Table 1.
Recent evidence of therapeutic approaches to non-motor symptoms of PD in animal models.
| Treatment | Animal Model | Neuropsychiatric Symptoms | Sleep Disorders | Autonomic Symptoms |
Sensory
Symptoms |
|---|---|---|---|---|---|
| Pharmacological Treatments | |||||
| DAergic Treatments | |||||
| L-DOPA | 6-OHDA-lesioned rats [143] | - | - | - | ↑Pain threshold |
| L-DOPA | MPTP-lesioned monkeys [31] | - | ↑Sleep quality | - | - |
| SKF38393 | MPTP-lesioned monkeys [98] | - | ↑EDS & REM | - | - |
| L-DOPA | 6-OHDA-lesioned mice [148] | No effect on anxiety & depression |
- | - | - |
| - | 6-OHDA-lesioned rats [149] | ↑Anxiety | - | - | - |
| MAO-B Inhibitors | |||||
| Selegiline | CD157/BST1 KO mice [29] | ↓Anxiety & ↓Depression | - | - | - |
| Imidazole | MPTP-lesioned mice [84] | ↓Anxiety & ↓Depression | - | - | ↑Pain threshold |
| Immunotherapy | |||||
| Anti-α-Syn | α-Syn TG mice [150-152] | ↑Cognition | - | - | - |
| A2AR Antagonists/Genetic Ablation | |||||
| Istradefylline | MPTP-lesioned monkeys [28] | ↑Cognition | - | - | - |
| KW6002 | MPTP-lesioned monkeys [67] | ↑Cognition | - | - | - |
| A2AR KO | Intra-hippocampal α-Syn fibril-infused mice [60] | ↑Cognition | - | - | - |
| A2AR KO | 6-OHDA-lesioned rats [153] | ↑Cognition | - | - | - |
| mGluR5 Antagonists | |||||
| MPEP | α-Syn TG mice [42] | ↑Cognition | - | - | - |
| MPEP | MPTP-lesioned rats [62] | ↑Cognition | - | - | - |
| Anti-Oxidative and Anti-Inflammatory Treatments | |||||
| CuII(atsm) | α-Syn TG mice [58] | ↑Cognition | - | - | - |
| Resveratrol | α-Syn TG mice [59] | ↑Cognition | - | - | - |
| Apocynin | LRRK2 TG mice [136] | ↓Anxiety & ↓Depression | - | - | - |
| Melatonin | LRRK2 TG mice [99] | - | ↑Sleep quality | - | - |
| PLX3397 | 6-OHDA-lesioned rats [77] | ↓Depression | - | - | - |
| Curcumin | Rotenone-lesioned rats [32, 85] | ↓Depression | - | - | - |
| Quercetin | Rotenone-lesioned rats [86] | ↑Cognition & ↓Depression | - | - | - |
| Baicalein | Rotenone-lesioned mice [87] | ↓Depression | - | - | - |
| TLR4 KO | 6-OHDA-lesioned mice [82] | ↑Cognition & ↓Depression | - | - | - |
| Rapamycin | 6-OHDA-lesioned mice [44] | ↑Cognition, ↓Anxiety & ↓Depression | - | - | - |
| TLR4 KO | MPTP-lesioned mice [83] | ↓Anxiety & ↓Depression | - | - | - |
| Thioredoxin-1 | MPTP-lesioned mice [154] | ↑Cognition | - | - | - |
| Other Pharmacological Treatments | |||||
| Neuropeptide-S | 6-OHDA-lesioned rats [75] | ↑Cognition, ↓Anxiety & ↓Depression | - | - | - |
| Apamin | 6-OHDA-lesioned rats [76] | ↑Cognition, ↓Anxiety & ↓Depression | - | - | - |
| Exendin-4 | 6-OHDA-lesioned rats [81] | ↑Cognition & ↓Depression | - | - | - |
| Other Pharmacological Treatments | |||||
| Atorvastatin | MPTP-lesioned rats [63] | ↑Cognition & ↓Depression | - | - | - |
| Nobiletin | MPTP-lesioned mice [64] | ↑Cognition | - | - | - |
| Ethyl pyruvate | MPTP-lesioned mice [65] | ↑Cognition | - | - | - |
| NTRC 3531-0 | Rotenone-lesioned mice [155] | ↑Cognition | - | ↑Intestinal transit | - |
| Oligonucleotide | α-Syn TG mice [73] | ↓Depression | - | - | - |
| GDNF | MitoPark mice [74] | ↓Depression | - | - | - |
| Pramipexole | 6-OHDA-lesioned rats [156] | ↓Depression | - | - | - |
| Reboxetine | 6-OHDA-lesioned mice [148] | ↓Anxiety & ↓Depression | - | - | - |
| Desipramine | 6-OHDA-lesioned mice [148] | No effect on anxiety & depression |
- | - | - |
| Clioquinol | MPTP-lesioned monkeys [157] | - | - | ↓Constipation | - |
| Citalopram | 6-OHDA-lesioned rats [142] | - | - | - | ↑Pain threshold |
| Mulberry fruit | MPTP-lesioned mice [52] | - | - | - | ↑Olfaction |
| Non-Pharmacological Treatments | |||||
| Exercise | AAV-α-Syn overexpressing rats [35] | ↑Cognition | - | - | - |
| 6-OHDA-lesioned rats [61] | ↑Cognition & ↓Depression | - | - | - | |
| MPTP-lesioned mice [66] | ↑Cognition | - | - | - | |
| MPTP-lesioned mice [158] | No effect on cognition | - | - | - | |
| Environmental enrichment |
α-Syn TG mice [34] | ↓Anxiety | - | - | - |
| STN-DBS/ Duloxetine |
6-OHDA-lesioned rats [144, 145, 159, 160] | - | - | - | ↑Pain threshold |
| Stem cell therapy | 6-OHDA-lesioned rats [113, 161] | - | - | ↑Voiding function | - |
Abbreviations: 6-OHDA, 6-hydroxydopamine; AAV, adeno-associated virus; A2AR, adenosine A2A receptor; α-Syn, α-synuclein; CuII(atsm), diacetylbis(N(4)-methylthiosemicarbazonato) copper(II); DA, dopamine; EDS, excessive daytime sleepiness; GDNF, glial-derived neurotrophic factor; KO, knockout; KW6002, A2AR antagonists; L-DOPA, l-3,4-dihydroxy-L-phenylalanine; LRRK2, leucine-rich repeat kinase 2; MAO-B, monoamine oxidase B; mGluR5, metabotropic glutamate receptor 5; MPEP, 2-methyl-6-(phenylethynyl)pyridine; MPTP, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; NMDAR, N-methyl D-aspartate receptor; NTRC 3531-0, tryptophan 2,3-dioxygenase inhibitor; PLX3397, pexidartinib; REM, rapid eye movement; SKF38393, DAergic D1-like receptor agonist; STN-DBS, Subthalamic deep brain stimulation; TG, transgenic; TLR, Toll-like receptor.