Effects of Npas4 deficiency on anxiety, depression-like, cognition and sociability behaviour

Jaehne, Emily J.; Klarić, Thomas Stephen; Koblar, Simon; Baune, Bernhard T.; Lewis, Martin

doi:10.1016/j.bbr.2014.12.044

Cited by 45 publications

(42 citation statements)

References 42 publications

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“…However, it is unclear whether down-regulation of Npas4 is involved in the maladaptive changes that lead to stress-induced disorders or the stress adaption response that reinstates homeostasis. Results from studies using Npas4 knockout animals [32, 36], although not entirely consistent with each other, generally appear to support the latter idea, although mice deficient in Npas4 exhibited impaired adult neurogenesis in the hippocampal subventricular zone, consistent with the former possibility [32]. Further studies are needed to investigate Npas4’s function in stress in a region-specific manner, as it might play different roles in different brain regions.…”

Section: Behaviorally-induced Npas4 Expressionmentioning

confidence: 81%

Npas4: Linking Neuronal Activity to Memory

Sun

Lin

2016

Trends in Neurosciences

162

146

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Immediate early genes (IEGs) are rapidly activated after sensory and behavioral experience and are believed to be critical for converting experience into long-term memory. Neuronal PAS domain protein 4 (Npas4), a recently discovered IEG, has several characteristics that make it likely to be a particularly important molecular link between neuronal activity and memory: it is among the most rapidly induced IEGs, is expressed only in neurons, and is selectively induced by neuronal activity. By orchestrating distinct activity-dependent gene programs in different neuronal populations, Npas4 affects synaptic connections in excitatory and inhibitory neurons, neural circuit plasticity and memory formation. It may also be involved in circuit homeostasis through negative feedback and psychiatric disorders. We summarize these findings and discusses their implications.

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Section: Behaviorally-induced Npas4 Expressionmentioning

confidence: 81%

Npas4: Linking Neuronal Activity to Memory

Sun

Lin

2016

Trends in Neurosciences

162

146

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“…However, behavioral changes in the open‐field in PNS HET mice were only minor and further studies, using other behavioral assays (eg, elevated‐plus maze or light‐dark box) should be used to confirm our observation. Furthermore, Npas4 deficiency has not been associated with increased anxiety‐like behavior in past studies using male mice, while PNS has been shown to induce anxiety‐like behavior in both sexes in adulthood . The PFC is a known contributor to the regulation of anxiety and environmentally induced loss of prefrontal PV during development has been associated with increased anxiety‐like behaviors (ie, References ).…”

Section: Discussionmentioning

confidence: 99%

“…Past studies indicate that Npas4 deficiency alone does not produce social recognition deficits in male rodents, 17,37 while studies on the effects of PNS alone have produced mixed results in the emergence of social memory deficits in adulthood. 38,39 Here we found that a combination of Npas4 deficiency and exposure to PNS leads to a deficit in social recognition.…”

Section: Discussionmentioning

confidence: 99%

Npas4 deficiency and prenatal stress interact to affect social recognition in mice

Heslin

Coutellier

2018

Genes Brain and Behavior

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Neurodevelopmental disorders such as autism spectrum disorders and schizophrenia have an expansive array of reported genetic and environmental contributing factors. However, none of these factors alone can account for a substantial proportion of cases of either disorder. Instead, many gene-by-environment interactions are responsible for neurodevelopmental disturbances that lead to these disorders. The current experiment used heterozygous knock-out mice to examine a potential interaction between 2 factors commonly linked to neurodevelopmental disorders and cognitive deficit: imbalanced excitatory/inhibitory signaling in the cortex and prenatal stress (PNS) exposure. Both of these factors have been linked to disrupt GABAergic signaling in the prefrontal cortex (PFC), a common feature of neurodevelopmental disorders. The neuronal PAS domain protein 4 (Npas4) gene is instrumental in regulation of the excitatory/inhibitory balance in the cortex and hippocampus in response to activation. Npas4 heterozygous and wild-type male and female mice were exposed to either PNS or standard gestation, then evaluated during adulthood in social and anxiety behavioral measures. The combination of PNS and Npas4 deficiency in male mice impaired social recognition. This behavioral deficit was associated with decreased parvalbumin and cFos protein expression in the infralimbic region of the PFC following social stimulation in Npas4 heterozygous males. In contrast, females displayed fewer behavioral effects and molecular changes in PFC in response to PNS and decreased Npas4.

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“…Two “stranger” enclosures, diameter 9 cm, height 10 cm, were placed in the two outer chambers. The test consisted of three phases, each 10 min in duration, which were conducted immediately after one another (8, 39). Stranger mice were adolescent 5-HT 1A heterozygous mice of the same sex as the test mouse.…”

Section: Methodsmentioning

confidence: 99%

Investigating the Role of Serotonin in Methamphetamine Psychosis: Unaltered Behavioral Effects of Chronic Methamphetamine in 5-HT1A Knockout Mice

et al. 2017

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Methamphetamine (Meth) is a widely abused stimulant drug, but this abuse is associated with an increased risk of developing psychosis. In addition to its well-known action on brain dopamine, Meth also affects serotonergic (5-HT) neurons. The aim of this study was to investigate this role in mice, which lack one of the main serotonin receptors, the 5-HT1A receptor, which has been implicated in both schizophrenia and Meth-induced psychosis. Male and female wild-type or 5-HT1A knockout (KO) mice received daily treatment with increasing doses of methamphetamine from 6 to 9 weeks of age (1–4 mg/kg/day twice a day). At least 2 weeks after the last injection, the mice underwent a battery of behavioral tests focusing on psychosis-related behaviors, including Meth-induced hyperactivity, prepulse inhibition (PPI), social interaction, elevated plus maze (EPM), and Y-maze. Meth pretreatment resulted in significantly increased hyperlocomotion in response to an acute Meth challenge, but this effect was independent of genotype. Chronic Meth treatment resulted in decreased levels of anxiety in the EPM in both sexes, as well as increased startle responses in female mice only, again independent of genotype. 5-HT1A KO mice showed an increased locomotor response to acute Meth in both sexes, as well as increased PPI and decreased startle responses in female mice only, independent of Meth pretreatment. In conclusion, the effects of chronic Meth appear unaffected by the absence of the 5-HT1A receptor. These results do not support a role of the 5-HT1A receptor in Meth-induced psychosis.

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Effects of Npas4 deficiency on anxiety, depression-like, cognition and sociability behaviour

Cited by 45 publications

References 42 publications

Npas4: Linking Neuronal Activity to Memory

Npas4: Linking Neuronal Activity to Memory

Npas4 deficiency and prenatal stress interact to affect social recognition in mice

Investigating the Role of Serotonin in Methamphetamine Psychosis: Unaltered Behavioral Effects of Chronic Methamphetamine in 5-HT1A Knockout Mice

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