Hippocampal small RNAs from patients with schizophrenia induce specific cognitive and neural phenotypes in mice [human]

Cognitive deficits can appear even before the onset of the first psychotic episode and their severity has been recently associated with altered levels of small RNAs (sRNAs), including microRNAs. Nevertheless, how the dysregulation of sRNAs can lead to cognitive impairments and their role in the onset and pathophysiology of the disorder are still unknown.

In our research, we hypothesized that hippocampal sRNAs generated in patients with schizophrenia could contribute to the impairment of specific cognitive domains that are altered in the disease. Through deep sequencing, we identified novel dysregulated sRNAs (including microRNAs and tRNA derived fragments) in the hippocampus of patients with schizophrenia. Furthermore, when injected in the hippocampus of wild-type mice, animals exhibited an impairment in spatial short-term memory accompanied by a reduction in spine density of CA1 pyramidal neurons.