Lack of Parkinsonian Pathology and Neurodegeneration in Mice After Long-Term Injections of a Proteasome Inhibitor in Olfactory Bulb and Amygdala
Proteinaceous inclusions, called Lewy bodies (LBs), are used as a pathological hallmark for Parkinson’s disease (PD). Recent studies suggested a prion-like spreading mechanism for α-synucleinopathy where early neuropathological deposits occur, among others, in the olfactory bulb (OB) and amygdala. L...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2021.698979/full |
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| author | Natalia Lopez-Gonzalez del Rey Natalia Lopez-Gonzalez del Rey Natalia Lopez-Gonzalez del Rey Tiziano Balzano Tiziano Balzano Lucia Martin-Rodriguez Constanza Salinas-Rebolledo Ines Trigo-Damas Ines Trigo-Damas Alejandro Rojas-Fernandez Lydia Alvarez-Erviti Javier Blesa Javier Blesa |
| author_facet | Natalia Lopez-Gonzalez del Rey Natalia Lopez-Gonzalez del Rey Natalia Lopez-Gonzalez del Rey Tiziano Balzano Tiziano Balzano Lucia Martin-Rodriguez Constanza Salinas-Rebolledo Ines Trigo-Damas Ines Trigo-Damas Alejandro Rojas-Fernandez Lydia Alvarez-Erviti Javier Blesa Javier Blesa |
| author_sort | Natalia Lopez-Gonzalez del Rey |
| collection | DOAJ |
| description | Proteinaceous inclusions, called Lewy bodies (LBs), are used as a pathological hallmark for Parkinson’s disease (PD). Recent studies suggested a prion-like spreading mechanism for α-synucleinopathy where early neuropathological deposits occur, among others, in the olfactory bulb (OB) and amygdala. LBs contain insoluble α-synuclein and many other ubiquitinated proteins, suggesting a role of protein degradation system failure in PD pathogenesis. Therefore, we wanted to study the effects of a proteasomal inhibitor, lactacystin, on the aggregability and transmissibility of α-synuclein in the OB and amygdala. We performed injections of lactacystin in the OB and amygdala of wild-type mice. Motor behavior, markers of neuroinflammation, α-synuclein, and dopaminergic integrity were assessed by immunohistochemistry. Overall, there were no differences in the number of neurons and α-synuclein expression in these regions following injection of lactacystin into either the OB or amygdala. Microglial and astroglial labeling appeared to be correlated with surgery-induced inflammation or local effects of lactacystin. Consistent with the behavior and pathological findings, there was no loss of dopaminergic cell bodies in the substantia nigra and terminals in the striatum. Our data showed that long-term lactacystin injections in extra nigrostriatal regions may not mimic spreading aspects of PD and reinforce the special vulnerability of dopaminergic neurons of the substantia nigra pars compacta (SNc). |
| first_indexed | 2024-12-18T02:31:12Z |
| format | Article |
| id | doaj.art-fe641d89c91c452282b4e7d41804d29b |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-18T02:31:12Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-fe641d89c91c452282b4e7d41804d29b2022-12-21T21:23:53ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-10-011310.3389/fnagi.2021.698979698979Lack of Parkinsonian Pathology and Neurodegeneration in Mice After Long-Term Injections of a Proteasome Inhibitor in Olfactory Bulb and AmygdalaNatalia Lopez-Gonzalez del Rey0Natalia Lopez-Gonzalez del Rey1Natalia Lopez-Gonzalez del Rey2Tiziano Balzano3Tiziano Balzano4Lucia Martin-Rodriguez5Constanza Salinas-Rebolledo6Ines Trigo-Damas7Ines Trigo-Damas8Alejandro Rojas-Fernandez9Lydia Alvarez-Erviti10Javier Blesa11Javier Blesa12HM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, SpainCentro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainPhD Program in Neuroscience, Autonoma de Madrid University-Cajal Institute, Madrid, SpainHM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, SpainCentro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainHM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, SpainFaculty of Medicine, Institute of