit to the research line auditory neuroscience, is gratefully acknowledged. Also, all authors would like to appreciate the late Professor Alexander Borisovich Poletaev (*06 November 1951—† March 6th, 2021). He was the first to report the evident positive effects of the protein fraction of porcine placental extract introduced by Alexander Anikin, in terms of having prominent neuroprotective properties, initially named X‐proteins (XP). He also generously provided the placenta extract extraction method to this research group. The authors further thank all colleagues as well as administrative personnel at Shefa Neuroscience Institute, Tehran, Iran, who contributed to data collection. Funding Information: This study was financially supported by the Iran National Science Foundation (INSF, Synergy Grant Code no. insf‐98020383‐1400/03/23 and 95830795), and ENT and Head and Neck Research Center, Hazrate Rasoul Akram Hospital, the Five Senses Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran (Ethical approval no. IR.IUMS.REC.1398.233). Publisher Copyright: {\textcopyright} 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.",

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doi = "10.1002/lio2.1156",

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Farhadi, M, Gorji, A, Mirsalehi, M, Poletaev, AB, Asadpour, A, Mahboudi, F, Jafarian, M, Farrahizadeh, M, Akbarnejad, Z & Mahmoudian, S 2023, 'Electrophysiological and molecular changes following neuroprotective placental protein administration on tinnitus‐induced rats', Laryngoscope Investigative Otolaryngology, vol. 8, no. 5, pp. 1410-1420. https://doi.org/10.1002/lio2.1156

TY - JOUR

T1 - Electrophysiological and molecular changes following neuroprotective placental protein administration on tinnitus‐induced rats

AU - Farhadi, Mohammad

AU - Gorji, Ali

AU - Mirsalehi, Marjan

AU - Poletaev, Alexander Borisovich

AU - Asadpour, Abdoreza

AU - Mahboudi, Fereidoun

AU - Jafarian, Maryam

AU - Farrahizadeh, Maryam

AU - Akbarnejad, Zeinab

AU - Mahmoudian, Saeid

N1 - Funding Information: The generous support of the Iran National Science Foundation (INSF), as well as ENT and Head & Neck Research Center, Iran University of Medical Sciences to assign credit to the research line auditory neuroscience, is gratefully acknowledged. Also, all authors would like to appreciate the late Professor Alexander Borisovich Poletaev (*06 November 1951—† March 6th, 2021). He was the first to report the evident positive effects of the protein fraction of porcine placental extract introduced by Alexander Anikin, in terms of having prominent neuroprotective properties, initially named X‐proteins (XP). He also generously provided the placenta extract extraction method to this research group. The authors further thank all colleagues as well as administrative personnel at Shefa Neuroscience Institute, Tehran, Iran, who contributed to data collection. Funding Information: This study was financially supported by the Iran National Science Foundation (INSF, Synergy Grant Code no. insf‐98020383‐1400/03/23 and 95830795), and ENT and Head and Neck Research Center, Hazrate Rasoul Akram Hospital, the Five Senses Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran (Ethical approval no. IR.IUMS.REC.1398.233). Publisher Copyright: © 2023 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.

PY - 2023/10/3

Y1 - 2023/10/3

N2 - Objective: Despite 6%–20% of the adult population suffering from tinnitus, there is no standard treatment for it. Placenta extract has been used for various therapeutic purposes, including hearing loss. Here, we evaluate the effect of a novel neuroprotective protein composition (NPPC) extract on electrophysiological and molecular changes in the medial geniculate body (MGB) of tinnitus‐induced rats. Methods: To evaluate the protein analysis by western blot, the rats were divided into three groups: (1) saline group (intraperitoneal injection of 200 mg/kg saline twice a day for 28 consecutive days, (2) chronic Na‐Sal group received sodium salicylate as in the first group, and (3) chronic treatment group (received salicylate 200 mg/kg twice daily for 2 weeks, followed by 0.4 mg NPPC daily from day 14 to day 28). Single‐unit recordings were performed on a separate group that was treated as in group 4. Gap‐prepulse inhibition of the acoustic startle (GPIAS) and pre‐pulse inhibition (PPI) was performed to confirm tinnitus in all groups at the baseline, 14th and 28th days. Results: Western blot analysis showed that the expression of γ‐Aminobutyric acid Aα1 subunit (GABA Aα1), N‐methyl‐d‐aspartate receptor subtype 2B (NR2B or NMDAR2B), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors subunit GluR1 (GluR1), and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors subunit GluR2 (GluR2) decreased after Na‐Sal injection, while NPPC upregulated their expression. MGB units in rats with tinnitus showed decreased spontaneous firing rate, burst per minute, and a spike in a burst. After NPPC administration, neural activity patterns showed a significant positive effect of NPPC on tinnitus. Conclusion: NPPC can play an effective role in the treatment of tinnitus in salicylate‐induced rats, and MGB is one of the brain areas involved in these processes. Level of Evidence: NA.

AB - Objective: Despite 6%–20% of the adult population suffering from tinnitus, there is no standard treatment for it. Placenta extract has been used for various therapeutic purposes, including hearing loss. Here, we evaluate the effect of a novel neuroprotective protein composition (NPPC) extract on electrophysiological and molecular changes in the medial geniculate body (MGB) of tinnitus‐induced rats. Methods: To evaluate the protein analysis by western blot, the rats were divided into three groups: (1) saline group (intraperitoneal injection of 200 mg/kg saline twice a day for 28 consecutive days, (2) chronic Na‐Sal group received sodium salicylate as in the first group, and (3) chronic treatment group (received salicylate 200 mg/kg twice daily for 2 weeks, followed by 0.4 mg NPPC daily from day 14 to day 28). Single‐unit recordings were performed on a separate group that was treated as in group 4. Gap‐prepulse inhibition of the acoustic startle (GPIAS) and pre‐pulse inhibition (PPI) was performed to confirm tinnitus in all groups at the baseline, 14th and 28th days. Results: Western blot analysis showed that the expression of γ‐Aminobutyric acid Aα1 subunit (GABA Aα1), N‐methyl‐d‐aspartate receptor subtype 2B (NR2B or NMDAR2B), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors subunit GluR1 (GluR1), and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors subunit GluR2 (GluR2) decreased after Na‐Sal injection, while NPPC upregulated their expression. MGB units in rats with tinnitus showed decreased spontaneous firing rate, burst per minute, and a spike in a burst. After NPPC administration, neural activity patterns showed a significant positive effect of NPPC on tinnitus. Conclusion: NPPC can play an effective role in the treatment of tinnitus in salicylate‐induced rats, and MGB is one of the brain areas involved in these processes. Level of Evidence: NA.

KW - startle reflex

KW - tinnitus

KW - placenta extract

KW - single unit recording

KW - sodium salicylate

UR - https://www.scopus.com/pages/publications/85173442290

U2 - 10.1002/lio2.1156

DO - 10.1002/lio2.1156

M3 - Article

C2 - 37899856

SN - 2378-8038

VL - 8

SP - 1410

EP - 1420

JO - Laryngoscope Investigative Otolaryngology

JF - Laryngoscope Investigative Otolaryngology

IS - 5

ER -

Electrophysiological and molecular changes following neuroprotective placental protein administration on tinnitus‐induced rats

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