Parvalbumin Role in Epilepsy and Psychiatric Comorbidities: From Mechanism to Intervention

Author(s)

Godoy, Livea Dornela ; Prizon, Tamiris ; Rossignoli, Matheus Teixeira ; Leite, Joao Pereira ; Liberato, Jose Luiz

• Document type: Journal article
• Source: FRONTIERS IN INTEGRATIVE NEUROSCIENCE; v. 16, p. 28-pg., 2022-02-17.

Abstract

Parvalbumin is a calcium-binding protein present in inhibitory interneurons that play an essential role in regulating many physiological processes, such as intracellular signaling and synaptic transmission. Changes in parvalbumin expression are deeply related to epilepsy, which is considered one of the most disabling neuropathologies. Epilepsy is a complex multi-factor group of disorders characterized by periods of hypersynchronous activity and hyperexcitability within brain networks. In this scenario, inhibitory neurotransmission dysfunction in modulating excitatory transmission related to the loss of subsets of parvalbumin-expressing inhibitory interneuron may have a prominent role in disrupted excitability. Some studies also reported that parvalbumin-positive interneurons altered function might contribute to psychiatric comorbidities associated with epilepsy, such as depression, anxiety, and psychosis. Understanding the epileptogenic process and comorbidities associated with epilepsy have significantly advanced through preclinical and clinical investigation. In this review, evidence from parvalbumin altered function in epilepsy and associated psychiatric comorbidities were explored with a translational perspective. Some advances in potential therapeutic interventions are highlighted, from current antiepileptic and neuroprotective drugs to cutting edge modulation of parvalbumin subpopulations using optogenetics, designer receptors exclusively activated by designer drugs (DREADD) techniques, transcranial magnetic stimulation, genome engineering, and cell grafting. Creating new perspectives on mechanisms and therapeutic strategies is valuable for understanding the pathophysiology of epilepsy and its psychiatric comorbidities and improving efficiency in clinical intervention. (AU)

• FAPESP's process: 16/17882-4 - Drug-resistant epilepsies: diagnostic challenges, associated comorbidities and new experimental approaches
• Grantee: João Pereira Leite
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/01510-6 - Study of the neural processing of meso-cortico-limbic circuitry during anhedonic-type behavior and its modulation by the endocannabinoid system
• Grantee: Matheus Teixeira Rossignoli
• Support Opportunities: Scholarships in Brazil - Post-Doctoral