Social Memory and Social Patterns Alterations in the Absence of STriatal-Enriched Protein Tyrosine Phosphatase

Abstract

STriatal-Enriched protein tyrosine Phosphatase (STEP) is a neural-specific protein that opposes the development of synaptic strengthening and whose levels are altered in several neurodegenerative and psychiatric disorders. Since STEP is expressed in brain regions implicated in social behavior, namely the striatum, the CA2 region of the hippocampus, cortex and amygdala, here we investigated whether social memory and social patterns were altered in STEP knockout (KO) mice. Our data robustly demonstrated that STEP KO mice presented specific social memory impairment as indicated by the three-chamber sociability test, the social discrimination test, the 11-trial habituation/dishabituation social recognition test, and the novel object recognition test (NORT). This affectation was not related to deficiencies in the detection of social olfactory cues, altered sociability or anxiety levels. However, STEP KO mice showed lower exploratory activity, reduced interaction time with an intruder, less dominant behavior and higher immobility time in the tail suspension test than controls, suggesting alterations in motivation. Moreover, the extracellular levels of dopamine (DA), but not serotonin (5-HT), were increased in the dorsal striatum of STEP KO mice. Overall, our results indicate that STEP deficiency disrupts social memory and other social behaviors as well as DA homeostasis in the dorsal striatum.

Regulation of glutamate receptors by striatal‐enriched tyrosine phosphatase 61 (STEP61)

“…There are many studies demonstrating a role for STEP in the regulation of plasticity and behaviour and in neurological disorders. For example, STEP KO mice present specific social memory impairment (Blazquez et al 2018). The first study of high throughput screening for STEP inhibitors reported that benzopentathiepin 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (known as TC-2153) is a potent STEP inhibitor, which forms a reversible covalent bond with the catalytic cysteine in STEP.…”

Dysfunction of striatal MeCP2 is associated with cognitive decline in a mouse model of Alzheimer's disease

“…We presume that the increased binding of MeCP2 in MEF2C and ADAM10 may lead to hippocampal memory deficits in the APP/PS1. In addition, our MeCP2 ChIP-seq analysis also found increased binding of MeCP2 to the STriatal-Enriched Protein Tyrosine Phosphatase ( STEP ), of which its absence triggers disrupted social memory retention and social patterns 61 . Thus, we suggest that increased binding of MeCP2 on the STEP gene may result in abrupt social memory deficits in the early ages of APP/PS1 mice.…”

Food preference acquired by social transmission is altered by the absence of the olfactory marker protein in mice

“…To determine whether Omp null mice have a specific deficit in STFP/food-related odorant recognition rather than an alteration in their general olfactory capacities, we next examined the social discrimination ability displayed by these mice in a resident—intruder paradigm assay ( 41 ; Figures 4F,G ). For that, a resident mouse (R) ( Figure 4F ) socially investigates a first intruder mouse (I1) ( Figure 4F ).…”

“…Social discrimination test, adapted from previously described procedures ( 41 , 61 ), was conducted in a specific behavioral room under standard light-dark cycle. Residents and juvenile intruders (25–40 days old) male and female mice, were tested with an equivalent sex ratio.…”