Differential involvement of 5-HT(1B/1D) and 5-HT6 receptors in cognitive and non-cognitive symptoms in Alzheimer's disease.
Growing evidence suggests that a compromised serotonergic system plays an important role in the pathophysiology of Alzheimer's disease (AD). We assessed the expression of 5-HT(1B/1D) and 5-HT(6) receptors and cholinacetyltransferase (ChAT) activity in post-mortem frontal and temporal cortex from AD patients who had been prospectively assessed for cognitive function using the Mini-Mental State Examination (MMSE) and behavioral changes using the Present Behavioral Examination (PBE). 5-HT(1B/1D) and 5-HT(6) receptor densities were significantly reduced in both cortical areas. 5-HT(1B/1D) receptor density was correlated to MMSE decline in the frontal cortex, supporting its implication in memory impairment. The best predictor for lowered 5-HT(6) receptor density in the temporal cortex was the PBE measure of overactivity. The 5-HT(6)/ChAT ratio was related to aggression both in the frontal and temporal cortex. Therefore, antagonists acting at 5-HT(6) receptors could be useful in the treatment of non-cognitive symptoms associated to AD.
Garcia-Alloza
M
M
Department of Pharmacology, School of Medicine, University of Navarra, Pamplona, Spain.
Hirst
W D
WD
Chen
C P L-H
CP
Lasheras
B
B
Francis
P T
PT
Ramírez
M J
MJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D001549:Benzamides / Q000493:pharmacokinetics / Q000627:therapeutic use; D001665:Binding Sites; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007554:Isotopes / Q000493:pharmacokinetics; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D010879:Piperazines / Q000493:pharmacokinetics; D011725:Pyridines / Q000493:pharmacokinetics / Q000627:therapeutic use; D044302:Receptor, Serotonin, 5-HT1B / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000493:pharmacokinetics / Q000627:therapeutic use; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics; D013223:Statistics as Topic; D013449:Sulfonamides / Q000493:pharmacokinetics; D013702:Temporal Lobe / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology
D001549:Benzamides; D007554:Isotopes; C107225:N-(4-methoxy-3-(4-methylpiperazin-1-yl)phenyl)-3-methyl-4-(4-pyridyl)benzamide; D010879:Piperazines; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; C418570:SB 258585; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; C097216:serotonin 6 receptor; D002795:Choline O-Acetyltransferase