Article
Neurosciences
Anton N. Shuvaev, Olga S. Belozor, Oleg Mozhei, Dariya A. Yakovleva, Ilya V. Potapenko, Andrey N. Shuvaev, Marina V. Smolnikova, Vladimir V. Salmin, Alla B. Salmina, Hirokazu Hirai, Anja G. Teschemacher, Sergey Kasparov
Summary: In cerebellar neurodegenerative diseases such as SCA1, reactive BG can negatively impact neuronal function and survival through compromised glutamate uptake. Excessive glutamate signaling appears to be a common feature in SCA1 pathology, contributing to cerebellar neurodegeneration.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Cell Biology
Anton N. Shuvaev, Olga S. Belozor, Oleg Mozhei, Andrey N. Shuvaev, Yana Fritsler, Elena D. Khilazheva, Angelina Mosyagina, Hirokazu Hirai, Anja G. Teschemacher, Sergey Kasparov
Summary: Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by mutant ATXN1 protein accumulation, leading to deficits in motor performance and synaptic plasticity. The disease affects both neurons and glial cells.
Article
Multidisciplinary Sciences
Kimberly Luttik, Leon Tejwani, Hyoungseok Ju, Terri Driessen, Cleo J. L. M. Smeets, Chandrakanth Reddy Edamakanti, Aryaan Khan, Joy Yun, Puneet Opal, Janghoo Lim
Summary: Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease characterized by progressive ataxia and degeneration of specific neuronal populations. This study found that the Wnt-beta-catenin signaling pathway is progressively enhanced in the adult SCA1 mouse cerebellum and is activated in an ataxin-1 polyglutamine (polyQ) expansion-dependent manner. Activation of this pathway in astrocytes led to gliosis and disrupted Bergmann glia (BG) localization, replicating SCA1-like phenotypes in mouse models. These findings highlight the important role of BG in SCA1 pathogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Immunology
Chandrakanth Reddy Edamakanti, Vishwa Mohan, Puneet Opal
Summary: Using human SCA autopsy samples, researchers discovered inflammatory JNK-dependent c-Jun phosphorylation in Bergmann glia, and inhibiting the JNK pathway reduced Bergmann glia inflammation and improved the SCA1 phenotype both behaviorally and pathologically, suggesting a causal role for Bergmann glia inflammation in SCA1 and a potential therapeutic strategy.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Neurosciences
Carmen Nanclares, Jose Antonio Noriega-Prieto, Francisco E. Labrada-Moncada, Marija Cvetanovic, Alfonso Araque, Paulo Kofuji
Summary: Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease characterized by progressive cerebellar ataxia. This study found that the intrinsic electrical properties of Purkinje cells (PCs) in SCA1 mice were altered, and these alterations were associated with the hyperexcitability of Bergmann glia (BG). Preventing BG hyperexcitability in SCA1 mice restored the normal function of PCs.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Neurosciences
Vanessa L. Hull, Yan Wang, Travis Burns, Sarah Sternbach, Shuaishuai Gong, Jennifer McDonough, Fuzheng Guo, Laura N. Borodinsky, David Pleasure
Summary: Canavan disease is a pediatric leukodystrophy caused by mutations in the ASPA gene, resulting in a deficiency of the enzyme aspartoacylase. This leads to increased levels of N-acetyl-L-aspartate (NAA) in the brain and various neurological symptoms. In a mouse model of Canavan disease, researchers found that Bergmann glia (BG) exhibited significant morphological alterations and dysfunction, which preceded cerebellar degeneration. However, treatment with an antisense oligonucleotide targeting Nat8l, which reduces NAA production, was able to repair the BG and improve motor function. This suggests that restoring BG integrity may be a potential therapeutic strategy for Canavan disease.
