THPP-1 PDE10A inhibitor reverses the cognitive deficits and hyperdopaminergic state in a neurodevelopment model of schizophrenia.

Schizophrenia (SCZ) is a complex neuropsychiatric disorder characterized by positive, negative, and cognitive symptoms. The neurodevelopmental methylazoxy-methanol acetate (MAM) rodent model replicates key neurobiological features of SCZ which includes hyperdopaminergic states in the ventral tegmental area (VTA) and cognitive deficits. Typical and atypical antipsychotics are primarily effective in treating the positive symptoms of SCZ but often fall short of addressing cognitive deficits.

The excitatory-inhibitory balance as a target for the development of novel drugs to treat schizophrenia.

The intricate balance between excitation and inhibition (E/I) in the brain plays a crucial role in normative information processing. Dysfunctions in the E/I balance have been implicated in various psychiatric disorders, including schizophrenia (SCZ). In particular, abnormalities in GABAergic signaling, specifically in parvalbumin (PV)-containing interneurons, have been consistently observed in SCZ pathophysiology.

Insights into the Mechanism of Action of Antipsychotic Drugs Derived from Animal Models: Standard of Care versus Novel Targets.

Therapeutic intervention for schizophrenia relies on blockade of dopamine D2 receptors in the associative striatum; however, there is little evidence for baseline overdrive of the dopamine system. Instead, the dopamine system is in a hyper-responsive state due to excessive drive by the hippocampus. This causes more dopamine neurons to be in a spontaneously active, hyper-responsive state.

Mesenchymal stromal cells facilitate resolution of pulmonary fibrosis by miR-29c and miR-129 intercellular transfer.

To date, pulmonary fibrosis remains an unmet medical need. In this study, we evaluated the potency of mesenchymal stromal cell (MSC) secretome components to prevent pulmonary fibrosis development and facilitate fibrosis resolution. Surprisingly, the intratracheal application of extracellular vesicles (MSC-EVs) or the vesicle-depleted secretome fraction (MSC-SF) was not able to prevent lung fibrosis when applied immediately after the injury caused by bleomycin instillation in mice.