Increased levels and activity of cathepsins B and D in kainate-induced toxicity

Banerjee, Minakshi; Sasse, V.A.; Wang, Y.; Maulik, Mahua; Kar, Satyabrata

doi:10.1016/j.neuroscience.2014.10.003

Cited by 17 publications

(11 citation statements)

References 80 publications

(150 reference statements)

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“…In keeping with earlier studies , we observed that systemic administration of kainic acid evoked seizures characterized by rearing and falling, facial and forelimb clonus, and “wet‐dog” shakes that lasted about 8–10 h. After a seizure‐free period lasting a few days, a high proportion of animals surviving such an attack exhibited a chronic phase of spontaneous recurrent limbic seizures with no remission over 12 days of the experimental paradigm . These behavioral changes are accompanied by a loss of neurons, as apparent by Fluoro‐Jade C and cleaved caspase‐3‐labeling, as well as glial hypertrophy in the hippocampus of the rat brain (Figure A–K).…”

Section: Resultssupporting

confidence: 88%

“…These behavioral changes are accompanied by a loss of neurons, as apparent by Fluoro‐Jade C and cleaved caspase‐3‐labeling, as well as glial hypertrophy in the hippocampus of the rat brain (Figure A–K). As expected, reduced neuronal viability progressed with time primarily in CA1‐CA3 pyramidal cells and the hilar region of the dentate gyrus, whereas the granule cell layer was relatively spared . The hypertrophy of astrocytes and microglia (data not shown) was apparent to some extent at 12 h and then gradually increased over 12 days post‐treatment period (Figure A–I).…”

Section: Resultssupporting

confidence: 64%

“…The experiments were performed in accordance with Institutional and Canadian Council on Animal Care guidelines. Adult rats were injected intraperitoneally with either kainic acid dissolved in normal saline (12 mg/kg) or equal volume (0.2–0.25 mL) normal saline as described previously . Following treatment, the control and kainic acid‐treated rats were euthanized at 12 h, 2, and 12 days by decapitation; their hippocampi were dissected out of the brain and frozen immediately in dry‐ice for biochemical assays.…”

Section: Methodsmentioning

confidence: 99%

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A role for astrocyte‐derived amyloid β peptides in the degeneration of neurons in an animal model of temporal lobe epilepsy

Kodam¹,

Ourdev²,

Maulik

et al. 2018

Brain Pathology

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Kainic acid, an analogue of the excitatory neurotransmitter glutamate, can trigger seizures and neurotoxicity in the hippocampus and other limbic structures in a manner that mirrors the neuropathology of human temporal lobe epilepsy (TLE). However, the underlying mechanisms associated with the neurotoxicity remain unclear. Since amyloid-β (Aβ) peptides, which are critical in the development of Alzheimer's disease, can mediate toxicity by activating glutamatergic NMDA receptors, it is likely that the enhanced glutamatergic transmission that renders hippocampal neurons vulnerable to kainic acid treatment may involve Aβ peptides. Thus, we seek to establish what role Aβ plays in kainic acid-induced toxicity using in vivo and in vitro paradigms. Our results show that systemic injection of kainic acid to adult rats triggers seizures, gliosis and loss of hippocampal neurons, along with increased levels/processing of amyloid precursor protein (APP), resulting in the enhanced production of Aβ-related peptides. The changes in APP levels/processing were evident primarily in activated astrocytes, implying a role for astrocytic Aβ in kainic acid-induced toxicity. Accordingly, we showed that treating rat primary cultured astrocytes with kainic acid can lead to increased Aβ production/secretion without any compromise in cell viability. Additionally, we revealed that kainic acid reduces neuronal viability more in neuronal/astrocyte co-cultures than in pure neuronal culture, and this is attenuated by precluding Aβ production. Collectively, these results indicate that increased production/secretion of Aβ-related peptides from activated astrocytes can contribute to neurotoxicity in kainic acid-treated rats. Since kainic acid administration can lead to neuropathological changes resembling TLE, it is likely that APP/Aβ peptides derived from astrocytes may have a role in TLE pathogenesis.