Medicine, Universidad Austral de Chile, Valdivia, ChileHM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, SpainCentro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainFaculty of Medicine, Institute of Medicine, Universidad Austral de Chile, Valdivia, ChileLaboratory of Molecular Neurobiology, Center for Biomedical Research of La Rioja (CIBIR), Logroño, SpainHM CINAC (Centro Integral de Neurociencias Abarca Campal), Hospital Universitario HM Puerta del Sur, HM Hospitales, Madrid, SpainCentro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, SpainProteinaceous inclusions, called Lewy bodies (LBs), are used as a pathological hallmark for Parkinson’s disease (PD). Recent studies suggested a prion-like spreading mechanism for α-synucleinopathy where early neuropathological deposits occur, among others, in the olfactory bulb (OB) and amygdala. LBs contain insoluble α-synuclein and many other ubiquitinated proteins, suggesting a role of protein degradation system failure in PD pathogenesis. Therefore, we wanted to study the effects of a proteasomal inhibitor, lactacystin, on the aggregability and transmissibility of α-synuclein in the OB and amygdala. We performed injections of lactacystin in the OB and amygdala of wild-type mice. Motor behavior, markers of neuroinflammation, α-synuclein, and dopaminergic integrity were assessed by immunohistochemistry. Overall, there were no differences in the number of neurons and α-synuclein expression in these regions following injection of lactacystin into either the OB or amygdala. Microglial and astroglial labeling appeared to be correlated with surgery-induced inflammation or local effects of lactacystin. Consistent with the behavior and pathological findings, there was no loss of dopaminergic cell bodies in the substantia nigra and terminals in the striatum. Our data showed that long-term lactacystin injections in extra nigrostriatal regions may not mimic spreading aspects of PD and reinforce the special vulnerability of dopaminergic neurons of the substantia nigra pars compacta (SNc).https://www.frontiersin.org/articles/10.3389/fnagi.2021.698979/fullParkinson’s diseaseproteasome inhibitionlactacystinneuroinflammationneurodegeneration |
| spellingShingle | Natalia Lopez-Gonzalez del Rey Natalia Lopez-Gonzalez del Rey Natalia Lopez-Gonzalez del Rey Tiziano Balzano Tiziano Balzano Lucia Martin-Rodriguez Constanza Salinas-Rebolledo Ines Trigo-Damas Ines Trigo-Damas Alejandro Rojas-Fernandez Lydia Alvarez-Erviti Javier Blesa Javier Blesa Lack of Parkinsonian Pathology and Neurodegeneration in Mice After Long-Term Injections of a Proteasome Inhibitor in Olfactory Bulb and Amygdala Frontiers in Aging Neuroscience Parkinson’s disease proteasome inhibition lactacystin neuroinflammation neurodegeneration |
| title | Lack of Parkinsonian Pathology and Neurodegeneration in Mice After Long-Term Injections of a Proteasome Inhibitor in Olfactory Bulb and Amygdala |
| title_full | Lack of Parkinsonian Pathology and Neurodegeneration in Mice After Long-Term Injections of a Proteasome Inhibitor in Olfactory Bulb and Amygdala |
| title_fullStr | Lack of Parkinsonian Pathology and Neurodegeneration in Mice After Long-Term Injections of a Proteasome Inhibitor in Olfactory Bulb and Amygdala |
| title_full_unstemmed | Lack of Parkinsonian Pathology and Neurodegeneration in Mice After Long-Term Injections of a Proteasome Inhibitor in Olfactory Bulb and Amygdala |
| title_short | Lack of Parkinsonian Pathology and Neurodegeneration in Mice After Long-Term Injections of a Proteasome Inhibitor in Olfactory Bulb and Amygdala |
| title_sort | lack of parkinsonian pathology and neurodegeneration in mice after long term injections of a proteasome inhibitor in olfactory bulb and amygdala |
| topic | Parkinson’s disease proteasome inhibition lactacystin neuroinflammation neurodegeneration |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2021.698979/full |
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