Targeting the cannabinoid system to counteract the deleterious effects of stress in Alzheimer’s disease


Ronnie D | Jennifer A | Van Bockstaele | Elisabeth J


Involvement of stress circuits in Alzheimer’s disease neuropathology Postmortem evidence Braak and colleagues have suggested that the LC is amongst the earliest brain regions involved in AD neuropathology (Braak and Del Tredici, 2011b). NE levels in the PFC play a major role in working memory and cognitive function. Moreover, it has been demonstrated that increased glucocorticoid levels induce Aβ deposition and tauopathy within the hypothalamus in a rodent model of AD (Green et al., 2006). Cannabinoid 1 receptors (CB1r) are psychoactive receptors typically found in the brain with some present in the periphery. Abbreviations ACEA, Arachidonyl-2 ′ -chloroethylamide, 11; ACEA action, synthetic CB1r selective agonist, 11; ACTH, adrenocorticotropic hormone, 5; AD, Alzheimer’s Disease, 3; APOE, apolipoprotein E, 3; APP, amyloid precursor protein, 3; APP/PS1, amyloid precursor protein/presenilin 1, 9; APPswe/PS1dE9, amyloid precursor protein/presenilin 1 double transgenic, 9; AR, adrenergic receptor, 5; A β, Amyloid Beta Peptide, 4; BBB, blood brain barrier, 5; BPSD, behavioral and psychological symptoms of dementia, 4; CBD, Cannabidiol, 11; CBD action, Negative Allosteric Modulator of CB1, 11; cdk-5, cyclin-dependent kinase 5, 16; CeA, central nucleus of the amygdala, 6; CRF, corticotropin releasing factor, 5; CRF-OE, overexpress CRF, 7; CRFR1, CRF receptor 1, 7; DSM-5, Diagnostic and Statistical Manual of Mental Disorders 5, 3; eCBRIs, endocannabinoid reuptake inhibitors, 11; ELISA, enzyme linked immunoassay, 7; ERK1/2, extracellular signal-regulated kinase, 16; GFAP, glial fibrillary acidic protein, 7; GSK3 β, glycogen synthase kinase 3 beta, 5; HPA, hypothalamic-pituitary-adrenal, 3; IL-mPFC, infralimbic mPFC, 6; JNK, c-Jun N- terminal kinase, 16; JWH-133, Synthetic CB2r Selective Agonist, 11; LC, locus coeruleus, 6; LOAD, late onset AD, 3; MAPK, mitogen-activated protein kinases, 16; MMSE, Mini Mental State Examination, 8; NE, norepinephrine, 6; NFT, neurofibrillary tangles, 5; NIA-AA, National Institute of Aging/Alzheimer’s Association, 3; NINCDS-ADRDA, National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association, 3; NO, nitric oxide, 5; PET, positron emission tomography, 4; PFC, prefrontal cortex, 6; PL-mPFC, prelimbic medial PFC, 6; PSEN1, presenilin 1, 3; PSEN2, presenilin 2, 3; PVN, paraventricular nucleus of the hypothalamus, 5; VSMCs, vascular smooth muscle cells, 5; WIN 55-212, 2, Non-selective (CB1 and CB2) Cannabinoid Agonist, 11; β -APPs, β -amyloid precursor proteins, 8.

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