Dopamine differently modulates central cholinergic circuits in patients with Alzheimer disease and CADASIL

Abstract

Short-latency afferent inhibition (SAI) technique gives the opportunity to non-invasively test an inhibitory circuit in the human cerebral motor cortex that depends mainly on central cholinergic activity. Important SAI abnormalities have been reported in both patients with Alzheimer disease (AD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a model of "pure" vascular dementia (VD). Interestingly, a normalization of SAI was observed in AD after levo-dopa (L-dopa) administration. We aimed to determine whether the pharmacological manipulation of the dopaminergic system can also interfere with SAI test in CADASIL patients, compared with AD patients and healthy controls. SAI was found to be significantly reduced in both patient groups. L-Dopa significantly increased SAI in the AD patients, while it failed to restore SAI abnormality in CADASIL patients. Therefore, L-dopa-mediated changes on SAI in AD patients seem to be a specific effect. The present study supports the notion that relationship between acetylcholine and dopamine systems may be specifically abnormal in AD. L-Dopa challenge may thus be able to differentiate the patients with AD or a mixed form of dementia from those with "pure" VD.

Vascular Cognitive Impairment through the Looking Glass of Transcranial Magnetic Stimulation

“…Therefore, it has been hypothesized that the cortical hyperexcitability in CADASIL might be caused by cholinergic, GABA-ergic, and glutamatergic neuron dysfunction, supporting the hypothesis of several neurotransmitter system involvement in CADASIL, similar to other forms of dementia [78]. More recently, short-latency afferent inhibition was found to be significantly reduced in both AD and CADASIL patients, although administration of L-3,4-dihydroxyphenylalanine (L-Dopa) was able to significantly increase short-latency afferent inhibition in the AD group only, suggesting that relationship between acetylcholine and dopamine systems may be specifically abnormal in AD [92]. …”

Chemical profiling analysis of Maca using UHPLC-ESI-Orbitrap MS coupled with UHPLC-ESI-QqQ MS and the neuroprotective study on its active ingredients

“…Dopamine was supposed to possess modulatory effect in cholinergic transmission, which played a critical role in modulating cortical cholinergic activity by GABAergic intracortical circuits46. And the dopaminergic system might be dysfunctional in AD, which was possibly generated by the disrupting of the cholinergic system4748. Thus, after the evaluation of Maca on dopamine neuronal loss model in zebrafish by the method of anti-tyrosine hydroxylase (TH) whole-mount immunostaining , the AChE and BuChE inhibition activities of 6 fractions and pure compound were carried out.…”

Update on the Neurobiology of Vascular Cognitive Impairment: From Lab to Clinic

“…Therefore, a total of 46 papers were eventually included in this study ( Figure 1) and the main findings are summarized in Table 1. More in details, 8 studies deal with serum biomarkers [9][10][11][12][13][14][15][16], 10 with cerebrospinal fluid (CSF) [17][18][19][20][21][22][23][24][25][26], 4 with neuroimaging [27][28][29][30], 6 with histopathology [31][32][33][34][35][36], and 14 with transcranial magnetic stimulation (TMS) [37][38][39][40][41][42][43][44][45][46][47][48][49][50]; 4 studies included more than one technique: one studied both serum and CSF markers [51], two both serum and neuroimaging [52,53], and one both CSF and neuroimaging…”