Null mutation in P4h-tm leads to decreased fear and anxiety and increased social behavior in mice.

In this study, we first investigated the expression pattern of P4H-TM in the mouse brain and found a remarkably selective abundance in brains areas that are involved in social behaviors and anxiety including amygdala, lateral septum and bed nucleus of stria terminalis. Next, we performed behavioral assays in P4h-tm-/- mice to investigate a possible phenotype associated to these brain areas. In locomotor activity tests, we found that P4h-tm-/- mice were significantly more active than their wild-type (WT) littermate mice, and habituation to test environment did not abolish this effect. Instead, spatial learning and memory seemed normal in P4h-tm-/- mice as assessed by Morris swim task. In several tests assessing anxiety and fear responses, P4h-tm-/- mice showed distinct courageousness, and they presented increased interaction towards fellow mice in social behavior tests. Most strikingly, P4h-tm-/- mice practically lacked behavioral despair response, a surrogate marker of depression, in forced swim and tail suspension tests. Instead, mutant mice of all other Hif-p4h isoforms lacked such a behavioral phenotype. In summary, this study presents a remarkable anatomy-physiology association between the brain expression of P4H-TM and the behavioral phenotype in P4h-tm-/- mice. Future studies will reveal whether P4H-TM may serve as a novel target for anti-depressant and anti-anxiety pharmacotherapy. PMID: 31029587 [PubMed - as supplied by publisher]
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research