Loss of SST and PV positive interneurons in the ventral hippocampus results in anxiety-like behavior in 5xFAD mice

Li, Hongzhu; Zhao, Jiaying; Lai, Lanfeng; Xia, Yucen; Wan, Chaofan; Shen, Wei; Liang, Jiaming; Chen, Yongjun; Xu, Nenggui

doi:10.1016/j.neurobiolaging.2022.05.013

Cited by 15 publications

(19 citation statements)

References 80 publications

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“…The results demonstrated that dexmedetomidine can inhibit the release of stress hormones; however, this effect alone does not fully explain its anxiolytic effects. CRH PVN neurons potentially directly modulate neurons closely associated with anxiety, such as those in the amygdala, [40][41][42] medial prefrontal cortex, 43,44 and ventral hippocampus, 45,46 transmitting signals that reduce stress through neural pathways, thus contributing to the anxiolytic effects of dexmedetomidine. This potential mechanism requires further investigation in the future.…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Inhibits Paraventricular Corticotropin-releasing Hormone Neurons that Attenuate Acute Stress-induced Anxiety-like Behavior in Mice

Qiu,

Wang,

Rao

et al. 2024

Anesthesiology

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Background Dexmedetomidine has repeatedly shown to improve anxiety but the precise neural mechanisms underlying this effect remain incompletely understood. Here, we aim to explore the role of corticotropin-releasing hormone-producing hypothalamic paraventricular (CRHPVN) neurons in mediating the anxiolytic effects of dexmedetomidine. Methods A social defeat stress mouse model was employed to evaluate the anxiolytic effects induced by dexmedetomidine through the elevated plus-maze, open-field test, and measurement of serum stress hormone levels. In vivo Ca2+ signal fibre photometry and ex vivo patch-clamp recordings were utilized to determine the excitability of CRHPVN neurons and investigate the specific mechanism involved. CRHPVN neuron modulation was achieved through chemogenetic activation or inhibition. Results Compared with saline, dexmedetomidine (40 µg/kg) alleviated anxiety-like behaviors. Additionally, dexmedetomidine reduced CRHPVN neuronal excitability. Chemogenetic activation of CRHPVN neurons decreased the time spent in the open arms of the elevated plus-maze and in the central area of the open-field test. Conversely, chemogenetic inhibition of CRHPVN neurons had the opposite effect. Moreover, the suppressive impact of dexmedetomidine on CRHPVN neurons was attenuated by the α2 receptor antagonist yohimbine. Conclusions Our results indicate that the anxiety-like effects of dexmedetomidine are mediated via α2 adrenergic receptor-triggered inhibition of CRHPVN neuronal excitability in the hypothalamus.

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Section: Discussionmentioning

confidence: 99%

Dexmedetomidine Inhibits Paraventricular Corticotropin-releasing Hormone Neurons that Attenuate Acute Stress-induced Anxiety-like Behavior in Mice

Qiu,

Wang,

Rao

et al. 2024

Anesthesiology

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“…2k). Compared to WT mice, young adult PS cDKO mice showed signi cant decreases in the powers of theta (3-8 Hz), beta (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), and gamma (30-100 Hz) oscillations in vCA1, which suggests diminished activity of interneurons (Fig. 2l).…”

Section: Anxiety-like Behaviors In Young Adult Ps Cdko Micementioning

confidence: 94%

“…PV + interneurons target almost all nearby PNs to control the timing of spikes in PNs and HPC network activity 12 . Dysfunction of PV + interneurons has been linked to anxiety and AD 13,14 .…”

