Africa’s contribution to the science of the Covid-19/Sars-CoV-2 pandemic
Bibliographic Data
| ID | 21879186 |
|---|---|
| Authors | Musa Abubakar Kana (0000-0002-5766-7610, Federal University Lafia, corresponding author), Ronald E Laporte (University of Pittsburgh), Ronald LaPorte (University of Pittsburgh), Assan Jaye (MRC Unit the Gambia) |
| Year | 2021 |
| Volume | 6 |
| Issue | 3 |
| Pages | e004059 |
| Publication date | 2021-03-01 |
| Open Access | Yes |
| Type | ARTICLE |
| Venue | BMJ Global Health (JOURNAL) |
| Journal identifiers | ISSN: 2059-7908 • E-ISSN: 2059-7908 |
| Publisher | BMJ (PUBLISHER • GB) |
| DOI | 10.1136/bmjgh-2020-004059 |
| PMID | 33648978 |
| OpenAlex | W3134555263 |
| Language | EN |
| Citations received | 3 |
| References cited | 13 |
Scn2a encodes voltage-gated sodium channel Na V 1.2, which mediates neuronal firing. The current paradigm suggests that Na V 1.2 gain-of-function variants enhance neuronal excitability resulting in epilepsy, whereas Na V 1.2 deficiency impairs neuronal excitability contributing to autism. In this paradigm, however, why about a third of patients with Na V 1.2 deficiency still develop seizures remains a mystery. Here we challenge the conventional wisdom, reporting that neuronal excitability is increased with severe Na V 1.2 deficiency. Using a unique gene-trap knockout mouse model of Scn2a , we found enhanced intrinsic excitabilities of principal neurons in the cortico-striatal circuit, known to be involved in Scn2a -related seizures. This increased excitability is autonomous, and is reversible by genetic restoration of Scn2a expression in adult mice. Mechanistic investigation reveals a compensatory downregulation of potassium channels including K V 1.1, which could be targeted to alleviate neuronal hyperexcitability. Our unexpected findings may explain Na V 1.2 deficiency-related epileptic seizures in humans and provide molecular targets for potential interventions. TEASER Severe Na V 1.2 deficiency results in neuronal hyperexcitability via the compensatory downregulation of potassium channels. HIGHLIGHTS Severe Na V 1.2 deficiency results in enhanced excitability of medium spiny neurons (MSNs) and pyramidal neurons in adult mice; Increased neuronal excitability in MSNs is accompanied by elevated voltage threshold; Na V 1.2 deficiency-related hyperexcitability is reversible with the restoration of Scn2a expression, and is autonomous; The expression of the K V 1.1 channel has a compensatory reduction in neurons with Na V 1.2 deficiency, and KV channels openers normalize the neuronal excitability; The enhanced excitability in brain slices translates to elevated in vivo firing commonly associated with seizures
Biology · Downregulation and upregulation · Epilepsy · Gene · Potassium channel · Sodium · Sodium channel · Chemistry · Long-Term Effects of COVID-19 · Misinformation and Its Impacts · Neuroscience · SARS-CoV-2 and COVID-19 Research · Biochemistry · Endocrinology
| Citations per year | 0.6 |
|---|---|
| Citation span | 2021 - 2023 (3) |
| Highly cited | No |