With a view to test the significance of TRPV3 in cerebellar function, TRPV3-agonist (eugenol) or -inhibitors [ruthenium red or isopentenyl pyrophosphate (IPP)] were administered stereotaxically intra-cerebellum and motor responses analyzed.
Treatment with the COX-2 inhibitor NS398 during 5 days prevented the deficits in cerebellar function and the cerebellar microglia reactivity in MAGL KO, without affecting hippocampal reactivity.
Our observation not only emphasizes the central role of mGluR1-mediated signaling in cerebellar function and neurodevelopment but also provides valuable insights into the early clinical signs of recessive ataxia due to GRM1 pathogenic variants that were not reported previously.
Treatment with the COX-2 inhibitor NS398 during 5 days prevented the deficits in cerebellar function and the cerebellar microglia reactivity in MAGL KO, without affecting hippocampal reactivity.
Our results define a role for Sox2 in cerebellar function and development, and identify a functional requirement for Sox2 within postnatal BG, of potential relevance for ataxia in mouse mutants, and in human patients.
This reduced motor performance of Ano2 <sup>-/-</sup> mice highlights the significance of inhibitory control for cerebellar function and introduces calcium-dependent short-term ionic plasticity as an efficient control mechanism for neural inhibition.
As a positive control, the same cerebellar tests were conducted in 13 patients with familial hemiplegic migraine type 1 (FHM1; age range 19-64; 69% female) all carrying a CACNA1A mutation known to affect cerebellar function.
The performance of the SCA7(266Q/5Q) knock-in mice was significantly improved on two behavioural tests sensitive to cerebellar function: the Locotronic® Test of locomotor function and the Beam Walking Test of balance, motor coordination and fine movements, which are affected in patients with spinocerebellar ataxia 7.
We propose that a cystatin B multiprotein complex has a specific cerebellar function and that the loss of this function might contribute to the disease in EPM1 patients.