Cognitive Decline and Mood Alterations in the Mouse Model of Spinocerebellar Ataxia Type 2

Marinina, Ksenia S.; Bezprozvanny, Ilya; Egorova, Polina A.

doi:10.1007/s12311-023-01520-w

Cited by 4 publications

(2 citation statements)

References 57 publications

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“…There are several paradigms of FC testing [90,91]. Here, we used an auditory one because it corresponds well with changes observed in the downstream of Alzheimer's disease and other neurodegenerative diseases [92,93]. We used optogenetics to evaluate the positive effect of hippocampal astrocytic OPTO-α1AR activation that was expressed in the increase in the context and cued freezing time.…”

Section: Discussionmentioning

confidence: 99%

“…The mice were given four consecutive training days with four trials per day in which they could find the platform hidden in the SE quadrant under muddy water. To find the hidden platform of search, the animals should navigate by four black-and-white signs located in four intercardiac directions at a height of 0.10 m above the water surface [ 93 ]. The mice began their 90 s swim in four different cardinal directions, which were randomly assigned.…”

Section: Methodsmentioning

confidence: 99%

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Activation of Gq-Coupled Receptors in Astrocytes Restores Cognitive Function in Alzheimer’s Disease Mice Model

Gerasimov

Bezprozvanny

Власова

2023

IJMS

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Alzheimer’s disease (AD) is one of the most widespread neurodegenerative diseases. Most of the current AD therapeutic developments are directed towards improving neuronal cell function or facilitating Aβ amyloid clearance from the brain. However, some recent evidence suggests that astrocytes may play a significant role in the pathogenesis of AD. In this paper, we evaluated the effects of the optogenetic activation of Gq-coupled exogenous receptors expressed in astrocytes as a possible way of restoring brain function in the AD mouse model. We evaluated the effects of the optogenetic activation of astrocytes on long-term potentiation, spinal morphology and behavioral readouts in 5xFAD mouse model of AD. We determined that in vivo chronic activation of astrocytes resulted in the preservation of spine density, increased mushroom spine survival, and improved performance in cognitive behavioral tests. Furthermore, chronic optogenetic stimulation of astrocytes resulted in the elevation of EAAT-2 glutamate uptake transporter expression, which could be a possible explanation for the observed in vivo neuroprotective effects. The obtained results suggest that the persistent activation of astrocytes may be considered a potential therapeutic approach for the treatment of AD and possibly other neurodegenerative disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Activation of Gq-Coupled Receptors in Astrocytes Restores Cognitive Function in Alzheimer’s Disease Mice Model

Gerasimov

Bezprozvanny

Власова

2023

IJMS

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A chlorzoxazone–folic acid combination improves cognitive affective decline in SCA2-58Q mice

Marinina

Bezprozvanny

Egorova

2023

Sci Rep

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Spinocerebellar ataxia type 2 (SCA2) is a polyglutamine disorder caused by a pathological expansion of CAG repeats in ATXN2 gene. SCA2 is accompanied by cerebellar degeneration and progressive motor decline. Cerebellar Purkinje cells (PCs) seem to be primarily affected in this disorder. The majority of the ataxia research is focused on the motor decline observed in ataxic patients and animal models of the disease. However, recent evidence from patients and ataxic mice suggests that SCA2 can also share the symptoms of the cerebellar cognitive affective syndrome. We previously reported that SCA2-58Q PC-specific transgenic mice exhibit anxiolytic behavior, decline in spatial memory, and a depressive-like state. Here we studied the effect of the activation of the small conductance calcium-activated potassium channels (SK channels) by chlorzoxazone (CHZ) combined with the folic acid (FA) on the PC firing and also motor, cognitive and affective symptoms in SCA2-58Q mice. We realized that CHZ-FA combination improved motor and cognitive decline as well as ameliorated mood alterations in SCA2-58Q mice without affecting the firing rate of their cerebellar PCs. Our results support the idea of the combination therapy for both ataxia and non-motor symptoms in ataxic mice without affecting the firing frequency of PCs.

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Memory decline, anxiety and depression in the mouse model of spinocerebellar ataxia type 3

Marinina,

Bezprozvanny,

Egorova

2023

Human Molecular Genetics

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Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant hereditary disorder, caused by an expansion of polyglutamine in the ataxin-3 protein. SCA3 symptoms include progressive motor decline caused by an atrophy of the cerebellum and brainstem. However, it was recently reported that SCA3 patients also suffer from the cerebellar cognitive affective syndrome. The majority of SCA3 patients exhibit cognitive decline and approximately half of them suffer from depression and anxiety. The necessity to find a combined therapy for both motor and cognitive deficits in a SCA3 mouse model is required for the development of SCA3 treatment. Here, we demonstrated that the SCA3-84Q transgenic mice exhibited anxiety over the novel brightly illuminated environment in the open field, novelty suppressed feeding, and light–dark place preference tests. Moreover, SCA3-84Q mice also suffered from a decline in recognition memory during the novel object recognition test. SCA3-84Q mice also demonstrated floating behavior during the Morris water maze that can be interpreted as a sign of low mood and aversion to activity, i. e. depressive-like state. SCA3-84Q mice also spent more time immobile during the forced swimming and tail suspension tests which is also evidence for depressive-like behavior. Therefore, the SCA3-84Q mouse model may be used as a model system to test the possible treatments for both ataxia and non-motor symptoms including depression, anxiety, and memory loss.

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Cognitive Decline and Mood Alterations in the Mouse Model of Spinocerebellar Ataxia Type 2

Cited by 4 publications

References 57 publications

Activation of Gq-Coupled Receptors in Astrocytes Restores Cognitive Function in Alzheimer’s Disease Mice Model

Activation of Gq-Coupled Receptors in Astrocytes Restores Cognitive Function in Alzheimer’s Disease Mice Model

A chlorzoxazone–folic acid combination improves cognitive affective decline in SCA2-58Q mice

Memory decline, anxiety and depression in the mouse model of spinocerebellar ataxia type 3

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