Section: Introductionmentioning

confidence: 99%

Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice

Yang²,

Zhao³

et al. 2023

Preprint

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Anxiety, as an early manifestation of Alzheimer’s disease (AD), plays a significant role in the initial stages of cognitive decline and has a negative impact on the progression of the disease. However, the specific pathological mechanisms underlying anxiety in early stage of AD remain largely unknown. In this study, we investigated anxiety-like behaviors in presenilin 1/2 conditional double knockout (PS cDKO) mice, which are commonly used to study AD. To characterize anxiety-like behaviors, we conducted a battery of behavioral tests on young adult PS cDKO mice. Additionally, we performed electrophysiological recordings to examine the balance of excitatory and inhibitory activity in the synapses of pyramidal neurons and the neural network oscillations in the ventral hippocampus (vHPC) CA1 (vCA1) region of PS cDKO mice displaying anxiety-like behaviors. Our findings revealed a shift in the normal excitatory/inhibitory (E/I) balance and neural oscillations in the vCA1 region of PS cDKO mice with anxiety-like behaviors. Furthermore, we observed that parvalbumin-positive (PV+) interneurons, which play a crucial role in regulating the balance of excitatory and inhibitory activity, exhibited hypoexcitability in the vCA1 of PS cDKO mice. Mechanistically, we identified increased levels of Kv1.1, a voltage-gated potassium channel, in the vCA1 PV+ interneurons of PS cDKO mice. Genetically or pharmacologically, when we inhibited Kv1.1 in the vCA1 region, the hypoexcitability of PV+ interneurons was reversed and anxiety-like behaviors in PS cDKO mice were rescued. Therefore, we propose that the increased Kv1.1 levels in vCA1 PV+ interneurons reduce the excitability of PV+ interneurons, ensuing disrupted E/I balance of pyramidal neuron synapses causes anxiety in young adult PS cDKO mice. These findings provide new insights into the mechanisms underlying early AD-related anxiety-like behaviors.

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“…Stress due to maternal separation (MS) in rodents leads to anxiety-like behaviours in adulthood as characterized by heightened fear, avoidance, and stress sensitivity (Banqueri et al, 2017;Lundberg et al, 2020;Balouek et al, 2023). The ventral hippocampus, a key brain area affected by MS (Dimatelis et al, 2014;Marais et al, 2009), has been shown to regulate emotions (Jimenez et al, 2018;H. Li et al, 2022;McNaughton, 1997).…”

Section: Introductionmentioning

confidence: 99%

Gas5 regulates early life stress-induced anxiety and spatial memory

Banerjee,

Sultana,

Banerjee

2023

Preprint

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The early life stress (ES) of maternal separation (MS) evokes anxiety and memory deficits. Emerging studies have shown that MS-induced gene expression in the hippocampus is operated at the level of transcription. However, the involvement of non-coding RNAs in MS-induced behavioural deficits is poorly understood. Here, we have explored the role of synapse-enriched long non-coding RNAs (lncRNAs) in anxiety and memory upon MS. We observed that MS led to an enhancement of expression of the lncRNA Gas5 (Growth Arrest Specific-5) in the hippocampus; accompanied by increased levels of anxiety and deficits in spatial memory. The knockdown of Gas5 in early life could reduce anxiety and partially rescue the spatial memory deficit of maternally separated adult mice following MS. Gene Ontology analysis revealed that Gas5 exerts its function by regulating RNA metabolism and translation. Our study highlights the importance of MS-regulated lncRNA in anxiety and spatial memory.SIGNIFICANCE STATEMENTThe mechanism of early-life stress-induced gene expression and its implications in associated behavioural deficits are poorly resolved. The study fills this void by identifying lncRNA as a regulatory factor linked with early life stress of maternal separation. This study demonstrates that the reversal of Gas5 expression, a synapse-enriched lncRNA, enables the partial rescue of anxiety and memory deficits. Our study highlights an RNA-based approach to alleviate the adverse effects of early life stress.

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Loss of SST and PV positive interneurons in the ventral hippocampus results in anxiety-like behavior in 5xFAD mice

Cited by 15 publications

References 80 publications

Dexmedetomidine Inhibits Paraventricular Corticotropin-releasing Hormone Neurons that Attenuate Acute Stress-induced Anxiety-like Behavior in Mice

Dexmedetomidine Inhibits Paraventricular Corticotropin-releasing Hormone Neurons that Attenuate Acute Stress-induced Anxiety-like Behavior in Mice

Kv1.1 channel dysfunction in parvalbumin-positive interneurons contributes to anxiety-like behaviors in young adult presenilin 1/2 conditional double knockout mice

Gas5 regulates early life stress-induced anxiety and spatial memory

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