| First Author | Hascup KN | Year | 2021 |
| Journal | J Neurochem | Volume | 156 |
| Issue | 4 | Pages | 513-523 |
| PubMed ID | 33107040 | Mgi Jnum | J:302533 |
| Mgi Id | MGI:6507818 | Doi | 10.1111/jnc.15224 |
| Citation | Hascup KN, et al. (2021) Riluzole attenuates glutamatergic tone and cognitive decline in AbetaPP/PS1 mice. J Neurochem 156(4):513-523 |
| abstractText | We have previously demonstrated hippocampal hyperglutamatergic signaling occurs prior to plaque accumulation in AbetaPP/PS1 mice. Here, we evaluate 2-Amino-6-(trifluoromethoxy) benzothiazole (riluzole) as an early intervention strategy for Alzheimer's disease (AD), aimed at restoring glutamate neurotransmission prior to substantial Beta amyloid (Abeta) plaque accumulation and cognitive decline. Male AbetaPP/PS1 mice, a model of progressive cerebral amyloidosis, were treated with riluzole from 2-6 months of age. Morris water maze, in vivo electrochemistry, and immunofluorescence were performed to assess cognition, glutamatergic neurotransmission, and pathology, respectively, at 12 months. Four months of prodromal riluzole treatment in AbetaPP/PS1 mice resulted in long-lasting procognitive effects and attenuated glutamatergic tone that was observed six months after discontinuing riluzole treatment. Riluzole-treated AbetaPP/PS1 mice had significant improvement in long-term memory compared to vehicle-treated AbetaPP/PS1 mice that was similar to normal aging C57BL/6J control mice. Furthermore, basal glutamate concentration and evoked-glutamate release levels, which were elevated in vehicle-treated AbetaPP/PS1 mice, were restored to levels observed in age-matched C57BL/6J mice in AbetaPP/PS1 mice receiving prodromal riluzole treatment. Abeta plaque accumulation was not altered with riluzole treatment. This study supports that interventions targeting the glutamatergic system during the early stages of AD progression have long-term effects on disease outcome, and importantly may prevent cognitive decline. Our observations provide preclinical support for targeting glutamate neurotransmission in patients at risk for developing AD. Read the Editorial Highlight for this article on page 399. |
