Abnormalities in the cerebellar levels of trophic factors BDNF and GDNF in pcd and lurcher cerebellar mutant mice

Šalomová, Martina; Tichánek, Filip; Jelı́nková, Dana; Cendelín, Jan

doi:10.1016/j.neulet.2020.134870

Cited by 12 publications

(5 citation statements)

References 35 publications

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“…Concerning the neuroprotective factors, a downregulation in Bdnf gene expression was observed in PCD mice as compared to age-matched WT animals (Figure 7). This is in line with previous work reporting decreased Bdnf levels/expression in a broad spectrum of neurological diseases, including PCD mice but at a much older age [56]. The specific cause of this downregulation is unclear; however, it is known that proinflammatory cytokines, especially IL1β, can cause downregulation of Bdnf expression [57].…”

Section: Discussionsupporting

confidence: 91%

Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration

Pérez-Martín,

Pérez-Revuelta,

Barahona-López

et al. 2023

IJMS

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Neurodegenerative diseases involve an exacerbated neuroinflammatory response led by microglia that triggers cytokine storm and leukocyte infiltration into the brain. PPARα agonists partially dampen this neuroinflammation in some models of brain insult, but neuronal loss was not the triggering cause in any of them. This study examines the anti-inflammatory and immunomodulatory properties of the PPARα agonist oleoylethanolamide (OEA) in the Purkinje Cell Degeneration (PCD) mouse, which exhibits striking neuroinflammation caused by aggressive loss of cerebellar Purkinje neurons. Using real-time quantitative polymerase chain reaction and immunostaining, we quantified changes in pro- and anti-inflammatory markers, microglial density and marker-based phenotype, and overall leukocyte recruitment at different time points after OEA administration. OEA was found to modulate cerebellar neuroinflammation by increasing the gene expression of proinflammatory mediators at the onset of neurodegeneration and decreasing it over time. OEA also enhanced the expression of anti-inflammatory and neuroprotective factors and the Pparα gene. Regarding microgliosis, OEA reduced microglial density—especially in regions where it is preferentially located in PCD mice—and shifted the microglial phenotype towards an anti-inflammatory state. Finally, OEA prevented massive leukocyte infiltration into the cerebellum. Overall, our findings suggest that OEA may change the environment to protect neurons from degeneration caused by exacerbated inflammation.

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Section: Discussionsupporting

confidence: 91%

Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration

Pérez-Martín,

Pérez-Revuelta,

Barahona-López

et al. 2023

IJMS

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“…Hippocampal BDNF level. The hippocampal BDNF levels were determined as described previously 72 , employing the BDNF SimpleStep commercial enzyme-linked immunosorbent assay (ELISA) kit (ab212166, Abcam) and used according to the manufacturer's instructions. The data were normalized to the protein content measured via the use of a BCA1 kit (B9643; Sigma-Aldrich, Saint Louis, USA).…”

Section: Methodsmentioning

confidence: 99%

Hippocampal mitochondrial dysfunction and psychiatric-relevant behavioral deficits in spinocerebellar ataxia 1 mouse model

Tichánek

Šalomová

Jedlička

et al. 2020

Sci Rep

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Spinocerebellar ataxia 1 (SCA1) is a devastating neurodegenerative disease associated with cerebellar degeneration and motor deficits. However, many patients also exhibit neuropsychiatric impairments such as depression and apathy; nevertheless, the existence of a causal link between the psychiatric symptoms and SCA1 neuropathology remains controversial. This study aimed to explore behavioral deficits in a knock-in mouse SCA1 (SCA1 154Q/2Q) model and to identify the underlying neuropathology. We found that the SCA1 mice exhibit previously undescribed behavioral impairments such as increased anxiety-and depressive-like behavior and reduced prepulse inhibition and cognitive flexibility. Surprisingly, non-motor deficits characterize the early SCA1 stage in mice better than does ataxia. Moreover, the SCA1 mice exhibit significant hippocampal atrophy with decreased plasticity-related markers and markedly impaired neurogenesis. Interestingly, the hippocampal atrophy commences earlier than the cerebellar degeneration and directly reflects the individual severity of some of the behavioral deficits. Finally, mitochondrial respirometry suggests profound mitochondrial dysfunction in the hippocampus, but not in the cerebellum of the young SCA1 mice. These findings imply the essential role of hippocampal impairments, associated with profound mitochondrial dysfunction, in SCA1 behavioral deficits. Moreover, they underline the view of SCA1 as a complex neurodegenerative disease and suggest new avenues in the search for novel SCA1 therapies. Spinocerebellar ataxia type 1 (SCA1) is a lethal dominantly-inherited neurodegenerative disease, caused by CAG repeat expansion (> 40 CAG repeats) in the ataxin-1 encoding gene (ATXN1) 1. This mutation results in ataxin-1 protein toxicity and aggregation which leads, in particular, to cerebellar and brainstem degeneration 2 , although ATXN1 is widely expressed throughout the brain 1. SCA1 symptoms usually appear in early middle-age and include motor incoordination and gait deficits followed by muscular and swallowing problems in the later stages of the disease 3. However, in a similar way to other types of spinocerebellar ataxias (SCAs), over 50% of patients also demonstrate neuropsychiatric issues 4-7 including cognitive impairments, anxiety, apathy and depression 7-9. Interestingly, in contrast to progressive ataxia, the psychiatric impairments tend to remain relatively stable over time 8. Although they are often overlooked, they profoundly impact the quality of life and health outcomes of patients with SCA1 and related diseases 9. However, the question of whether these psychiatric impairments are causally linked to SCA1 neuropathology, or if they represent an emotional response to SCA1 diagnosis and subsequent physical disability, remains controversial 9 .

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“…The cerebellum is responsible for coordination and fine regulation of movement, and its dysfunction can cause motor ataxia. BDNF is highly expressed in cerebellar granule cells and Purkinje cells, and BDNF deficiency can result in abnormality of morphology of the cells, especially their synapses (Carter et al, 2002;Salomova et al, 2020). In BDNF knockout mice, migration of cerebellar granule cells is impaired, and is relieved after administration of exogenous BDNF (Borghesani et al, 2002).…”

Section: Brain-derived Neurotrophic Factor and The Cerebellar Ataxiamentioning

confidence: 99%

The Role of Brain-Derived Neurotrophic Factor Signaling in Central Nervous System Disease Pathogenesis

Dou

Cui

Huang

et al. 2022

Front. Hum. Neurosci.

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Recent studies have found abnormal levels of brain-derived neurotrophic factor (BDNF) in a variety of central nervous system (CNS) diseases (e.g., stroke, depression, anxiety, Alzheimer’s disease, and Parkinson’s disease). This suggests that BDNF may be involved in the pathogenesis of these diseases. Moreover, regulating BDNF signaling may represent a potential treatment for such diseases. With reference to recent research papers in related fields, this article reviews the production and regulation of BDNF in CNS and the role of BDNF signaling disorders in these diseases. A brief introduction of the clinical application status of BDNF is also provided.

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Abnormalities in the cerebellar levels of trophic factors BDNF and GDNF in pcd and lurcher cerebellar mutant mice

Cited by 12 publications

References 35 publications

Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration

Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration

Hippocampal mitochondrial dysfunction and psychiatric-relevant behavioral deficits in spinocerebellar ataxia 1 mouse model

The Role of Brain-Derived Neurotrophic Factor Signaling in Central Nervous System Disease Pathogenesis

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