Table 1
Search Strategy
| Key Words and Combination | Number of Publications | ||
|---|---|---|---|
| Tremor AND Animal models | Total | Included | Excluded |
| Tremor AND mouse | 194 | 12 | 182 (not in English, 9; not relevant, 173) |
| Tremor AND rat | 413 | 37 | 376 (not in English, 15; not relevant, 361) |
| Tremor AND monkey | 470 | 15 | 455 (not in English, 31; not relevant, 424) |
| Total number of articles included for review | 94 | 4 | 90 (not in English, 9; not relevant, 81) |
| Total number of articles included from the references of the including articles | 68 | ||
| Final number of articles included for review | 5 | ||
| 73 | |||
Figure 1
Search Strategy. Flow diagram for the literature search results.
Figure 2
Characteristics of Harmaline-Induced Tremor in Mice. (A) A representative time-frequency plot of harmaline-induced mouse tremor, which shows that harmaline can induce action tremor at the peak frequency around 13–15 Hz. The tremor was induced by a single intraperitoneal injection of harmaline hydrochloride (Sigma) at 5 mg/kg into a WT C57BL/6J mouse, and the mouse tremor was measured using Convuls-1 sensing platform (Columbus Instruments), co-registered with a video-based motion detection (NeuroMotive, BlackRock microsystem) to separate action vs. rest tremor. (B) The quantification of movement intensity at different frequency, showing that tremor occurs at action but minimal at rest in harmaline-induced tremor mouse model.
Figure 3
Brain Circuitry for Tremor. Schematics for the brain circuitry involved in the tremor of animal models. The brain circuitry alterations in each animal model of tremor are highlighted. CF, Climbing Fiber; DCN, Deep Cerebellar Nucleus; IO, Inferior Olive; PC, Purkinje Cell; VL, Ventrolateral Nucleus of the Thalamus.
Table 2
Chemical- or Lesion-induced Animal Models of Tremor
| Chemical/Lesion | Tremor Type and Frequency (Hz) | Tremor Measurement | Reference | |
|---|---|---|---|---|
| Mouse | Harmaline-induced | 10–16 Hz body tremor | Force plate-based measurement | 19 |
| 6-OHDA-induced | 4–5 Hz body tremor | Electromyography or force plate-based measurement | 44 | |
| Galantamine-induced | Oral tremor (3–7.5 Hz frequency range, with a peak frequency of approximately 6 Hz) | Observation | 69 | |
| Oxotremorine-induced and arecoline-induced | Tremor | Multiple electrical physiological signals real-time analyzer | 70 | |
| Phenol-induced | Tremor | Observation | 71 | |
| Pilocarpine-induced | Oral tremor | Observation | 72 | |
| Rat | Harmaline-induced | 8–12 Hz body tremor | Force plate-based measurement | 19 |
| Chlordecone-induced | Tremor | Force plate setting | 73 | |
| Ethanol withdrawal physostigmine-induced, arecoline-induced | Tremor(6–7 Hz)tremor (11–13 Hz) tremor (peak of 13 Hz) | Objective measure, not detailed in method | 74 | |
| Nicotine-induced | Tremor | Observation | 75 | |
| p-Chloroamphetamine-induced | Tremor | Observation | 76 | |
| p,p'-DDT-induced | Tremor | Observation | 77 | |
| Tacrine-induced | Oral tremor | Observation | 78 | |
| Monkey | MPTP-induced | 5–7 Hz limb tremor | Accelerometer | 43 |
| Electrical coagulation of the brainstem area including the substantia nigra and the red nucleus | Resting tremor (stable frequency of 4.46 ± 0.59 Hz) | An accelerometer connected to a computer system | 79 | |
| Repeated electrode penetration of the dentate and interpositus nuclei | Change the physiological tremor frequency from 11–13 Hz to 5–7 Hz | EMG | 80 | |
| Partial cerebellectomy (including unilateral DCN) | Tremor | EMG | 81 |
Table 3
Genetic Animal Models of Tremor
| Gene/Lesion | Tremor Type (Hz) | Tremor Measure | Ataxia/Others | Cerebellar Pathology/Physiology | Reference | |
|---|---|---|---|---|---|---|
| Mouse | Car8 mutation | Tremor (4–14 Hz) | Tremor monitor (San Diego instruments) | Ataxia | Microzonal organization defects, abnormal Purkinje cell firing | 53 |
| crv4 mutation | Intention tremor | Observation | Ataxia | 83 | ||
| Cp/Heph mutation | Tremor | Observation | Ataxia | 84 | ||
| D801N mutation | Tremor | Observation | Abnormal motor coordination | 85 | ||
| GABAA α1 subunit knockout | Tremor (15–19 Hz) | Tremor measured by suspending the tail and attached to the stereo speaker | Absent spontaneous GABAergic inhibitory postsynaptic potentials | 66 | ||
| NPC1 mutation | Tremor | Observation | Motor impairment, hyperactivity, impaired learning and memory | 86 | ||
| SCN8A mutation | Tremor | Observation | Ataxia and dystonia | Impaired repetitive firing of Purkinje cells in cerebellar slices | 87 | |
| SOD1 mutation | Tremor | Observation | Loss of extension reflex in hind-limbs, decreased grip strength and paralysis | 88 | ||
| SULT4A1 mutation | Tremor | Observation | Ataxia and absence seizures | 89 | ||
| Vglut2 deletion in the climbing fiber synapses | Tremor (4–14 Hz) | Tremor monitor (San Diego instruments) | Dystonia | Abnormal Purkinje cell simple spike firing (Silencing climbing fiber synaptic transmission) | 90 | |
| Wdr81 mutation | Tremor | Observation | Abnormal gait | Purkinje cell degeneration | 91 | |
| β-III spectrin knockout | Tremor | Observation | Motor incoordination and a wide hindlimb gait | Purkinje cell loss and cerebellar atrophy | 92 | |
| Fig4 knockout | Intention tremor | Observation | hypomyelination of the cerebellum and spongiform degeneration in the deep cerebellar nuclei | 93 | ||
| Pura knockout | Action tremor | Observation | Waddling gait | Reduced number of Purkinje cells and granule cells | 94 | |
| Sticky mouse (Aars mutation) | Tremor | Observation | Ataxia | Purkinje cell degeneration | 95 | |
| Scrambler mouse | Body tremor | Observation | Abnormal gait | 96 | ||
| Toppler mouse | Action tremor | Observation | Ataxia | Purkinje cell loss | 97 | |
| Wobbler mouse | Head tremor | Observation | Unsteady gait and muscle atrophy | 98 | ||
| Weaver mouse | Tremor | Observation | Ataxia and hypertonia | 99 | ||
| Rat | VF mutation | Generalized tremor (especially the caudal body) that peaks between 4–8 weeks and gradually subsides | Observation | Abnormal myelin-associated vacuoles in the white matter of cerebellum | 100 | |
| Shaker mutation | Tremor (4–5 Hz) | Force plate-based measurement | Ataxia | Purkinje cell degeneration | 60 | |
| TRM/Kyo mutation | Whole body tremor, responsive to propranolol | Observation | 102 | |||
| Hamster | bt mutation | Tremor | Observation | Defective myelination in the central nervous system | 101 |