2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
April 2nd, 2025
Version: 1
Wake Forest University School of Medicine
neuroscience
biorxiv

A mutation in the transmembrane domain of Adenylate cyclase 3 impairs enzymatic function to cause sex-specific depression- and anxiety-like behaviors and food seeking in a rat model

Fitzpatrick, M. K.Open in Google Scholar•Dyson, C.Open in Google Scholar•Beeson, A.Open in Google Scholar•Adrian, L.Open in Google Scholar•Marrs, G.Open in Google Scholar•Grzybowski, M.Open in Google Scholar•Klotz, J.Open in Google Scholar•Geurts, A. M.Open in Google Scholar•Chen, R.Open in Google Scholar•Weiner, J. L.Open in Google Scholaret al.

We have previously demonstrated that a transmembrane domain mutation in Adenylate cyclase 3 (Adcy3) causes increased adiposity and negative emotion-like behaviors in a rat model. We set out to replicate and expand upon our previous study by conducting comprehensive behavioral testing, and we also investigated the molecular changes that result from this mutation. Rats with a mutation in the second transmembrane helix of ADCY3 (Adcy3mut/mut) and wild-type rats were fed a high-fat diet for 12 weeks. We measured body weight, body composition, and depression-like and anxiety-like behaviors using the following tests: sucrose splash test, sucrose preference test, forced swim test, open field test, elevated plus maze, successive alleys test, and novelty-suppressed feeding. We also measured serum leptin levels, hypothalamic cyclic AMP (cAMP) production, and membrane fraction ADCY3 content. Adcy3mut/mut male and female rats had increased adiposity. Adcy3mut/mut males showed increased despair- and anxiety-like behaviors, food seeking, and higher leptin levels relative to wild-type males. Adcy3mut/mut females showed only mildly increased anxiety-like behaviors relative to wild-type females. Adcy3mut/mut rats of both sexes had decreased cAMP production in the hypothalamus, with no changes in ADCY3 content in the membrane fraction. We conclude that the transmembrane domain of ADCY3 plays a critical role regulating adiposity and behavior, as well as cAMP production. There were key differences between males and females for the observed phenotypes. This study supports the idea that Adcy3 contributes to emotion-like behaviors and potentially mental health disorders, and that the transmembrane domain of ADCY3 is important for protein function.

