TY - CHAP
T1 - Alterations and interactions of subcortical modulatory systems in Alzheimer's disease
AU - Babić Leko, Mirjana
AU - Hof, Patrick R.
AU - Šimić, Goran
N1 - Funding Information:
This work was funded by The Croatian Science Foundation grant IP-2019-04-3584 (“Role of blood-brain barrier, innate immunity, and tau protein oligomerization in the pathogenesis of Alzheimer's disease”) to GŠ and by the Scientific Centre of Excellence for Basic, Clinical and Translational Neuroscience CoRE-NEURO (“Experimental and clinical research of hypoxic-ischemic damage in perinatal and adult brain”; GA KK01.1.1.01.0007 funded by the European Union through the European Regional Development Fund), and in part by NIH grant P50 AG005138 to PRH.
Publisher Copyright:
© 2021 Elsevier B.V.
PY - 2021/1
Y1 - 2021/1
N2 - The pathogenesis of Alzheimer's disease (AD) is not fully understood. Here we summarize current knowledge on the involvement of the serotonergic, noradrenergic, dopaminergic, cholinergic, and opioid systems in AD, emphasizing the importance of interactions between the serotonergic and the other subcortical modulatory systems during the progression of AD. In physiological conditions, all neurotransmitter systems function in concert and are interdependent at both the neuroanatomical and molecular levels. Through their early involvement in AD, cognitive and behavioral abilities that rely on their interactions also become disrupted. Considering that serotonin (5HT) regulates the release of noradrenaline (NA), dopamine (DA) and acetylcholine (ACh), any alteration in 5HT levels leads to disturbance of NA, DA, and ACh homeostasis in the brain. One of the earliest pathological changes during the prodromal phase of AD is a decrease of serotonergic transmission throughout the brain, with serotonergic receptors being also affected. Additionally, serotonergic and noradrenergic as well as serotonergic and dopaminergic nuclei are reciprocally interconnected. As the serotonergic dorsal raphe nucleus (DRN) is affected by pathological changes early in AD, and the noradrenergic locus coeruleus (LC) and dopaminergic ventral tegmental area (VTA) exhibit AD-related pathological changes, their connectivity also becomes altered in AD. Such disrupted interactions among neurotransmitter systems in AD can be used in the development of multi-target drugs. Some of the potential AD therapeutics (such as ASS234, RS67333, tropisetron) target multiple neurotransmitter systems to achieve the best possible improvement of cognitive and behavioral deficits observed in AD. Here, we review how serotonergic system interacts with other subcortical modulatory systems (noradrenergic, dopaminergic, cholinergic, and opioid systems) during AD.
AB - The pathogenesis of Alzheimer's disease (AD) is not fully understood. Here we summarize current knowledge on the involvement of the serotonergic, noradrenergic, dopaminergic, cholinergic, and opioid systems in AD, emphasizing the importance of interactions between the serotonergic and the other subcortical modulatory systems during the progression of AD. In physiological conditions, all neurotransmitter systems function in concert and are interdependent at both the neuroanatomical and molecular levels. Through their early involvement in AD, cognitive and behavioral abilities that rely on their interactions also become disrupted. Considering that serotonin (5HT) regulates the release of noradrenaline (NA), dopamine (DA) and acetylcholine (ACh), any alteration in 5HT levels leads to disturbance of NA, DA, and ACh homeostasis in the brain. One of the earliest pathological changes during the prodromal phase of AD is a decrease of serotonergic transmission throughout the brain, with serotonergic receptors being also affected. Additionally, serotonergic and noradrenergic as well as serotonergic and dopaminergic nuclei are reciprocally interconnected. As the serotonergic dorsal raphe nucleus (DRN) is affected by pathological changes early in AD, and the noradrenergic locus coeruleus (LC) and dopaminergic ventral tegmental area (VTA) exhibit AD-related pathological changes, their connectivity also becomes altered in AD. Such disrupted interactions among neurotransmitter systems in AD can be used in the development of multi-target drugs. Some of the potential AD therapeutics (such as ASS234, RS67333, tropisetron) target multiple neurotransmitter systems to achieve the best possible improvement of cognitive and behavioral deficits observed in AD. Here, we review how serotonergic system interacts with other subcortical modulatory systems (noradrenergic, dopaminergic, cholinergic, and opioid systems) during AD.
KW - 5-Hydroxytryptamine (serotonin)
KW - Acetylcholine
KW - Alzheimer's disease
KW - Dopamine
KW - Interaction
KW - Noradrenaline
KW - Opioids
UR - http://www.scopus.com/inward/record.url?scp=85099631976&partnerID=8YFLogxK
U2 - 10.1016/bs.pbr.2020.07.016
DO - 10.1016/bs.pbr.2020.07.016
M3 - Chapter
C2 - 33785136
AN - SCOPUS:85099631976
SN - 9780444642585
T3 - Progress in Brain Research
SP - 379
EP - 421
BT - 5-HT Interaction with Other Neurotransmitters
A2 - Di Giovanni, Giuseppe
A2 - Di Giovanni, Giuseppe
A2 - De Deurwaerdere, Philippe
PB - Elsevier B.V.
ER -