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Section: Resultssupporting

confidence: 88%

Section: Resultssupporting

confidence: 64%

Section: Methodsmentioning

confidence: 99%

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A role for astrocyte‐derived amyloid β peptides in the degeneration of neurons in an animal model of temporal lobe epilepsy

Kodam¹,

Ourdev²,

Maulik

et al. 2018

Brain Pathology

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“…On the other hand, although the role of CTSB in the brain is controversial, inhibition of CTSB in transient ischemia is known to prevent nerve cell death [17]. CTSB is also considered to be involved in the early phase of protease and Alzheimer's disease including cell apoptosis after brain injury [18]. From another view, however, CTSB has been reported to have neuroprotective [19] with anti-amyloidogenic properties [20].…”

Section: Discussionmentioning

confidence: 99%

Brain function factors after high acceleration exposure in Korea Air Force cadets

Bae¹,

Ok²,

Park³

et al. 2018

biomedicalresearch

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Fighter pilots perform a variety of physical activities to improve and maintain their fitness, but there is a lack of research on brain function factors for high acceleration exposure. Therefore, the aim of this study was to investigate the differences of physical fitness between success and failure group, and to examine the changes in blood brain function factors after exposure to high acceleration condition. Air force cadets were participated and divided into the success (n=38), failure within 10 s (failure group A, n=19), failure within 20 s (failure group B, n=10) and failure within 30 s (failure group C, n=12) groups after conducting G-tolerance test. In terms of muscle mass, the failure group C showed significantly higher values than the failure group A (p<0.05). In the sit-up test, the success group showed significantly higher values than the failure group D (p<0.05). BDNF and CTSB levels were significantly increased in the success group and the failure group D after acceleration exposure (p<0.05). As can be seen from the results of this study, high acceleration exposure caused a significant increase in the CTSB level in the success group that is considered to be the result of high strength isometric movement of the human body to withstand high pressure. Therefore, the results of this study suggested that to improve muscle strength is essential to withstand high acceleration conditions.

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“…In addition to modulation of specific microglial cell surface receptors, seizures also upregulated microglial cytokine expression including TGFβ (Morgan et al, ), IL‐1β (Eriksson et al, ; Vezzani et al, ), and TNF‐α (Turrin and Rivest, ). Finally, regarding microglial proteases, cathepsin B, D, and S were increased following seizures (Akahoshi et al, ; Banerjee et al, ). Together, these studies highlight the dramatic upregulation of microglial receptors, cytokines, and proteases following seizures.…”

Section: Microglial Morphological and Molecular Activation In Responsmentioning

confidence: 99%

Microglia–Neuron Communication in Epilepsy

Eyo

Murugan

2016

Glia

214

196

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Epilepsy has remained a significant social concern and financial burden globally. Current therapeutic strategies are based primarily on neurocentric mechanisms that have not proven successful in at least a third of patients, raising the need for novel alternative and complementary approaches. Recent evidence implicates glial cells and neuroinflammation in pathogenesis of epilepsy with the promise of targeting these cells to complement existing strategies. Specifically, microglial involvement, as a major inflammatory cell in the epileptic brain, has been poorly studied. In this review, we highlight microglial reaction to experimental seizures, discuss microglial control of neuronal activities, and propose the functions of microglia during acute epileptic phenotypes, delayed neurodegeneration and aberrant neurogenesis. Future research that would help fill in the current gaps in our knowledge including epilepsy-induced alterations in basic microglial functions, neuro-microglial interactions during chronic epilepsy, and microglial contributions to developmental seizures. Studying the role of microglia in epilepsy could inform therapies to better alleviate the disease.

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Increased levels and activity of cathepsins B and D in kainate-induced toxicity

Cited by 17 publications

References 80 publications

A role for astrocyte‐derived amyloid β peptides in the degeneration of neurons in an animal model of temporal lobe epilepsy

A role for astrocyte‐derived amyloid β peptides in the degeneration of neurons in an animal model of temporal lobe epilepsy

Brain function factors after high acceleration exposure in Korea Air Force cadets

Microglia–Neuron Communication in Epilepsy

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