PMID- 32102370
OWN - NLM
STAT- MEDLINE
DCOM- 20201123
LR  - 20201123
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 4
DP  - 2020 Feb 24
TI  - Neurons, Glia, Extracellular Matrix and Neurovascular Unit: A Systems Biology 
      Approach to the Complexity of Synaptic Plasticity in Health and Disease.
LID - 10.3390/ijms21041539 [doi]
LID - 1539
AB  - The synaptic cleft has been vastly investigated in the last decades, leading to a 
      novel and fascinating model of the functional and structural modifications linked 
      to synaptic transmission and brain processing. The classic neurocentric model 
      encompassing the neuronal pre- and post-synaptic terminals partly explains the 
      fine-tuned plastic modifications under both pathological and physiological 
      circumstances. Recent experimental evidence has incontrovertibly added 
      oligodendrocytes, astrocytes, and microglia as pivotal elements for synapse 
      formation and remodeling (tripartite synapse) in both the developing and adult 
      brain. Moreover, synaptic plasticity and its pathological counterpart 
      (maladaptive plasticity) have shown a deep connection with other molecular 
      elements of the extracellular matrix (ECM), once considered as a mere 
      extracellular structural scaffold altogether with the cellular glue (i.e., glia). 
      The ECM adds another level of complexity to the modern model of the synapse, 
      particularly, for the long-term plasticity and circuit maintenance. This model, 
      called tetrapartite synapse, can be further implemented by including the 
      neurovascular unit (NVU) and the immune system. Although they were considered so 
      far as tightly separated from the central nervous system (CNS) plasticity, at 
      least in physiological conditions, recent evidence endorsed these elements as 
      structural and paramount actors in synaptic plasticity. This scenario is, as far 
      as speculations and evidence have shown, a consistent model for both adaptive and 
      maladaptive plasticity. However, a comprehensive understanding of brain processes 
      and circuitry complexity is still lacking. Here we propose that a better 
      interpretation of the CNS complexity can be granted by a systems biology approach 
      through the construction of predictive molecular models that enable to enlighten 
      the regulatory logic of the complex molecular networks underlying brain function 
      in health and disease, thus opening the way to more effective treatments.
FAU - De Luca, Ciro
AU  - De Luca C
AD  - Laboratory of Morphology of Neuronal Network, Department of Public Medicine, 
      University of Campania "Luigi Vanvitelli", 80138 Napoli, Italy.
FAU - Colangelo, Anna Maria
AU  - Colangelo AM
AD  - Laboratory of Neuroscience "R. Levi-Montalcini", Dept. of Biotechnology and 
      Biosciences, University of Milano-Bicocca, 20126 Milano, Italy.
AD  - SYSBIO Centre of Systems Biology ISBE.ITALY, University of Milano-Bicocca, 20126 
      Milano, Italy.
FAU - Virtuoso, Assunta
AU  - Virtuoso A
AD  - Laboratory of Morphology of Neuronal Network, Department of Public Medicine, 
      University of Campania "Luigi Vanvitelli", 80138 Napoli, Italy.
FAU - Alberghina, Lilia
AU  - Alberghina L
AD  - SYSBIO Centre of Systems Biology ISBE.ITALY, University of Milano-Bicocca, 20126 
      Milano, Italy.
FAU - Papa, Michele
AU  - Papa M
AD  - Laboratory of Morphology of Neuronal Network, Department of Public Medicine, 
      University of Campania "Luigi Vanvitelli", 80138 Napoli, Italy.
AD  - SYSBIO Centre of Systems Biology ISBE.ITALY, University of Milano-Bicocca, 20126 
      Milano, Italy.
LA  - eng
GR  - 2017XJ38A4_003/Ministero dell'Istruzione, dell'Universita e della Ricerca/
PT  - Journal Article
PT  - Review
DEP - 20200224
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
SB  - IM
MH  - Animals
MH  - Central Nervous System/physiology
MH  - Epilepsy/physiopathology
MH  - Extracellular Matrix/*physiology
MH  - Humans
MH  - Neuroglia/cytology/*physiology
MH  - *Neuronal Plasticity
MH  - Neurons/cytology/*physiology
MH  - Synapses/*physiology
MH  - Systems Biology/*methods
PMC - PMC7073232
OTO - NOTNLM
OT  - glia, tripartite synapse, synaptic plasticity, neurovascular unit, systems 
      biology
COIS- The authors declare no conflict of interests.
EDAT- 2020/02/28 06:00
MHDA- 2020/11/24 06:00
PMCR- 2020/02/01
CRDT- 2020/02/28 06:00
PHST- 2019/12/31 00:00 [received]
PHST- 2020/02/19 00:00 [revised]
PHST- 2020/02/20 00:00 [accepted]
PHST- 2020/02/28 06:00 [entrez]
PHST- 2020/02/28 06:00 [pubmed]
PHST- 2020/11/24 06:00 [medline]
PHST- 2020/02/01 00:00 [pmc-release]
AID - ijms21041539 [pii]
AID - ijms-21-01539 [pii]
AID - 10.3390/ijms21041539 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Feb 24;21(4):1539. doi: 10.3390/ijms21041539.