Abstract：
:Prepulse inhibition (PPI) of acoustic startle reflex is a measure of sensorimotor gating that may reflect the biological processes underlying gaiting impairments in schizophrenia. Although PPI is clinically useful, why PPI is inhibited in schizophrenia is largely unknown. Prepulse inhibition is mediated by M2-like muscarinic acetylcholine receptor on neurons in the caudal pontine reticular nucleus (PnC), activation of this receptor induces Gαi dissociation, and inhibits adenylyl cyclase, resulting in the inhibition of the neurons. On the other hand, the symptoms of schizophrenia are mainly linked to hyperactive dopaminergic activity, mediated by dopamine D2-like receptor. Interestingly, D2-like receptor also uses Gαi. This means that both M2-like acetylcholine receptor and D2-like dopamine receptor use same Gαi-protein, competitively. Thus, chronic over-activation of D2-like receptor observed in schizophrenia may disrupt normal M2-like acetylcholine receptor functions due to their shared coupling to Gαi-proteins, i.e. by reducing the amount of Gαi-protein available for M2-like acetylcholine receptors, resulting in the impairment of PPI.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Sato Kdoi
10.1016/j.mehy.2020.109901subject
Has Abstractpub_date
2020-10-01 00:00:00pages
109901eissn
0306-9877issn
1532-2777pii
S0306-9877(20)30968-3journal_volume
143pub_type
杂志文章abstract：:Diabetes is a global public health challenge that imposes heavy burdens on communities and individuals. Metformin, the first-line medication for diabetes, has the superiority of reducing risk of macrovascular diseases, all-cause mortality and even possibly cancers. Recent observational studies, however, have demonstra...
journal_title：Medical hypotheses
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