Developmental Changes in Dendritic Spine Morphology in the Striatum and Their Alteration in an A53T α-Synuclein Transgenic Mouse Model of Parkinson’s Disease

Abstract

Developmental changes in dendritic spine morphology in the striatum and their alteration in an A53T α-synuclein transgenic

Geometry and the Organizational Principle of Spine Synapses along a Dendrite

“…Pre-embedding immunogold labeling was conducted as described in Parajuli et al (2020b ). We perfused a mouse with 75 ml of fixative containing 4% PFA and 0.05% glutaraldehyde.…”

Quantification of Dendritic Spines Remodeling under Physiological Stimuli and in Pathological Conditions

“…To highlight the role of dendritic spines in various context-dependent conditions, we have summarized dendritic spine remodeling in physiological processes and upon stimulation ( Table 1 ) induced by postsynaptic receptor antagonism [ 15 ], postsynaptic receptor agonism [ 16 , 17 ], genetic modifications [ 18 , 19 , 20 ], Chemically induced LTP [ 21 , 22 , 23 , 24 , 25 ], LTD (long-term depression) [ 26 ], sensory experience [ 27 , 28 ], spatial memory and learning [ 29 ], physical environmental stimuli [ 30 , 31 , 32 ]. Pathological processes ( Table 2 ) were categorized into brain diseases underling neurodegenerative (Alzheimer’s disease [ 33 , 34 , 35 ], Parkinson disease [ 36 ], Fragile X Syndrome [ 37 , 38 ], Down Syndrome [ 39 ], Rett Syndrome [ 40 , 41 ], Autism Spectrum Disorder [ 42 ], Huntingtin Disease [ 43 ]), neuropsychiatric (Schizophrenia [ 44 ], Depression [ 45 , 46 , 47 ]), Stroke [ 48 ], Epilepsy [ 49 ], and infectious diseases such as Prion Disease [ 50 ], HIV infection [ 51 ], Influenza Infection [ 52 ], Toxoplasmosis [ 53 ] and Antiviral Responses [ 54 ].…”

“…Thus, the imaging speed is the main factor limiting the application of stochastic microscopy techniques in live imaging and in high throughput analysis. Thus, the studies related to physiological and pathological processes of spine remodeling are mainly addressed to fluorescent confocal microscopy [ 16 , 18 , 19 , 21 , 22 , 29 , 42 , 43 , 44 , 46 , 47 , 50 ] due to the possibility to analyze the higher number of spines than in EM [ 23 , 33 , 36 ], and STED [ 27 , 37 , 38 , 39 , 40 , 41 , 45 , 48 ]. The mechanisms underlying spine structure are mainly performed using EM and STED due to the high-resolution imaging.…”

“…Recently, methods for unsupervised classification or non-classification approaches have been developed, see [ 163 ] for a review. Thus, to assess the morphometric changes, either a classification scheme can be followed, where the percentages in spines categories are compared [ 19 , 29 , 33 , 42 , 43 , 44 , 46 ], or alternatively, a direct comparison of certain morphological parameters is performed [ 16 , 18 , 19 , 21 , 23 , 29 , 34 , 36 , 37 , 42 , 47 , 48 , 49 ]. Quite often, a dimensionless ratio of certain parameters is analyzed, the advantage of such an approach is that it measures only the changes in spine geometrical shape independently of changes in size [ 16 , 18 , 19 , 21 , 29 , 47 ].…”

Advances of Mechanisms-Related Metabolomics in Parkinson’s Disease

“…The initial link between the SNCA gene and PD was found by Polymeropoulos et al (1997) when a missense mutation (A53T) of SNCA was implicated in patients with autosomal dominant Parkinsonism from a large Italian family. Shortly thereafter, accumulating evidence has shown the mutations of A30Pro ( Kruger et al, 1998 ), E46K ( Zarranz et al, 2004 ), H50Q, G51D, and A53E in the alpha-synuclein gene ( Parajuli et al, 2020 ). All six-point mutants have been involved in a-Syn overexpression, accumulation, and aggregation, conferring the risk of the disease’s onset or causing familial PD ( Singleton et al, 2013 ).…”