Construct, Face, and Predictive Validity of Parkinson’s Disease Rodent Models
Abstract
:1. Introduction
2. Construct Validity
2.1. Degeneration of Dopaminergic Neurons
2.2. Lewy Bodies
2.3. Gene Mutations
2.3.1. SNCA
2.3.2. PARKIN
2.3.3. PINK1
2.3.4. DJ-1
2.3.5. Genetic Variability and Clinical Trial
3. Face Validity
3.1. Motor Symptoms
3.1.1. Akinesia, Bradykinesia, and Hypokinesia
3.1.2. Muscle Rigidity
3.1.3. Resting Tremors
3.1.4. Gait Abnormalities
3.2. Non-Motor Symptoms
3.2.1. Sleep Abnormalities
3.2.2. Gastrointestinal Dysfunction
3.2.3. Anxiety and Depression
4. Predictive Validity
4.1. Pharmacological Treatments
4.2. Treatment Adverse Effect
4.3. Surgical Treatments
5. Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Model | Da Neurons Loss | Asyn-Aggregation |
---|---|---|
6-OHDA | Yes [7,12,13,14] | No [15] |
MPTP | Yes [16] | No |
RESERPINE | Yes [17,18] | Yes [19] |
ROTENONE | Yes [20,21,22] | Yes [20,21,22] |
PARAQUAT | Yes [23,24,25] | Yes [26,27] |
PFFs | Yes [28,29,30] | Yes [28,29,30] |
AAV-aSYN | Yes [31,32] | Yes [31,32] |
TRANSGENIC | Yes [33] | Yes [33,34,35,36] |
Model | Motor Symptoms | Tests for Motor Symptoms | Non-Motor Symptoms | Tests for Non-Motor Symptoms |
---|---|---|---|---|
6-OHDA | Dysfunctions in locomotor activities (akinesia, bradykinesia, hypokinesia), muscle rigidity [123,124], dyskinesia, and gait abnormalities [90]. | Open field, rotarod, pole test [125], tail suspension test (TST), tail suspension swing test (TSST) [126], Catwalk [127,128], rotational sensitization [129], grasping test or movement-induced reflex electromyographic activity [123,124], AIMs and other rating scales for dyskinesia [130,131], rotational motor behavior (apomorphine or amphetamine tests) [132], and cylinder test [133]. | Sleep abnormalities [134] Gastrointestinal dysfunction [135] Anxiety and depression [136] | EEG Gastric emptying [135] Sucrose preference test Forced swimming test Open field test [136] |
MPTP | Dysfunctions in locomotor activities (akinesia, bradykinesia, hypokinesia), dyskinesia, resting tremors, muscle rigidity, and gait abnormalities [137,138,139]. | Open field, rotarod, balance beam test [140] stepping test [141], pole test [142], horizontal and vertical grid tests [143], swim-test [144], catalepsy test, cylinder test, Catwalk [128]. | Sleep abnormalities [145] Gastrointestinal dysfunction [146] Anxiety and depression [136] | EEG [145] Stool Collection [146] Sucrose preference test Forced swimming test Open field test [136] |
RESERPINE | Akinesia [147], oral dyskinesia [148,149], and muscle rigidity. | Open field, rotarod, catalepsy test, and oral dyskinesia assessment [148,150,151]. | Sleep abnormalities [152] Anxiety [153] depression [154] | EEG [152] Open field Elevated plus maze [154], |
ROTENONE | Dysfunctions in locomotor activities (akinesia, bradykinesia, hypokinesia), muscle rigidity [155], gait abnormalities [156]. | Open field, rotarod, pole test, forced swimming test [157], catalepsy test, cylinder test. | Gastrointestinal dysfunction [158] Anxiety and depression [136] | Stool collection [159] Urine collection [159] Gastric emptying [158] Bead latency [160] Sucrose preference test Forced swimming test Open field test [136] |
PARAQUAT | Dysfunctions in locomotor activities (akinesia, bradykinesia, hypokinesia) [161], and forelimb rigidity [162]. | Open field, rotarod, inclined plane test, swimming test, catalepsy test, wire suspension test [161]. | Gastrointestinal dysfunction [163] Anxiety and depression [164] | Gastric motility [163] Sucrose preference test Forced swimming test Open field test Elevated plus maze [164] |
PFFs | Dysfunctions in locomotor activities (akinesia, bradykinesia, hypokinesia) [28,147], dyskinesia. | Open field, rotarod, wire hang test, tail suspension test (TST) [28], muscular strength test, elevated plus maze test, forced swim test, Y-maze test, apomorphine-induced rotational behavior test [165]. | Sleep abnormalities [166] Gastrointestinal dysfunction [167] Anxiety and depression [168] | EEG [166] Stool collection [167] Open field Elevated plus maze Tail suspension [168] |
GENETIC | Dysfunctions in locomotor and sensorimotor activities (akinesia, bradykinesia, hypokinesia) [169], dyskinesia [170], and gait abnormalities [171]. | Open field, rotarod, tapered balance beam test [171], pole test, adhesive removal test [172], grip strength [173], tail suspension test [174], AIM scores [170], cylinder test [175], ink test [98]. | Sleep Abnormalities [176] Gastrointestinal dysfunction [177] | EEG [176] Stool collection [177] |
Treatment | Humans | Rodents |
---|---|---|
Pharmacological Treatment | ||
Levodopa | 300–1500 mg/day [203,204] | 12.5–100 mg/kg [205,206] |
Pramipexole | 0.125–4.5 mg/day [203,204] | 0.05–1 mg/kg [207,208] |
Rasagiline | 1 mg/day [203] | 1 mg/kg [209] |
Dyskinesia | ||
Levodopa | - | 1–300 mg/kg [210] |
Dyskinesia Treatment | ||
Amantadine | 300 mg/day [211] | 10–60 mg/kg [212] |
Entacapone | 600–1600 mg/day [203] | 30 mg/kg/day [213] |
Clozapine | 39.4 + −4.5 mg/day [214] | 8 mg/kg dose [215] |
Surgical TreatmENT | ||
DBS | 130–185 Hz; 60–90 μs pulses [216], eletrodes size: 6 mm2 [217] | 130–185 Hz; 60–90 μs pulses [218], eletrodes size: 1–100 μm2 [217]. |
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Guimarães, R.P.; Resende, M.C.S.d.; Tavares, M.M.; Belardinelli de Azevedo, C.; Ruiz, M.C.M.; Mortari, M.R. Construct, Face, and Predictive Validity of Parkinson’s Disease Rodent Models. Int. J. Mol. Sci. 2024, 25, 8971. https://doi.org/10.3390/ijms25168971
Guimarães RP, Resende MCSd, Tavares MM, Belardinelli de Azevedo C, Ruiz MCM, Mortari MR. Construct, Face, and Predictive Validity of Parkinson’s Disease Rodent Models. International Journal of Molecular Sciences. 2024; 25(16):8971. https://doi.org/10.3390/ijms25168971
Chicago/Turabian StyleGuimarães, Rayanne Poletti, Maria Clara Souza de Resende, Miguel Mesquita Tavares, Caio Belardinelli de Azevedo, Miguel Cesar Merino Ruiz, and Márcia Renata Mortari. 2024. "Construct, Face, and Predictive Validity of Parkinson’s Disease Rodent Models" International Journal of Molecular Sciences 25, no. 16: 8971. https://doi.org/10.3390/ijms25168971