Table 5.
Effect of rapamycin on the central nervous system of mice
| Model | Rapa dose | Effect of rapa treatment | Reference |
|---|---|---|---|
| Alzheimer’s disease | |||
| 3xTg-AD | 14 ppm | Cognition improved; Aβ and tau pathology ameliorated. | [62] |
| hAPP (J20) | 14 ppm | Cognition improved and Aβ aggregates reduced. | [63] |
| 3xTg-AD | 14 ppm | Life-long rapa reduced Aβ and tau pathology, and improved cognition. | [65] |
| hAPP (J20) | 14 ppm | Restored CBF and vascular density, reduced Aβ, and improved cognition. | [127] |
| P301S | 15 mg/kg i.p. | Reduced cortical tau tangles, forebrain insoluble, tau and astrogliosis. | [66] |
| APP/PS1 | 20 mg/kg, i.p.* | Enhanced Aβ clearance by autophagy and improved cognition | [128] |
| Tau P301L | 15 mg/kg i.p. | Reduced tau-induced neuronal loss, synaptotoxicity, and astrogliosis. | [67] |
| APOE4 | 14 ppm | Improved CBF and blood brain barrier integrity and learning deficits. | [69] |
| hAPP (J20)* | 14 ppm | Prevented blood brain barrier breakdown. | [158] |
| Ts65Dn | 1 μ/animal internasal | Improved cognition and reduced Aβ pathology. | [70] |
| Parkinson’s disease | |||
| C57BL + MPTP | 7.5 mg/kg i.p. | Reduced the loss of TH+ neurons. | [71] |
| α-Synuclein overexpression | 14 ppm | Improved forepaw stepping, rotarod, and pole test performances. | [73] |
| C57BL/6 + MPTP | 7.5 mg/kg i.p. | Reduction in inflammatory cytokines. | [159] |
| C57BL/6 + MPTP | 3 mg/kg i.p. | TH+ neurons increased and improvement in behavioral measurements of gait. | [72] |
| C57BL/6J + 6-OHDA | 50 mg/kg i.p. | Depression- and anxiety-like behavior eliminated. | [160] |
| Huntington’s disease | |||
| HD-N171-N82Q | 20 mg/kg i.p. | Enhances performance of mice on grip, rotarod, wire walking, and tremors tests. | [74] |
| Neurovascular diseases | |||
| LDLR−/−-fed high-fat diet | 14 ppm | CBF and brain vascular density improved. | [51] |
| LDLR−/−-fed high-fat diet | 14 ppm | Prevented blood brain barrier breakdown. | [158] |
| Brain injury (traumatic brain injury and drug and surgical induced) | |||
| Mice-THC | 1 mg/kg i.p. | Abrogated the amnesic-like effects of delta9-tetrahydrocannabinol (THC). | [161] |
| C57BL/6-TBI | 10 mg/kg i.p. | Reduced neural stem cell proliferation induced by controlled cortical impact. | [162] |
| C57BL/6-surgical | 5 mg/kg i.p. | Cognition improved in postoperative cognitive dysfunction. | [163] |
| Kunming-sepsis | 1, 5, 10 mg/kg i.p. | Rescued learning and memory deficits. | [164] |
| C57BL/6-isoflurane | 1 mg/kg/day i.p. | Cognition improved in isoflurane-induced cognitive impairment. | [165] |
| Neurodevelopmental disorders (autism, epilepsy, seizures, etc.) | |||
| Tsc2+/− | 1 mg/kg i.p. | Rescues synaptic plasticity and behavioral deficits in this autism model. | [81] |
| Tsc1 mutants | Not given | Prevented autistic-like behaviors. | [82] |
| Tsc1+/− | 6 mg/kg i.p. | Reduction in anxiety and depression. | [83] |
| Tsc1fl/fl X GFP-Cre | 6 mg/kg/day i.p. | Increased neuronal migration and spine density in an autism model. | [84] |
| Disc1−/− | 20 mg/kg i.p. | Reversed cognitive and affective deficits in model of schizophrenia/depression. | [166] |
| Sprague Dawley rats | 6 mg/kg i.p. | Improved spatial learning and memory in pilocarpine-induced epilepticus | [167] |
| Cognition and aging | |||
| C57BL6/129svj | 14 ppm | Cognition improved in old (18 months) mice | [78] |
| C57BL/6J | 14 ppm | Cognition improved in 8- and 25-month-old mice | [77] |
|
C57BL/6JRj F344BNF1 rats |
14 ppm 42 ppm (5 months) and then 14 ppm (10 months) |
Cognition improved in 11- and 20-month-old mice Improved cognition, neurovascular uncoupling, and cerebral perfusion in 35-month-old rats |
[79] [80] |
*Used the rapalog, temsirolimus