Similar Papers

biorxiv
Thu Apr 03 2025
Aging reduces excitatory bandwidth, alters spectral tuning curve diversity, and reduces sideband inhibition in L2/3 of primary auditory cortex
Presbycusis, or age-related hearing loss, is caused by changes in both the peripheral and the central auditory system. Many of the peripheral structures that degrade with age have been identified and characterized, but there is still a dearth of information pertaining to what changes occur in the aging central auditory pathway that are independent of peripheral degradation. The primary auditory co...
Maximov, K.
•
O. Kanold, P.
biorxiv
Thu Apr 03 2025
A Kv2 inhibitor combination reveals native neuronal conductances consistent with Kv2/KvS heteromers
KvS proteins are voltage-gated potassium channel subunits that form functional channels when assembled into heteromers with Kv2.1 (KCNB1) or Kv2.2 (KCNB2). Mammals have 10 KvS subunits: Kv5.1 (KCNF1), Kv6.1 (KCNG1), Kv6.2 (KCNG2), Kv6.3 (KCNG3), Kv6.4 (KCNG4), Kv8.1 (KCNV1), Kv8.2 (KCNV2), Kv9.1 (KCNS1), Kv9.2 (KCNS2), and Kv9.3 (KCNS3). Electrically excitable cells broadly express channels contai...
Stewart, R. G.
•
Marquis, M. J.
•
Jo, S.
•
Harris, B.
...•
Sack, J. T.
biorxiv
Thu Apr 03 2025
The extended language network: Language selective brain areas whose contributions to language remain to be discovered
Although language neuroscience has largely focused on core left frontal and temporal brain areas and their right-hemisphere homotopes, numerous other areas - cortical, subcortical, and cerebellar - have been implicated in linguistic processing. However, these areas\' contributions to language remain unclear given that the evidence for their recruitment comes from diverse paradigms, many of which c...
Wolna, A.
•
Wright, A.
•
Lipkin, B.
•
Fedorenko, E.
biorxiv
Thu Apr 03 2025
Common and distinct neural mechanisms of aversive and appetitive pain-related learning
Appetitive and aversive conditioning are both fundamental to adaptive behaviour, yet there remains limited understanding of how they differ on the behavioural and neural level. We investigated the two processes during acquisition and extinction using functional magnetic resonance imaging and behavioural measures. In a within-subject differential conditioning paradigm (preregistration DRKS00027448)...
Li, J.
•
Schmidt, K.
•
Busch, L.
•
Forkmann, K.
...•
Bingel, U.
biorxiv
Thu Apr 03 2025
Mapping the coupling between tract reachability and cortical geometry of the human brain
The study of cortical geometry and connectivity is prevalent in research on the human brain. However, these two aspects of brain structure are usually examined separately, leaving the essential connections between the brain\'s folding patterns and white matter connectivity unexplored. In this study, we aimed to elucidate fundamental links between cortical geometry and white matter tract connectivi...
Li, D.
•
Zalesky, A.
•
Wang, Y.
•
Wang, H.
...•
Fan, L.
biorxiv
Thu Apr 03 2025
Neural Tracking of the Maternal Voice in the Infant Brain
Infants preferentially process familiar social signals, but the neural mechanisms underlying continuous processing of maternal speech remain unclear. Using EEG-based neural encoding models based on temporal response functions, we investigated how 7-month-old infants track maternal vs. unfamiliar speech and whether this affects simultaneous face processing. Infants showed stronger neural tracking o...
Jessen, S.
•
Orf, M.
•
Obleser, J.
biorxiv
Thu Apr 03 2025
Sensory responsivity and its connection to sympathetic activation and deactivation: implications for stress and learning
This study introduces sensory responsivity (SR), which describes individual differences in sensory stimuli response strength and is hypothesised to affect stress responses in students and, in turn, their learning. To investigate this, a scale to assess SR was developed and linked to physiological responses. To this end, electrodermal activity (EDA) and sensory gating data was collected from a labo...
Flo, E. E.
biorxiv
Thu Apr 03 2025
Inferring global exponents in subsampled neural systems
In systems displaying an activity charaterized by avalanches, critical exponents may give informations on the mechanisms underlying the observed behaviour or on the topology of the connections. However, when only a small fraction of the units composing the system are observed and sampled, the measured exponents may differ significantly from the true ones. In this study, using Branching Process and...
Conte, D.
•
de Candia, A.
biorxiv
Thu Apr 03 2025
The Organization of Serotonergic Fibers in the Pacific Angelshark Brain: Neuroanatomical and Supercomputing Analyses
Serotonergic axons (fibers) are a universal feature of all vertebrate brains. They form meshworks, typically quantified with regional density measurements, and appear to support neuroplasticity. The self-organization of this system remains poorly understood, partly because of the strong stochasticity of individual fiber trajectories. In an extension to our previous analyses of the mouse brain, ser...
Janusonis, S.
•
Metzler, R.
•
Vojta, T.
biorxiv
Thu Apr 03 2025
Lower Aperiodic EEG Activity is Associated with Reduced Verbal Fluency Performance Across Adulthood
Age-related cognitive decline associations with human electroencephalography (EEG) have previously focused on periodic activity. However, EEG is primarily made up of non-oscillatory aperiodic activity, which can be characterized with an exponent and offset value. In a secondary analysis of a cohort of 111 healthy participants aged 17-71 years, we examined the associations of the aperiodic exponent...
McKeown, D. J.
•
Roberts, E.
•
Finley, A. J.
•
Kelley, N. J.
...•
Angus, D. J.