Depression comorbidity in epileptic rats is related to brain glucose hypometabolism and hypersynchronicity in the metabolic network architecture

Zanirati, Gabriele; Azevedo, Pâmella Nunes; Venturin, Gianina Teribele; Greggio, Samuel; Alcará, Allan Marinho; Zimmer, Eduardo R.; Feltes, Paula Kopschina; Costa, Jaderson Costa da

doi:10.1111/epi.14057

Cited by 27 publications

(24 citation statements)

References 42 publications

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“…Thus, our results suggest that following epilepsy manifestation, hippocampal hypometabolism may constitute a marker of neurobehavioral alterations, as opposed to a marker of seizure severity. A recent study in the chemically induced pilocarpine post‐SE model has similarly described a correlation between reduced [ 18 F]FDG uptake and a depressivelike phenotype . The authors reported a global reduction in [ 18 F]FDG uptake as opposed to the region‐specific reduction indicated by our results.…”

Section: Discussionsupporting

confidence: 62%

Imaging biomarkers of behavioral impairments: A pilot micro–positron emission tomographic study in a rat electrical post–status epilepticus model

et al. 2018

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Objective:In patients with epilepsy, psychiatric comorbidities can significantly affect the disease course and quality of life. Detecting and recognizing these comorbidities is central in determining an optimal treatment plan. One promising tool in detecting biomarkers for psychiatric comorbidities in epilepsy is positron emission tomography (PET). Methods: Behavioral and biochemical variables were cross-correlated with the results from two μPET scans using the tracers [ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG) and 2′-methoxyphenyl-(N-2′-pyridinyl)-p-18 F-fluoro-benzamidoethylpiperazine ([ 18 F]MPPF) to explore potential biomarkers for neurobehavioral comorbidities in an electrically induced post-status epilepticus rat model of epilepsy.Results: In rats with epilepsy, μPET analysis revealed a local reduction in hippocampal [ 18 F]FDG uptake, and a local increase in [ 18 F]MPPF binding. These changes exhibited a correlation with burrowing as a "luxury" behavior, social interaction, and anxiety-associated behavioral patterns. Interestingly, hippocampal [ 18 F]FDG uptake did not correlate with spontaneous recurrent seizure activity. Significance: In the electrically induced post-status epilepticus rat model, we demonstrated hippocampal hypometabolism and its correlation with a range of neurobehavioral alterations. These findings require further confirmation in other preclinical models and patients with epilepsy and psychiatric disorders to address the value of [ 18 F]FDG uptake as an imaging biomarker candidate for psychiatric comorbidities in patients as well as for severity assessment in rodent epilepsy models.

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Section: Discussionsupporting

confidence: 62%

Imaging biomarkers of behavioral impairments: A pilot micro–positron emission tomographic study in a rat electrical post–status epilepticus model

et al. 2018

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“…With this protocol, we activate not only cortical zones but also inner structures that are essential in cognitive processes. It could be useful in order to modulate brain networks that could be altered in some experimental models [48] that aim to emulate clinical alterations in human population. In addition, we have proved that the rTMS effects of 1 day of stimulation (100 Hz; 10 sessions; 30000 pulses) can endure up to 48 hours, leading to a brain metabolic activity enhancement in cortical regions distant to the stimulation focus, suggesting that rTMS effects have an impact into brain functional networks.…”

Section: Discussionmentioning

confidence: 99%

Equipment for Repetitive Transcranial Magnetic Stimulation

Pernia

Zorzo

Prieto³

et al. 2020

IEEE Trans. Biomed. Circuits Syst.

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Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique used for the treatment of a great variety of neurological disorders. The technique involves applying a magnetic field in certain areas of the cerebral cortex in order to modify neuronal excitability outside the skull. However, the exact brain mechanisms underlying rTMS effects are not completely elucidated. For that purpose, and in order to generate a pulsed magnetic field, a half-bridge converter controlled by a microcontroller has been designed to apply rTMS in small animals. Moreover, the small size of the rodent head makes it necessary to design a magnetic transducer, with the aim of focusing the magnetic field on selected brain areas using a specific and a small magnetic head. Then, our purpose was to compare the effects of five different rTMS dosages on the rat brain metabolic activity. The experimental results showed that one day of stimulation leads to an enhancement of brain metabolic activity in cortical areas, meanwhile with three days of stimulation it is possible to also modify subcortical zones, results that were not found when extending the number of rTMS applications up to seven days. In consequence, the number of pulses delivered might be an important parameter in rTMS protocols, highlighting its importance in rTMS impact.

