The 5-HT1F Receptor Agonist Lasmiditan improves Cognition and Ameliorates Associated Cortico-Hippocampal Pathology in Aging Parkinsonian Mice
Ishii, A.; Meredith, J. R.; Corenblum, M. J.; Bernard, K.; Wene, P.; Menakuru, N.; Santiago, P. V.; Schnellmann, R. G.; Madhavan, L.
Show abstract
While the etiopathology of Parkinsons disease (PD) is complex, mitochondrial dysfunction is established to have a central role. Thus, mitochondria have emerged as targets of therapeutic interventions aiming to slow or modify PD progression. We have previously identified serotonergic 5-HT1F receptors as novel mediators of mitochondrial biogenesis (MB) - the process of producing new mitochondria. Given this, here, we assessed the therapeutic potential of the FDA-approved 5-HT1F receptor agonist, lasmiditan, in a chronic progressive PD model (Thy1-aSyn line 61 mice). It was observed that systemic lasmiditan exhibited robust brain penetration and reversed cognitive deficits in young (4-5.5 months old) Thy1-aSyn mice (1mg/kg, every other day). Anxiety-like behavior was also improved while motor function remained unaffected. These behavioral changes were associated with enhanced MB and mitochondrial function, paired with reduced alpha-synuclein aggregation particularly in cortico-hippocampal regions. Furthermore, in older (10-11.5 months old) mice, although the effects were milder, daily lasmiditan administration increased MB and bettered cognitive abilities. In essence, these findings indicate that repurposing lasmiditan could be a potent strategy to address PD-related cognitive decline.
Matching journals
The top 14 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Developmental exposure to the organochlorine pesticide dieldrin causes male-specific exacerbation of α-synuclein-preformed fibril-induced toxicity and motor deficits 96%
- LRRK2 kinase inhibition protects against Parkinson's disease-associated environmental toxicants 95%
- The industrial solvent trichloroethylene induces LRRK2 kinase activity and dopaminergic neurodegeneration in a rat model of Parkinson's disease 95%
Similar papers in this journal
- Medial prefrontal cortex Notch1 signalling mediates methamphetamine-induced psychosis via Hes1-dependent suppression of GABAB1 receptor expression. 94%
- Early activation of cellular stress and death pathways caused by cytoplasmic TDP-43 in the rNLS8 mouse model of ALS/FTD 94%
- Oxytocin administration in neonates shapes the hippocampal circuitry and restores social behavior in a mouse model of autism. 93%
Similar papers in this journal
- Sex-dimorphic neuroprotective effect of CD163 in an α-synuclein mouse model of Parkinson's disease 95%
- Protection from α-synuclein-induced dopaminergic neurodegeneration by overexpression of the mitochondrial import receptor TOM20 in the rat midbrain 95%
- Early synaptic changes and reduced brain connectivity in PD-like mice with depressive phenotype 95%
Similar papers in this journal
Similar papers in this journal
- Elevated Ubiquitin Phosphorylation by PINK1 Contributes to Proteasomal Impairment and Promotes Neurodegeneration 94%
- Cell autonomous role of leucine-rich repeat kinase in protection of dopaminergic neuron survival 94%
- A peptide-neurotensin conjugate that crosses the blood-brain barrier induces pharmacological hypothermia associated with anticonvulsant, neuroprotective and anti-inflammatory properties following status epilepticus in mice 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.