‘Hot spots’ of creatine kinase localization in brain: cerebellum, hippocampus and choroid plexus
Abstract
Creatine kinase (CK) isoenzymes, with emphasis on the mitochondrial CK isoenzymes, were characterized and localized in chicken cerebellum. Chicken cerebellum extracts analyzed by two-dimensional gels, using antipeptide antibodies specific for sarcomeric muscle-type mitochondrial CK (Mib-CK) and revealed the presence of a Mib-CK variant in avian cerebellum. This CK isoform was localized by immunofluorescence staining exclusively in the Purkinje neurons. The co-expression of this Mib-CK together with cytosolic muscle-type MM-CK, as observed in the same Purkinje neurons, may reflect the specific energy requirements associated with highly fluctuating Ca2+ levels (Ca2+ spiking) in these specialized neurons. Ubiquitous brain-type mitochondrial Mia-CK was found together with cytosolic BB-CK mainly in the glomeruli structures of the cerebellar granular layer. BB-CK, but much less so Mia-CK however, was also very prominent in Bergmann glial cells of the two mitochondrial Mi-CK isoenzymes in the chicken cerebellum is demonstrated. Other hot spots of CK localization were the granule and pyramidal cells of the hippocampus in rat. There, a developmental stage-dependent immunofluorescence staining, especially with antibodies against Mia-CK was noted. Epithelial cells of the choroid plexus were also highly enriched in CK. The possible implications of a CK/PCr circuit at these various cellular locations of the brain are discussed with respect to normal brain physiology and pathology.
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Creatine-deficient syndromes that deplete brain creatine stores are characterized by mental and developmental disorders such as learning delays and seizures, and these symptoms can be partially reversed by creatine supplementation.
“As an example of the importance of creatine in humans, creatine-deficient syndromes that deplete brain creatine stores are characterized by mental and developmental disorders such as learning delays and seizures17,18; importantly, these symptoms can be partially reversed by creatine supplementation.19–21”
From Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [19]
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“Interestingly, CK-B localization is particularly abundant in highly plastic brain regions implicated in learning and memory, including the hippocampus and cerebellum (Kaldis et al. 1996).”
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“Although we detected that all neurons colocalized with BB-CK and uMt-CK in our spinal cord cultures, previous reports have shown that CKs are also present in oligodendrocytes and astrocytes (Molloy et al., 1992; Kaldis et al., 1996; Andres et al., 2005b).”
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“Previous studies have described some energy demanding events in neuronal and glial cells in the brain which begin during early postnatal development and which may either require or be accelerated by Cy-CK [50, 52].”
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“Muscle-type CK isoform in Purkinje neurons was discussed with respect to the unique fluctuating Ca2+ metabolism (Hemmer et al., 1994; Kaldis et al., 1996).”
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“Two types of CK, cytosolic brain-type creatine kinase and ubiquitous CK-mit, are expressed in the mammalian brain and are found in abundance in the HIP region [41].”
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“Muscle creatine kinase (CKM) is also expressed in neurons (Hamburg et al. 1990; Hemmer et al. 1994; Kaldis et al. 1996) and a low level of CKM immunoreactivity in the spiral ganglion neurons and inner hair cells in the adult mouse and gerbil cochleae was found (Spicer and Schulte 1992).”
BackgroundMatton, A., Axenhus, M., Bogdanović, N., Winblad, B. G., Schedin‐Weiss, S., Nilsson, P., & Tjernberg, L. O. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.735334 · Cited by 8 · see citing works
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Proteomics Reveals Intersexual Differences in the Rat Brain Hippocampus
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“CKB is expressed in a variety of tissues, and is most abundant in adult brains where most CKB has been shown to be cytosolic (Urdal et al., 1983; Mitchell and Benfield, 1990; Manos et al., 1991; Friedman and Roberts, 1994; Kaldis et al., 1996; Shen et al., 2002).”