Article
Neurosciences
Ella Borgenheimer, Katherine Hamel, Carrie Sheeler, Francisco Labrada Moncada, Kaelin Sbrocco, Ying Zhang, Marija Cvetanovic
Summary: In the early stages of SCA1 in mice, there were no changes in the proportions of neurons and glial cells in the cerebellum, but Bergmann glia, velate astrocytes, and oligodendrocytes showed profound non-cell autonomous and potentially neuroprotective reactive gene and pathway alterations in response to Purkinje cell dysfunction.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Shelanah Salih, Zubair Ahmed Nizamudeen, Nigel De Melo, Lisa Chakrabarti, Virginie Sottile
Summary: Recent observations suggest that Bergmann glia in the cerebellum may play a role in tissue repair due to their expression of neural stem cell markers, although the physiological relevance of this overlap remains unclear in the absence of established in vivo evidence of tissue regeneration in the adult cerebellum.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mohamed A. Elsaey, Kazuhiko Namikawa, Reinhard W. Koester
Summary: A zebrafish model of SCA1 has been developed to study PC degeneration patterns and behavioral changes, which may provide insights into disease mechanisms and potential therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Won-Seok Lee, Laura Lavery, Maxime W. C. Rousseaux, Eric B. Rutledge, Youjin Jang, Ying-Wooi Wan, Sih-Rong Wu, Wonho Kim, Ismael Al-Ramahi, Smruti Rath, Carolyn J. Adamski, Vitaliy V. Bondar, Ambika Tewari, Shirin Soleimani, Samantha Mota, Hari K. Yalamanchili, Harry T. Orr, Zhandong Liu, Juan Botas, Huda Y. Zoghbi
Summary: The selective vulnerability of specific brain regions in SCA1 is regulated by region-specific regulators of ATXN1, and targeting multiple regulators has the potential to rescue multiple degenerating brain areas.
Review
Biochemistry & Molecular Biology
Victor Olmos, Neha Gogia, Kimberly Luttik, Fatema Haidery, Janghoo Lim
Summary: SCA1 is a late-onset, progressive, dominantly inherited genetic disease characterized by the loss of Purkinje cells in the cerebellum and motor deficits. In addition to these symptoms, there are also extra-cerebellar effects such as respiratory problems, cognitive defects, memory impairment, anxiety, and depression. The existing gap in research on extra-cerebellar regions in SCA1 highlights the need for further investigation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Neurosciences
Shahin Shabanipour, Xiaodan Jiao, Maryam Rahimi-Balaei, Mohamad Reza Aghanoori, Seung H. Chung, Saeid Ghavami, G. Giacomo Consalez, Hassan Marzban
Summary: This study investigates the role of NCAM1 in the development of Purkinje cells (PCs). The results suggest that NCAM1 expression is significantly upregulated when PCs fail to align and instead overmigrate into the molecular layer. This may indicate that NCAM1 plays a crucial role in the migration process of PCs.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Martina Sucha, Simona Benediktova, Filip Tichanek, Jan Jedlicka, Stepan Kapl, Dana Jelinkova, Zdenka Purkartova, Jan Tuma, Jitka Kuncova, Jan Cendelin
Summary: This study aimed to explore the potential of edaravone to slow down SCA1 progression in a mouse knock-in SCA1 model. However, the results showed that edaravone did not have any plausible therapeutic effect on either behavioral dysfunctions or other disease hallmarks in SCA1 mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Vasiliki Tellios, Matthew J. E. Maksoud, Wei-Yang Lu
Summary: This study is the first to characterize BG morphology and GLAST expression during development in nNOS(-/-) mice using immunohistochemistry and western blotting. The results showed that BG in nNOS(-/-) mice exhibited abnormal morphology and decreased GLAST expression compared with wildtype (WT) mice across postnatal development. It was also found that nNOS/NO signaling regulates BG development through a PKG-mediated mechanism.
Article
Neurosciences
Takahiro Fujimoto, Kirsten Stam, Takeshi Yaoi, Kenta Nakano, Tetsuya Arai, Tadashi Okamura, Kyoko Itoh
Summary: This study aimed to investigate the expression profile of Dp71 in the cerebellum and found its presence in glial cells, Bergmann glial cells, and astrocytes, while Dp427 was exclusively expressed in inhibitory postsynapses within cerebellar Purkinje cells. Additionally, the study revealed biochemical associations of Dp71 with AQP4 and Kir4.1 in both the cerebellum and cerebrum, and partial co-localization of Dp71 with AQP4 and Kir4.1 in glial cells. The results suggest that different cell types in the cerebellum express different dystrophin molecular complexes, which may play a role in pathological and physiological processes through the regulation of water/ion channels and inhibitory postsynapses.
MOLECULAR NEUROBIOLOGY
(2023)