Riluzole prevents stress-induced spine plasticity in the hippocampus but mimics it in the amygdala

Naskar, Saptarnab; Datta, Siddhartha A.K.; Chattarji, Sumantra

doi:10.1016/j.ynstr.2022.100442

Cited by 11 publications

(16 citation statements)

References 75 publications

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“…Next, a separate cohort of animals were treated with riluzole for 24 hours in the drinking water, at a dosage that was previously shown to be effective in preventing the impact of stress in the rat hippocampus and PFC (31,33,36). Access to regular drinking water was resumed at the end of riluzole treatment (i.e., Day 1, Fig.1B).…”

Section: Resultsmentioning

confidence: 99%

“…A similar dosage of riluzole was used in previous studies involving the hippocampus and the PFC, (31,33,36), thereby providing a basis for comparing the findings in the BLA reported here. Interestingly, in addition to ALS, riluzole has also been used to treat psychiatric disorders (21,28,45,46).…”

Section: Discussionmentioning

confidence: 99%

“…This same treatment also prevented stress-induced alterations in glial metabolism in the PFC (31). Notably, those earlier analyses that used chronic stress paradigms, combined them with chronic riluzole treatments that overlapped with the entire duration of the chronic stress (31-33). In this context, it is interesting to note that the duration of riluzole treatment itself can give rise to strikingly different effects.…”

Section: Discussionmentioning

confidence: 99%

“…Further, riluzole is soluble in drinking water and hence bypasses the need for stressful interventions such as intraperitoneal injections or oral gavage in rodents (29,30). Interestingly, riluzole administered before or during chronic stress has been shown to block its effects in the hippocampus and prefrontal cortex (PFC) (31)(32)(33)(34). However, nothing is known about the efficacy of post-stress riluzole administration in preventing the delayed impact of acute stress in the amygdala.…”

Section: Introductionmentioning

confidence: 99%

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Administration of the glutamate-modulating drug riluzole after stress reverses its delayed effects on the amygdala

Datta

Rashid

Naskar

et al. 2023

Preprint

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Extracellular glutamate levels are elevated across brain regions immediately after stress. Despite sharing common features in their genesis, the patterns of stress-induced plasticity that eventually take shape are strikingly different between these brain areas. While stress impairs structure and function in the hippocampus, it has the opposite effect on the amygdala. Riluzole, an FDA-approved drug known to modulate glutamate release and facilitate glutamate clearance, prevents stress-induced deficits in the hippocampus. But, whether the same drug is also effective in countering the opposite effects of stress in the amygdala remains unexplored. We addressed this question by using a rat model wherein even a single 2-hour acute immobilization stress causes a delayed build-up, 10 days later, in anxiety-like behavior, alongside stronger excitatory synaptic connectivity in the basolateral amygdala (BLA). This temporal profile - several days separating the acute stressor and its delayed impact - allowed us to test if these effects can be reversed by administering riluzole in the drinking water after acute stress. Post-stress riluzole not only prevented the delayed increase in anxiety-like behavior on the elevated plus-maze, but also reversed the increase in spine-density on BLA neurons 10 days later. Further, stress-induced increase in the frequency of miniature excitatory postsynaptic currents recorded in BLA slices, 10 days later, was reversed by the same post-stress riluzole administration. Together, these findings underscore the importance of therapeutic strategies, aimed at glutamate uptake and modulation, in correcting the delayed behavioral, physiological, and morphological effects of stress on the amygdala.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Administration of the glutamate-modulating drug riluzole after stress reverses its delayed effects on the amygdala

Datta

Rashid

Naskar

et al. 2023

Preprint

Self Cite

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“…Treatment for depression has also been linked to changes in astrocytes. One study found that fluoxetine prevented psychosocial stress-induced reductions in the number of astrocytes [ 70 ], while another study found that riluzole can prevent the reduction in GFAP mRNA expression in the rat prefrontal cortex after exposure to CUS [ 71 ]. Citalopram and fluoxetine, two SSRI antidepressants, are thought to possess antidepressant effects because they can stimulate calcium signaling in astrocytes in the prefrontal cortex [ 72 ].…”

Section: Astrocyte and Depressionmentioning

confidence: 99%

A Review of Research on the Association between Neuron–Astrocyte Signaling Processes and Depressive Symptoms

Yao

Chen

Guo

et al. 2023

IJMS

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Depression is a mental illness that has a serious negative impact on physical and mental health. The pathophysiology of depression is still unknown, and therapeutic medications have drawbacks, such as poor effectiveness, strong dependence, adverse drug withdrawal symptoms, and harmful side effects. Therefore, the primary purpose of contemporary research is to understand the exact pathophysiology of depression. The connection between astrocytes, neurons, and their interactions with depression has recently become the focus of great research interest. This review summarizes the pathological changes of neurons and astrocytes, and their interactions in depression, including the alterations of mid-spiny neurons and pyramidal neurons, the alterations of astrocyte-related biomarkers, and the alterations of gliotransmitters between astrocytes and neurons. In addition to providing the subjects of this research and suggestions for the pathogenesis and treatment techniques of depression, the intention of this article is to more clearly identify links between neuronal–astrocyte signaling processes and depressive symptoms.

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497. Prefrontal Cortex Astroglia Modulate Anhedonia-Like Behavior

Codeluppi,

Xu,

Bansal

et al. 2024

Biological Psychiatry

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Riluzole prevents stress-induced spine plasticity in the hippocampus but mimics it in the amygdala

Cited by 11 publications

References 75 publications

Administration of the glutamate-modulating drug riluzole after stress reverses its delayed effects on the amygdala

Administration of the glutamate-modulating drug riluzole after stress reverses its delayed effects on the amygdala

A Review of Research on the Association between Neuron–Astrocyte Signaling Processes and Depressive Symptoms

497. Prefrontal Cortex Astroglia Modulate Anhedonia-Like Behavior

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