Previous studies demonstrate that intrastriatal injections of fibrillar alpha-synuclein (a- @entity15735 ) into @entity19 induce @entity191 ( @entity191 )-like Lewy body (LB) pathology formed by aggregated a- @entity15735 in anatomically interconnected regions and significant @entity528 . The aim of the current study was to evaluate whether exogenous @entity19 a- @entity15735 pre-formed fibrils (PFF) injected into the striatum of @entity35 would result in accumulation of LB-like intracellular inclusions and @entity528 . @entity35 received unilateral intrastriatal injections of either non-fibrillized recombinant a- @entity15735 or PFF @entity19 a- @entity15735 in 1- or 2- sites and were euthanized at 30, 60 or 180 days post-injection (pi). Both non-fibrillized recombinant a- @entity15735 and PFF a- @entity15735 injections resulted in phosphorylated a- @entity15735 intraneuronal accumulations (i.e., diffuse Lewy neurite (LN)- and LB-like inclusions) with significantly greater accumulations following PFF injection. LB-like inclusions were observed in several areas that innervate the striatum, most prominently the frontal and insular cortices, the amygdala, and the substantia nigra pars compacta (SNpc). a- @entity15735 accumulations co-localized with ubiquitin, @entity10407 , and were @entity7732 -positive and proteinase-k resistant, suggesting that PFF-induced pathology exhibits properties similar to @entity1 LBs. Although a- @entity15735 inclusions within the SNpc remained ipsilateral to striatal injection, we observed bilateral reductions in nigral @entity935 neurons at the 180-day time-point in both the 1- and 2-site PFF injection paradigms. PFF injected @entity35 exhibited bilateral reductions in striatal dopaminergic innervation at 60 and 180 days and bilateral decreases in @entity4926 ; however, @entity935 reduction was observed only in the striatum ipsilateral to PFF injection. Although the level of @entity935 asymmetry in PFF injected @entity35 at 180 days was insufficient to elicit motor deficits in @entity4944 -induced rotations or forelimb use in the cylinder task, significant disruption of ultrasonic vocalizations was observed. Taken together, our findings demonstrate that a- @entity15735 PFF are sufficient to seed the pathological conversion and propagation of endogenous a- @entity15735 to induce a progressive, neurodegenerative model of a-synucleinopathy in @entity35 .

Intrastriatal injection of pre-formed XXXX a-synuclein fibrils into @entity35 triggers a-synuclein pathology and bilateral @entity528 .

@entity1 :: ('9606', 'Species') :: ['human'] @entity15735 :: ('23336', 'Gene') :: ['syn', 'Syn'] @entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity935 :: ('MESH:D004298', 'Chemical') :: ['dopamine'] @entity10407 :: ('23636', 'Gene') :: ['p62'] @entity191 :: ('MESH:D010300', 'Disease') :: ["Parkinson's disease", 'PD'] @entity35 :: ('10116', 'Species') :: ['Sprague-Dawley rats', 'rats'] @entity7732 :: ('MESH:C009462', 'Chemical') :: ['thioflavin-S'] @entity4926 :: ('MESH:D006719', 'Chemical') :: ['homovanillic acid'] @entity528 :: ('MESH:D009410', 'Disease') :: ['nigrostriatal degeneration'] @entity4944 :: ('MESH:D000661', 'Chemical') :: ['amphetamine']
@entity19 :: (10090,Species) :: ['mouse']