BackgroundMR Spectroscopy in Health and Disease
Öz, G. (2012) · Springer eBooks · doi:10.1007/978-94-007-1333-8_29 · Cited by 7 · see citing works
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“The higher concentration of total creatine in cerebellum than in cerebrum is consistent with the high activity and labeling of specific creatine kinase isoforms in Purkinje cells and Bergmann glia in developing cerebellum (Holtzman et al., 1993; Kaldis et al., 1996).”
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“Hippocampus is known to be important for learning and memory, it is there that the greatest disturbances at Alzheimer’s disease were revealed [3, 42 ].”
Background4.2 Mitochondrial Architecture and Heterogeneity
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“…between neurons and glia Enzyme Difference between neurons and glia References Creatine kinase Purkinje neurons, but not glia of cerebellum Kaldis et al. (1996) Cytochrome oxidase Lower activity in glia Tolani and Talwar (1963); Difiglia et al. (1987); Wong‐Riley (1989) Glutamate…”
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da Silva, C. G., Bueno, A. R. F., Rosa, R. B., Dutra‐Filho, C. S., Wannmacher, C. M. D., Wyse, Â. T. D. S., & Wajner, M. (2003) · Neurochemical Research · doi:10.1023/a:1024936129908 · Cited by 5 · see citing works
“We cannot establish at the present time the reason for these results, but they may be due to distinct isoforms of the enzyme in various brain structures (35).”
Creatine monohydrate for mitochondrial nutrition
Kamel, M. A. E.-N., Moussa, Y. Y., & Gowayed, M. A. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90256-4.00004-7 · Cited by 4 · see citing works
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“Notably, the cerebellum is a “hot spot” of CK localization in the CNS [61], underscoring the pivotal role of these enzymes in normal cerebellar function.”
BackgroundCreatine kinase/α-crystallin interaction functions in cataract development
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Mitochondrial Approaches to Neuroprotection
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“The creatine kinase/phosphocreatine shuttle functions both as a subcellular energy transport system and as a temporal energy buffer [14].”
Supplementation of creatine and its role in brain function
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Proton Magnetic Resonance Spectroscopy for Dementia
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Creatine Kinase as Biomarker in Osteogenesis Imperfecta
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“The ubiquitous brain-type cytosolic isoform (CKbb) is found primarily in the brain and retina where it is associated with ion transport pumps in the brain (Kaldis et al. 1996).”
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КРЕАТИН ЯК ХІМІЧНА РЕЧОВИНА, ЙОГО ФУНКЦІЇ В ОРГАНІЗМІ ТА РОЛЬ У СПОРТІ
Токарик, Г., Кос, Л., Туник, А., Chubiy, I. Z., & Shkurashivska, S. V. (2024) · Перспективи та інновації науки · doi:10.52058/2786-4952-2024-8(42)-1173-1186
- Authors
- Kaldis, P., Hemmer, W., Zanolla, E., Holtzman, D., & Wallimann, T.
- Affiliations
- ETH Zurich (CH)
- Venue
- Developmental Neuroscience
- Publisher
- S. Karger AG
- Published
- 2009-08-24
- Volume
- 18
- Issue
- 5-6
- Pages
- 542-554
- ISSN
- 0378-5866 (ISSN-L)
- 1421-9859
- OpenAlex
- W2051168961
- Cited by
- 99
- References
- 0
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 1 · 2022: 4 · 2021: 8 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 1 · 2014: 3 · 2013: 5 · 2012: 6
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Developmental Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Chengdu University of Information Technology
- National Institutes of Health (5r01ns026371-07)
- National Institute for Materials Science
- National Institute of Neurological Disorders and Stroke (NS-26371)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- creatine kinase, creatine kinase isoenzymes, mitochondrial creatine kinase, Purkinje cells, Bergmann glia, cerebellar granular layer, hippocampus, choroid plexus, phosphocreatine, brain energy metabolism, calcium spikes, developmental gene expression
- MeSH terms
- Animals, Cerebellum, Chickens, Choroid Plexus, Creatine Kinase, Fluorescent Antibody Technique, Hippocampus, Isoenzymes, Microscopy, Fluorescence, Mitochondria, Tissue Distribution, Electrophoresis, Gel, Two-Dimensional, Rats
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