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“…Some authors suggest that hippocampal dysfunction may be one of the leading factors in the development of depression, rather than the frequency of seizure or degree of disability [11–13, 41, 56]. In 2011, Gonçalves and Cendes demonstrated that patients with longer duration of epilepsy showed an increased risk of depression, however there was no association between seizure frequency and depression [32].…”

Section: Discussionmentioning

confidence: 99%

“…Also, clinical and experimental studies evidenced neurobiological mechanisms that could linkage epilepsy and depression symptoms, such as differences in neurotransmitters [12] and alterations in brain glucose metabolism and metabolic network in regions related to the pathophysiology of both epilepsy and depression [13]. Another factor that could contribute to depressive and anxiety symptoms in TLE is the hemisphere of epileptogenic focus, but this still remains uncertain, with studies pointing to prevalence of interictal depression in left-sided seizure foci [14,15], while others showing a tendency for greater depressive symptoms in presurgical right-sided seizure foci patients [14,15].The most frequent way to evaluate depressive and anxiety symptoms in epilepsy patients is by using scales and inventories that provide a quantitative measure of recurrent and severity of mood symptomatology experienced by the patients [16].…”

Section: Introductionmentioning

confidence: 99%

“…There is no consensus as to why this association exists, but the major agreement comes from the possibility that these comorbidities and TLE share similar neuroanatomic localizations [9–11]. Also, clinical and experimental studies evidenced neurobiological mechanisms that could linkage epilepsy and depression symptoms, such as differences in neurotransmitters [12] and alterations in brain glucose metabolism and metabolic network in regions related to the pathophysiology of both epilepsy and depression [13]. Another factor that could contribute to depressive and anxiety symptoms in TLE is the hemisphere of epileptogenic focus, but this still remains uncertain, with studies pointing to prevalence of interictal depression in left-sided seizure foci [14, 15], while others showing a tendency for greater depressive symptoms in presurgical right-sided seizure foci patients [14, 15].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Symptoms of depression can be more frequent in non-surgical patients with left lateralization of Temporal Lobe Epilepsy: A systematic review

Escobar¹,

Baroni²,

Radaell³

et al. 2020

Preprint

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Objective: Considering that the side of epileptogenic focus is a factor that could contribute to depressive and anxiety symptoms, we propose a systematic review searching for the prevalence of depression in TLE in non-surgical patients. Methods: We performed a literature search in PubMed/Medline, Web of Science and PsycNET for data from inception until January 2019. Results: After screening titles and abstracts, only 32 articles met the inclusion criteria. DSM/SCID is the main method utilized to psychiatric diagnosis. The majority of the studies did not perform neuropsychological evaluation. From 24 studies, most clinic cases of lateralization of epileptic focus depression symptoms showed lateralization in the left hemisphere. Nine studies were evaluated for individual depressive diagnosis, therefore, the analyzed data does not present statistical significance between right and left hemispheres. Significance: This study shows mood disorders are prevalent in epileptic patients undergoing clinical treatment. However, to date there is no correlation between lateralization of epilepsy and the prevalence of mood disorders or cognitive impairment. Well-conducted studies are needed to establish the correlation between the epilepsy lateralization and mood disorders.

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Depression comorbidity in epileptic rats is related to brain glucose hypometabolism and hypersynchronicity in the metabolic network architecture

Cited by 27 publications

References 42 publications

Imaging biomarkers of behavioral impairments: A pilot micro–positron emission tomographic study in a rat electrical post–status epilepticus model

Imaging biomarkers of behavioral impairments: A pilot micro–positron emission tomographic study in a rat electrical post–status epilepticus model

Equipment for Repetitive Transcranial Magnetic Stimulation

Symptoms of depression can be more frequent in non-surgical patients with left lateralization of Temporal Lobe Epilepsy: A systematic review

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