Table 2 Mechanisms of neuronal damage, and possible beneficial effects of 5-HT₇ receptors agonism

Excitotoxicity

Activation of MAPK/ERK and PI3/Akt/GSK3b protects against glutamate-induced damage

Decreased expression of NR2B and NR1 subunits of NMDA glutamate receptors

Increased expression of superoxide dismutase and glutathione

Jiang et al. (2000); Pi et al. (2004); Li et al. (2005)

Vasefi et al. (2013a)

Yuksel et al. (2019)

Oxidative stress

No study evaluated effect in the CNS

In a sepsis-induced lung injury, 5-HT₇ receptor agonism decreased ROS burden

5-HT₇ antagonism decreased oxidative burden in bleomycin-induced pulmonary fibrosis

5-HT₇ activation enhances microsome stability towards oxidative metabolism (Lacivita et al., 2016a)

ERK and Akt protect PC12 cells from oxidative damage

Cadirci et al. (2013)

Tawfik and Makary (2017)

Lacivita et al. (2016a)

Ong et al. (2016)

Apoptosis

5-HT₇ receptor agonism reduces apoptosis in the streptozotocin-induced AD model

Hashemi-Firouzi et al. (2017)

Long term depression/ potentiation impairment

5-HT₇ KO mice display LTP impairment

5-HT₇ agonism reduces mGluR-dependent LTD

Roberts et al. (2004)

Costa et al. (2012)

Synaptic impairment

5-HT₇ agonism increases dendritic density and synaptogenesis in the cortical and striatal forebrain

5-HT₇ agonism induces dendritic sprouting and neurite enlargement

Speranza et al. (2013, 2015, 2017)

Kvachnina et al. (2005); Canese et al. (2015)

Neurotrophin depletion

5-HT₇ agonism increases PDGF-β

5-HT₇ agonism increases the expression and affinity of trk-B

Vasefi et al. (2013b)

Samarajeewa et al. (2014)